Sample records for adult female cynomolgus

  1. Sertraline inhibits increases in body fat and carbohydrate dysregulation in adult female cynomolgus monkeys

    PubMed Central

    Silverstein-Metzler, Marnie G.; Shively, Carol A.; Clarkson, Thomas B.; Appt, Susan E.; Carr, J.Jeffrey; Kritchevsky, Stephen B.; Jones, Sara R.; Register, Thomas C.

    2017-01-01

    Selective serotonin reuptake inhibitor (SSRI) antidepressants are widely prescribed for depression and other disorders. SSRIs have become one of the most commonly used drugs in the United States, particularly by women. Acute effects on body composition and carbohydrate metabolism have been reported, but little is known regarding the effects of chronic SSRI use. We evaluated the effects of chronic administration of a commonly prescribed SSRI, sertraline HCl, on body weight and composition, fat distribution, carbohydrate metabolism, as well as activity, in adult female depressed and nondepressed cynomolgus monkeys (Macaca fascicularis; n = 42) using a placebo-controlled, longitudinal, randomized study design. Phenotypes were evaluated prior to and after 18 months of oral sertraline (20 mg/kg) or placebo. Over the 18 month treatment period, the placebo group experienced increases in body weight, body fat (visceral and subcutaneous) fasting insulin concentrations, and homeostasis model assessment of insulin resistance scores (HOMA-IR). Sertraline treatment prevented increases in body weight, fat, insulin, and HOMA-IR (all p < 0.05), without significantly altering activity levels. Sertraline treatment altered adiponectin in an unusual way — reducing circulating adiponectin in depressed monkeys without affecting fat mass or body weight. Deleterious effects on adiponectin, a potentially insulin-sensitizing and atheroprotective protein, may result in adverse effects on cardiovascular health despite otherwise beneficial effects on body composition and carbohydrate metabolism. PMID:26939086

  2. Sexual dimorphism of sulcal length asymmetry in the cerebrum of adult cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Imai, Noritaka; Sawada, Kazuhiko; Fukunishi, Katsuhiro; Sakata-Haga, Hiromi; Fukui, Yoshihiro

    2011-12-01

    The present study aimed to quantitatively clarify the gross anatomical asymmetry and sexual dimorphism of the cerebral hemispheres of cynomolgus monkeys. While the fronto-occipital length of the right and left cerebral hemispheres was not different between sexes, a statistically significant rightward asymmetry was detected in the cerebral width at the perisylvian region in females, but not in males (narrower width of the left side in the females). An asymmetry quotient of the sulcal lengths revealed a rightward asymmetry in the inferior occipital sulcus and a leftward asymmetry in the central and intraparietal sulci in both sexes. However, the laterality of the lengths of other sulci was different for males and females. The arcuate sulcus was directed rightward in males but there was no rightward bias in females. Interestingly, the principle sulcus and lateral fissure were left-lateralized in the males, but right-lateralized in the females. The results suggest that lateralization patterns are regionally and sexually different in the cerebrum of cynomolgus monkeys. The present results provide a reference for quantitatively evaluating the normality of the cerebral cortical morphology in cynomolgus monkeys. © 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.

  3. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ren, Zhenhua; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing; Department of Anatomy, Anhui Medical University, Hefei, 230032

    2011-12-10

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristicsmore » of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: Black-Right-Pointing-Pointer Spontaneous transformation of cynomolgus monkey MSCs in vitro. Black-Right-Pointing-Pointer Transformed mesenchymal cells lack multipotency. Black-Right-Pointing-Pointer Transformed mesenchymal cells are highly tumorigenic. Black-Right-Pointing-Pointer Transformed mesenchymal cells do not have the characteristics of cancer stem cells.« less

  4. Evaluation of Infrared Thermometry in Cynomolgus Macaques (Macaca fascicularis)

    PubMed Central

    Laffins, Michael M; Mellal, Nacera; Almlie, Cynthia L; Regalia, Douglas E

    2017-01-01

    Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry techniques with the objective of demonstrating the diagnostic equivalence of the infrared device with other approaches. Infrared thermometer readings are instantaneous and require no contact with the animal. Body temperature data were obtained from 205 (137 male, 68 female) cynomolgus macaques under ketamine (10 mg/kg IM) sedation over a 3-mo period during scheduled physical examinations. Infrared measurements were taken 5 cm from the chest and inguinal areas. We evaluated 10 (9 functional devices) sedated cynomolgus macaques (5 male, 5 female) implanted with telemetry units in a muscular pouch between the internal and external abdominal oblique muscles. We determined that the mean body temperature acquired by using telemetry did not differ from either the mean of inguinal and chest infrared measurements but did differ from the mean of temperature obtained rectally. In addition, the mean rectal temperature differed from the mean of the inguinal reading but not the mean of the chest temperature. The results confirm our hypothesis that the infrared thermometer can be used to replace standard rectal thermometry. PMID:28905720

  5. Evaluation of Infrared Thermometry in Cynomolgus Macaques (Macaca fascicularis).

    PubMed

    Laffins, Michael M; Mellal, Nacera; Almlie, Cynthia L; Regalia, Douglas E

    2017-01-01

    Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry techniques with the objective of demonstrating the diagnostic equivalence of the infrared device with other approaches. Infrared thermometer readings are instantaneous and require no contact with the animal. Body temperature data were obtained from 205 (137 male, 68 female) cynomolgus macaques under ketamine (10 mg/kg IM) sedation over a 3-mo period during scheduled physical examinations. Infrared measurements were taken 5 cm from the chest and inguinal areas. We evaluated 10 (9 functional devices) sedated cynomolgus macaques (5 male, 5 female) implanted with telemetry units in a muscular pouch between the internal and external abdominal oblique muscles. We determined that the mean body temperature acquired by using telemetry did not differ from either the mean of inguinal and chest infrared measurements but did differ from the mean of temperature obtained rectally. In addition, the mean rectal temperature differed from the mean of the inguinal reading but not the mean of the chest temperature. The results confirm our hypothesis that the infrared thermometer can be used to replace standard rectal thermometry.

  6. Effects of prior cocaine self-administration on cognitive performance in female cynomolgus monkeys.

    PubMed

    Kromrey, Sarah A; Gould, Robert W; Nader, Michael A; Czoty, Paul W

    2015-06-01

    Cocaine use has been associated with cognitive impairments that may contribute to poor treatment outcomes. However, the degree to which these deficits extend into periods of abstinence has not been completely elucidated. This study tested whether prior experience self-administering cocaine affected acquisition of two cognitive tasks in 16 adult female cynomolgus monkeys. Seven monkeys had previously self-administered cocaine but had not had access to cocaine for 2 months at the start of this study. After monkeys were trained to respond on a touchscreen, associative learning and behavioral flexibility were assessed using a stimulus discrimination (SD) and reversal (SDR) task from the CANTAB battery. Performance on this task was monitored over the subsequent 3 months. Additionally, working memory was assessed with a delayed match-to-sample (DMS) task. Cocaine-naïve monkeys required fewer total trials and made fewer errors and omissions before acquiring the SD and SDR tasks compared with monkeys who had previously self-administered cocaine; two monkeys in the latter group did not acquire the task. However, this cognitive impairment dissipated over several months of exposure to the task. The number of sessions for touch training and delays required to establish a performance-based curve on the DMS task did not differ between groups. Results suggest that cocaine exposure can impair the ability to learn a novel task requiring behavioral inhibition and flexibility, even after an extended period of abstinence. However, this deficit did not extend to maintenance of the task or to acquisition of a working memory task.

  7. First description of the surgical anatomy of the cynomolgus monkey liver.

    PubMed

    Vons, Corinne; Beaudoin, Sylvie; Helmy, Nada; Dagher, Ibrahim; Weber, Anne; Franco, Dominique

    2009-05-01

    No detailed description of nonhuman primate liver anatomy has been reported and little is known about the similarity between such livers and human liver. The cynomolgus monkey (Macaca fascicularis) was used to establish a preclinical model of genetically modified hepatocytes auto transplantation. Here, we report information gleaned from careful observation and notes obtained from 59 female cynomolgus monkeys undergoing 44 anatomical hepatic resections, 12 main portal vein division dissections and selective branch ligations, and 46 portographies. Additionally, three anatomical liver dissections after total resection at autopsy were performed and served to confirm peroperative observations and for photography to provide illustrations. Our results indicate that the cynomolgus monkey liver has four lobes: the median (the largest), the right and left lateral, and the caudate lobes. In 60% (N=20) of individuals the portal bifurcates into right and left portal veins, in the remaining 40% (N=14) the portal vein trifurcates into right anterior, right posterior, and left portal veins. The anatomy and branching pattern of the hepatic artery and bile ducts closely follow those of the portal branches. Functionally, the cynomolgus monkey liver can be divided into eight independent segments. Thus, we report the first detailed description of the hepatic and portal surgical anatomy of the cynomolgus monkey. The cynomolgus monkey liver is more similar to the human liver than are livers of any small or large nonprimate mammals that have been described. (c) 2009 Wiley-Liss, Inc.

  8. Behavioral and neurobiological characteristics influencing social hierarchy formation in female cynomolgus monkeys.

    PubMed

    Riddick, N V; Czoty, P W; Gage, H D; Kaplan, J R; Nader, S H; Icenhower, M; Pierre, P J; Bennett, A; Garg, P K; Garg, S; Nader, M A

    2009-02-18

    Socially housed monkeys have been used as a model to study human diseases. The present study examined behavioral, physiological and neurochemical measures as predictors of social rank in 16 experimentally naïve, individually housed female cynomolgus monkeys (Macaca fascicularis). The two behavioral measures examined were novel object reactivity (NOR), as determined by latency to touch an opaque acrylic box placed in the home cage, and locomotor activity assessed in a novel open-field apparatus. Serum cortisol concentrations were evaluated three times per week for four consecutive weeks, and stress reactivity was assessed on one occasion by evaluating the cortisol response to adrenocorticotropic hormone (ACTH) following dexamethasone suppression. Measures of serotonin (5-HT) function included whole blood 5-HT (WBS) concentrations, cerebrospinal fluid (CSF) concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) and brain 5-HT transporter (SERT) availability obtained using positron emission tomography (PET). After baseline measures were obtained, monkeys were assigned to four social groups of four monkeys per group. The two measures that correlated with eventual social rank were CSF 5-HIAA concentrations, which were significantly higher in the animals who eventually became subordinate, and latency to touch the novel object, which was significantly lower in eventual subordinate monkeys. Measures of 5-HT function did not change as a consequence of social rank. These data suggest that levels of central 5-HIAA and measures of novel object reactivity may be trait markers that influence eventual social rank in female macaques.

  9. Establishment of an immortal cynomolgus macaque fibroblast cell line for propagation of cynomolgus macaque cytomegalovirus (CyCMV).

    PubMed

    Ambagala, Aruna P; Marsh, Angie K; Chan, Jacqueline K; Mason, Rosemarie; Pilon, Richard; Fournier, Jocelyn; Sandstrom, Paul; Willer, David O; MacDonald, Kelly S

    2013-05-01

    Cynomolgus macaques are widely used as an animal model in biomedical research. We have established an immortalized cynomolgus macaque fibroblast cell line (MSF-T) by transducing primary dermal fibroblasts isolated from a 13-year-old male cynomolgus macaque with a retrovirus vector expressing human telomerase reverse transcriptase (hTERT). The MSF-T cells showed increased telomerase enzyme activity and reached over 200 in vitro passages compared to the non-transduced dermal fibroblasts, which reached senescence after 43 passages. The MSF-T cell line is free of mycoplasma contamination and is permissive to the newly identified cynomolgus macaque cytomegalovirus (CyCMV). CyCMV productively infects MSF-T cells and induces down-regulation of MHC class I expression. The MSF-T cell line will be extremely useful for the propagation of CyCMV and other cynomolgus herspesviruses in host-derived fibroblast cells, allowing for the retention of host-specific viral genes. Moreover, this cell line will be beneficial for many in vitro experiments related to this animal model.

  10. Naturally occurring menopause in cynomolgus monkeys: changes in hormone, lipid, and carbohydrate measures with hormonal status.

    PubMed

    Kavanagh, Kylie; Koudy Williams, J; Wagner, Janice D

    2005-08-01

    Naturally occurring post-menopausal (PM) female cynomolgus monkeys (Macaca fascicularis) were identified. Their sex hormone profile was characterized and compared with younger pre-menopausal females before and after ovariectomy (OVX). PM females had lower estrogens and increased follicle-stimulating hormone (FSH) concentrations. Two PM females had diabetes mellitus and elevated androgens (androstenodione and dihydroepiandrosterone sulfate). Non-diabetic PM females were given parenteral E(2) which normalized FSH, and caused improvements in body weight, plasma lipids and lipoprotein cholesterol. Androgens remained lower with E(2) treatment. OVX induced comparable increases in FSH seen with the PM monkeys, however they had lower body weights, and had higher estrone and androstenodione concentrations. Natural menopause occurs in cynomolgus monkeys and hormone changes with OVX are similar however, differences in sex hormones that can relate to body mass and age may be important. E(2) treatment restored estrogen levels and induced improvements in the lipid profile of PM females.

  11. Perspectives on using a multiplex human kidney safety biomarker panel to detect cisplatin-induced tubular toxicity in male and female Cynomolgus monkeys.

    PubMed

    Chen, Yafei; Dale Thurman, J; Kinter, Lewis B; Bialecki, Russell; Eric McDuffie, J

    2017-12-01

    Multiplex biomarker panel assays would enable early de-risking of discovery compound related kidney safety liabilities. The objective of this study was to evaluate the usefulness of the Myriad RBM Human KidneyMAP (Multi-Analyte Profile)® v.1.0 panel to detect experimental nephrotoxicity in Cynomolgus monkeys following a single intravenous administration of cisplatin (2.5mg/kg). Urine samples were collected at baseline on day -2; at approximately 4hr post-dose on day 1; and on days 4, 9, 15 and/or 20. Blood samples were collected at predose on day -2; at 4hr post-dose on day 1; and on days 2, 5, 10 and/or 21. Changes in toxicokinetic and biochemistry parameters in plasma, qualitative/quantitative urinalysis parameters, and urinary kidney safety biomarkers were assessed. Kidney tissues were collected on days 2, 5, 10 and 21 for routine microscopy. Cisplatin-induced tubular alterations were characterized by acute and progressive cortical tubular degeneration/necrosis, regeneration, tubular dilation and proteinaceous cast in the absence of statistically significant changes in traditional plasma biochemistry and urinalysis parameters. When normalized to urinary creatinine, cisplatin-induced significant increases in urinary levels of kidney injury molecule 1 (females on day 4), increases in calbindin D28k (males and females on day 4), decreases in Tamm-Horsfall glycoprotein (males on days 1, 4 and 9), and increases in clusterin (females and males on days 15 and 20, respectively), when compared to concurrent controls. This study revealed the usefulness of the Human KidneyMAP® multiplex panel when measuring changes in urine-based biomarkers to reliably detect cisplatin-induced acute/progressive cortical tubular injury in male and female Cynomolgus monkeys. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Postnatal change in sulcal length asymmetry in cerebrum of cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Sakamoto, Kazuhito; Sawada, Kazuhiko; Fukunishi, Katsuhiro; Noritaka, Imai; Sakata-Haga, Hiromi; Yoshihiro, Fukui

    2014-02-01

    The purpose of this study was to determine the timing of the onset of adult-type sulcal length asymmetry during postnatal development of the male cynomolgus monkey cerebrum. The monkey brain has already reached adult size by 3 months of age, although the body weight only represents 1/8 of the adult body weight by that time. The fronto-occipital length and the cerebral width also reached adult levels by that postnatal age with no left/right bias. Consistently, lengths of the major primary sulci reached adult levels by 3 months of age, and then decreased slightly in sexually mature monkeys (4-6.5 years of age). Asymmetry quotient analysis showed that sulcal length asymmetry patterns gradually changed during postnatal development. The male adult pattern of sulcal length asymmetry was acquired after 24 months of age. In particular, age-dependent rightward lateralization of the arcuate sulcal length was revealed during cerebral maturation by three-way ANOVA. The results suggest that the regional difference in cerebral maturation from adolescence to young adulthood modifies the sulcal morphology with characteristic asymmetric patterns in male cynomolgus monkeys. Copyright © 2013 Wiley Periodicals, Inc.

  13. Vaginal Stone in a Cynomolgus Macaque (Macaca fascicularis).

    PubMed

    Colagross-Schouten, Angela M; Canfield, Don R

    2015-12-01

    A 20-y-old female cynomolgus macaque (Macaca fascicularis) housed in an indoor primate facility presented for poor appetite and acute weakness after several years of no adverse health events. Physical examination revealed a firm, ovoid mass in the caudal abdomen. Further evaluation revealed the mass to be a vaginal calculus composed of calcium carbonate, apatite, and struvite. To our knowledge, this case is the first reported description of a vaginal stone in an NHP.

  14. Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.

    PubMed

    Perigard, Christopher J; Parrula, M Cecilia M; Larkin, Matthew H; Gleason, Carol R

    2016-06-01

    In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss. © 2016 American Society for Veterinary Clinical Pathology.

  15. Histopathology of Incidental Findings in Cynomolgus Monkeys (Macaca Fascicularis) Used in Toxicity Studies

    PubMed Central

    Sato, Junko; Doi, Takuya; Kanno, Takeshi; Wako, Yumi; Tsuchitani, Minoru; Narama, Isao

    2012-01-01

    The purpose of our publication is to widely communicate pictures of spontaneous findings occurring in cynomolgus monkeys. Focal lymphoplasmacytic infiltration is commonly seen in the general organs. The frequency and severity of these lesions may be influenced by the administration of drugs with an effect on the immune system. Lymphoplasmacytic infiltration in the lamina propria of the stomach is also frequently seen in cynomolgus monkeys, and it is caused mainly by a Helicobacter pylori infection. Various degrees of brown pigments are observed in various organs, and it is possible to distinguish the material of the pigments by its morphological features and site. A focal/segmental glomerular lesion is occasionally seen in a section of the kidney, and the minimal lesion has no influence on the urinalysis. We showed the common glomerular lesions in HE-stained sections, as well as in PAM- or PAS-stained sections, for understanding the details. Young and pubertal monkeys are usually used in toxicity studies; therefore, understanding various maturation stages of the genital system is important. In particular, the female genital system needs to be understood in the morphology, because their cyclic changes are different from other laboratory animals. Thus, we present the normal features of the cyclic changes of the female genital organs. Furthermore, we provide more information on spontaneous findings in cynomolgus monkeys for exact diagnoses in toxicity studies. PMID:22481861

  16. Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques

    PubMed Central

    Li, Hongzhao; Nykoluk, Mikaela; Li, Lin; Liu, Lewis R.; Omange, Robert W.; Soule, Geoff; Schroeder, Lukas T.; Toledo, Nikki; Kashem, Mohammad Abul; Correia-Pinto, Jorge F.; Liang, Binhua; Schultz-Darken, Nancy; Alonso, Maria J.; Whitney, James B.; Plummer, Francis A.

    2017-01-01

    Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline) antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10), respectively (PCS peptides), and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research. PMID:28982126

  17. Stress in cynomolgus monkeys (Macaca fascicularis) subjected to long-distance transport and simulated transport housing conditions.

    PubMed

    Fernström, A L; Sutian, W; Royo, F; Westlund, K; Nilsson, T; Carlsson, H-E; Paramastri, Y; Pamungkas, J; Sajuthi, D; Schapiro, S J; Hau, J

    2008-11-01

    The stress associated with transportation of non-human primates used in scientific research is an important but almost unexplored part of laboratory animal husbandry. The procedures and routines concerning transport are not only important for the animals' physical health but also for their mental health as well. The transport stress in cynomolgus monkeys (Macaca fascicularis) was studied in two experiments. In Experiment 1, 25 adult female cynomolgus monkeys were divided into five groups of five animals each that received different diets during the transport phase of the experiment. All animals were transported in conventional single animal transport cages with no visual or tactile contact with conspecifics. The animals were transported by lorry for 24 h at ambient temperatures ranging between 20 degrees C and 35 degrees C. Urine produced before, during and after transport was collected and analysed for cortisol by enzyme-linked immunosorbent assay (ELISA). All monkeys exhibited a significant increase in cortisol excretion per time unit during the transport and on the first day following transport.Although anecdotal reports concerning diet during transport, including the provision of fruits and/or a tranquiliser, was thought likely to influence stress responses, these were not corrobated by the present study. In Experiment 2, behavioural data were collected from 18 cynomolgus macaques before and after transfer from group cages to either single or pair housing, and also before and after a simulated transport, in which the animals were housed in transport cages. The single housed monkeys were confined to single transport cages and the pair housed monkeys were kept in their pairs in double size cages. Both pair housed and singly housed monkeys showed clear behavioural signs of stress soon after their transfer out of their group cages.However, stress-associated behaviours were more prevalent in singly housed animals than in pair housed animals, and these behaviours

  18. Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques.

    PubMed

    DeBo, Ryne J; Register, Thomas C; Caudell, David L; Sempowski, Gregory D; Dugan, Gregory; Gray, Shauna; Owzar, Kouros; Jiang, Chen; Bourland, J Daniel; Chao, Nelson J; Cline, J Mark

    2015-06-01

    The threat of radiation exposure requires a mechanistic understanding of radiation-induced immune injury and recovery. The study objective was to evaluate responses to ionizing radiation in ovariectomized (surgically post-menopausal) female cynomolgus macaques. Animals received a single total-body irradiation (TBI) exposure at doses of 0, 2 or 5 Gy with scheduled necropsies at 5 days, 8 weeks and 24 weeks post-exposure. Blood and lymphoid tissues were evaluated for morphologic, cellular, and molecular responses. Irradiated animals developed symptoms of acute hematopoietic syndrome, and reductions in thymus weight, thymopoiesis, and bone marrow cellularity. Acute, transient increases in plasma monocyte chemoattractant protein 1 (MCP-1) were observed in 5 Gy animals along with dose-dependent alterations in messenger ribonucleic acid (mRNA) signatures in thymus, spleen, and lymph node. Expression of T cell markers was lower in thymus and spleen, while expression of macrophage marker CD68 (cluster of differentiation 68) was relatively elevated in lymphoid tissues from irradiated animals. Ovariectomized female macaques exposed to moderate doses of radiation experienced increased morbidity, including acute, dose-dependent alterations in systemic and tissue-specific biomarkers, and increased macrophage/T cell ratios. The effects on mortality exceeded expectations based on previous studies in males, warranting further investigation.

  19. Thymus development in Macaca fascicularis (Cynomolgus monkey): an approach for toxicology and embryology.

    PubMed

    Buse, Eberhard; Habermann, Gunnar; Vogel, Friedhelm

    2006-05-01

    Thymus development was studied in the cynomolgus monkey from day 35 of gestation (gd 35) to the stage of advanced involution in a 21-year-old monkey. Special emphasis was placed on thymus cell generation and cellular pattern formation. At gd 35, the epithelial bud of the thymus was visible in a sagittal position at the level of the thoracic aperture. At gd 50, first lymphocyte-like cells and few Human Leukocyte Antigen-D Region (HLA-DR) immunoreactive cells appeared. The cortico-medullary differentiation, Hassall's body precursors and faint immunoreactivity for T-lymphocytes (CD 3-positive) were detected from gd 60 onwards. First macrophages (CD 68 positive) were apparent at day 70, first CD 20 immunoreactive cells (B-lymphocyte-like cells) at gd 85, and natural killer cells (M1014 immunoreactive) at gd 100. At gd 100 all evaluated cell populations present in the adult cynomolgus monkey thymus were in place, whereas no B- and T-cell precursors or (CD 34 and CD 117, respectively) dendritic cells (CD 35 positive cells) were present. All these immunopositive cells persisted, partly with changing distribution patterns, until the advanced age of 21 years with the exception of natural killer cells, which were present only until adult ages (evaluation at 4-7 years). The rationale of this study was to analyse thymic development in the cynomolgus monkey and to evaluate the relevance of the development of thymus in non-human primate as a model for corresponding human targeted toxicological research.

  20. [Uterine autologous transplantation in cynomolgus monkeys: a preliminary report of 6 case].

    PubMed

    Wang, Yifeng; Zhu, Ying; Yu, Ping; Chen, Gaowen; Cai, Baota; Zhang, Zhengguang; Liu, Na; Lü, Xiaogang; Xiong, Juxiang; Zhong, Lijuan; Rao, Junhua

    2014-12-23

    To evaluate the surgical feasibility of uterine autologous transplantation in female cynomolgus monkeys and explore the effect of microsurgical technique. From May 2011 to March 2014, 6 female cynomolgus monkeys, aged 7 to 12 years, were randomly divided into 2 surgical groups. In group A, gross surgeries were performed with naked eyes. In group B, uterine re-transplantation was performed under 10-time-magnifying microscopy. Anatomical data and operative durations were recorded and analyzed. Viable uterine tissue and vascular patency were observed on trans-abdominal ultrasonography and second-look laparotomy after 3 months. The average uterus retrieval time, average vascular anastomotic time, average perfusion time and average total operative time of group B were 88.7, 147.3 and 320.0 min versus 123.7, 180.7 and 393.7 min in group A. The average perfusion durations were 35.0 and 27.3 min. And there was no inter-group difference. A total of 12 successful vascular procedures (including 6 internal iliac arteries and 6 uterine-ovary veins) of vascular anastomosis were recorded in group B versus 4 cases (including 1 artery and 3 veins) in group A (vein, P > 0.05; artery, P < 0.05). In group A, there was only 1 successful operation but uterus turned necrotic after 4 weeks. In group B, the surgical success rate was 100%. However one animal died due to intestinal obstruction. And in another 2 animals, viable uterine tissue and vascular patency were observed on trans-abdominal ultrasonography and second-look laparotomy. Two survivors resumed cyclicity at days 17 and 50 respectively as a sign of re-established uterine function. This study has demonstrated the feasibility of uterus transplantation by vascular anastomosis in cynomolgus monkeys. And assistance of microsurgical technique can significantly improve the success rate of arterial anastomosis during uterus transplantation.

  1. Survey of prevalence of overweight body condition in laboratory-housed cynomolgus macaques (Macaca fascicularis).

    PubMed

    Bauer, Sharon A; Leslie, Ken E; Pearl, David L; Fournier, Jocelyn; Turner, Patricia V

    2010-07-01

    Excessive weight gain has been reported to occur in captive cynomolgus macaques with little to no change in diet. Overweight body condition can result in development of hyperglycemia and type 2 diabetes and should be avoided. The purpose of this survey was to assess the prevalence of overweight cynomolgus macaques in North American research facilities, including breeding colonies and short-term and long-term facilities, and to describe current methods used to assess body condition. The survey consisted of 51 questions covering animal population demographics, body weight and body condition scoring, feeding, and behavior. Voluntary participants included veterinarians and animal care managers. Respondents from 13 facilities completed the survey, and information was collected on 17,500 cynomolgus macaques. The majority of surveyed facilities housed juvenile and young adult macaques. The reported prevalence of overweight (greater than 10% of ideal body weight) animals ranged between 0% and 20% and reportedly was more frequent in animals younger than 10 y. Most facilities had weight reduction strategies in place. Despite these programs, a significant proportion of animals were reported as being overweight. The results of this survey demonstrate that most North American facilities housing cynomolgus macaques recognize the importance of tracking body condition regularly. However, implementing effective weight reduction programs may be difficult in captive housing environments. Because of the potential for adverse health effects, facilities should have a means of regularly tracking body weight as well as an action plan for managing overweight animals.

  2. Formation of tamoxifen-DNA adducts in multiple organs of adult female cynomolgus monkeys dosed with tamoxifen for 30 days.

    PubMed

    Schild, Laura J; Divi, Rao L; Beland, Frederick A; Churchwell, Mona I; Doerge, Daniel R; Gamboa da Costa, Gonçalo; Marques, M Matilde; Poirier, Miriam C

    2003-09-15

    The use of the antiestrogen tamoxifen (TAM) is associated with an increase in endometrial cancer. TAM-induced endometrial carcinogenesis may proceed through a genotoxin-mediated pathway, although the detection of endometrial TAM-DNA adducts in exposed women is still controversial. In this study, a monkey model has been used to investigate the question of TAM-DNA adduct formation in primates. Two methods have been used to determine TAM-DNA adducts: a TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), using an antiserum that has specificity for (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-desmethyl-TAM) and electrospray ionization tandem mass spectrometry (ES-MS/MS) coupled with on-line sample preparation and high-performance liquid chromatography (HPLC). Mature (19 year old) cynomolgus monkeys were given either vehicle control (n = 1) or TAM (n = 3) twice daily for a total dose of 2 mg of TAM/kg body weight (bw)/day for 30 days by naso-gastric intubation. Tissues were harvested, and DNA was isolated from uterus, ovary, liver, brain cortex, and kidney. By TAM-DNA CIA, values for uterine TAM-DNA adducts in two monkeys were 0.9 and 1.7 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts in the same animals were 0.4 and 0.5 adducts/10(8) nucleotides. Liver, brain cortex, and kidney DNA samples from the three exposed monkeys had TAM-DNA levels of 2.1-4.2 adducts/10(8) nucleotides, 0.4-5.0 adducts/10(8) nucleotides, and 0.7-2.1 adducts/10(8) nucleotides, respectively. By HPLC-ES-MS/MS, the levels of TAM-DNA adducts detected in all tissues were comparable with those observed by TAM-DNA CIA. Thus, values for uterine TAM-DNA adducts ranged from 0.5 to 1.4 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts, measurable in two monkeys, were 0.2 and 0.3 adducts/10(8) nucleotides. Liver DNA contained the highest TAM-DNA adduct levels (7.0-11.1 adducts/10(8) nucleotides

  3. Gamma-hydroxybutyric acid in male and female cynomolgus monkeys trained to discriminate 1.0 or 2.0 g/kg ethanol.

    PubMed

    Helms, Christa M; Rogers, Laura S M; Grant, Kathleen A

    2008-07-01

    Gamma-hydroxybutyric acid has been proposed as a pharmacotherapy for alcoholism in part based on similar discriminative stimulus effects as ethanol. To date, drug discrimination studies with gamma-hydroxybutyric acid and ethanol have exclusively used rodents or pigeons as subjects. To evaluate possible differences between species, sex, and route of administration, this study investigated the substitution of gamma-hydroxybutyric acid (intragastrically or intramuscularly) for ethanol 30 or 60 min after administration in male (n=6) and female (n=7) cynomolgus monkeys trained to discriminate 1.0 and 2.0 g/kg ethanol. At least one dose of gamma-hydroxybutyric acid completely or partially substituted for ethanol in three of the 13 monkeys tested, with each case occurring in female monkeys. Ethanol-appropriate responding did not increase with gamma-hydroxybutyric acid dose. Monkeys were more sensitive to the response rate decreasing effects of gamma-hydroxybutyric acid administered intramuscularly compared with intragastrically. The lack of gamma-hydroxybutyric acid substitution for ethanol suggests that these drugs have different receptor bases for discrimination. Furthermore, the data do not strongly support shared discriminative stimulus effects as the rationale for gamma-hydroxybutyric acid pharmacotherapy for alcoholism.

  4. Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques

    PubMed Central

    Campbell, Kevin J.; Detmer, Ann M.; Karl, Julie A.; Wiseman, Roger W.; Blasky, Alex J.; Hughes, Austin L.; Bimber, Benjamin N.; O’Connor, Shelby L.; O’Connor, David H.

    2009-01-01

    Cynomolgus macaques (Macaca fascicularis) provide increasingly common models for infectious disease research. Several geographically distinct populations of these macaques from Southeast Asia and the Indian Ocean island of Mauritius are available for pathogenesis studies. Though host genetics may profoundly impact results of such studies, similarities and differences between populations are often overlooked. In this study we identified 47 full-length MHC class I nucleotide sequences in 16 cynomolgus macaques of Filipino origin. The majority of MHC class I sequences characterized (39 of 47) were unique to this regional population. However, we discovered eight sequences with perfect identity and six sequences with close similarity to previously defined MHC class I sequences from other macaque populations. We identified two ancestral MHC haplotypes that appear to be shared between Filipino and Mauritian cynomolgus macaques, notably a Mafa-B haplotype that has previously been shown to protect Mauritian cynomolgus macaques against challenge with a simian/human immunodeficiency virus, SHIV89.6P. We also identified a Filipino cynomolgus macaque MHC class I sequence for which the predicted protein sequence differs from Mamu-B*17 by a single amino acid. This is important because Mamu-B*17 is strongly associated with protection against simian immunodeficiency virus (SIV) challenge in Indian rhesus macaques. These findings have implications for the evolutionary history of Filipino cynomolgus macaques as well as for the use of this model in SIV/SHIV research protocols. PMID:19107381

  5. The effect of age on the discriminative stimulus effects of ethanol and its GABA(A) receptor mediation in cynomolgus monkeys.

    PubMed

    Helms, Christa M; Grant, Kathleen A

    2011-08-01

    Excessive alcohol consumption is less common among aged compared to young adults, with aged adults showing greater sensitivity to many behavioral effects of ethanol. This study compared the discriminative stimulus effects of ethanol in young and middle-aged adult cynomolgus monkeys (Macaca fascicularis) and its γ-aminobutyric acid (GABA)(A) receptor mediation. Two male and two female monkeys trained to discriminate ethanol (1.0 g/kg, i.g.; 60-min pre-treatment interval) from water at 5-6 years of age (Grant et al. in Psychopharmacology 152:181-188, 2000) were re-trained in the current study more than a decade later (19.3 ± 1.0 years of age) for a within-subjects comparison. Also, four experimentally naïve middle-aged (mean ± SEM, 17.0 ± 1.5 years of age) female monkeys were trained to discriminate ethanol for between-subjects comparison with published data from young adult naïve monkeys. Two of the naïve middle-aged monkeys attained criterion performance, with weak stimulus control and few discrimination tests, despite greater blood-ethanol concentration 60 min after 1.0 g/kg ethanol in middle-aged compared to young adult female monkeys (Green et al. in Alcohol Clin Exp Res 23:611-616, 1999). The efficacy of the GABA(A) receptor positive modulators pentobarbital, midazolam, allopregnanolone, pregnanolone, and androsterone to substitute for the discriminative stimulus effects of 1.0 g/kg ethanol was maintained from young adulthood to middle age. The data suggest that 1.0 g/kg ethanol is a weak discriminative stimulus in naive middle-aged monkeys. Nevertheless, the GABA(A) receptor mechanisms mediating the discriminative stimulus effects of ethanol, when learned as a young adult, appear stable across one third of the primate lifespan.

  6. Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis).

    PubMed

    Pan, Xueying; Lu, Liang; Zeng, Xiancheng; Chang, Yan; Hua, Xiuguo

    2016-01-01

    To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status.

  7. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

    PubMed Central

    Olson, Erik J.; Lindgren, Bruce R.; Carlson, Cathy S.

    2008-01-01

    The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

  8. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.

    PubMed

    Olson, Erik J; Lindgren, Bruce R; Carlson, Cathy S

    2008-05-01

    The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

  9. Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis)

    PubMed Central

    Pan, Xueying; Lu, Liang; Zeng, Xiancheng; Chang, Yan; Hua, Xiuguo

    2016-01-01

    To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status. PMID:27657707

  10. Characterization of full-length MHC class II sequences in Indonesian and Vietnamese cynomolgus macaques.

    PubMed

    Creager, Hannah M; Becker, Ericka A; Sandman, Kelly K; Karl, Julie A; Lank, Simon M; Bimber, Benjamin N; Wiseman, Roger W; Hughes, Austin L; O'Connor, Shelby L; O'Connor, David H

    2011-09-01

    In recent years, the use of cynomolgus macaques in biomedical research has increased greatly. However, with the exception of the Mauritian population, knowledge of the MHC class II genetics of the species remains limited. Here, using cDNA cloning and Sanger sequencing, we identified 127 full-length MHC class II alleles in a group of 12 Indonesian and 12 Vietnamese cynomolgus macaques. Forty two of these were completely novel to cynomolgus macaques while 61 extended the sequence of previously identified alleles from partial to full length. This more than doubles the number of full-length cynomolgus macaque MHC class II alleles available in GenBank, significantly expanding the allele library for the species and laying the groundwork for future evolutionary and functional studies.

  11. Fetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomide

    EPA Science Inventory

    The present study was performed to determine experimental conditions for thalidomide induction of fetal malformations and to understand the molecular mechanisms underlying thalidomide teratogenicity in cynomolgus monkeys. Cynomolgus monkeys were orally administered (±)-thalidomid...

  12. Efficient production of cynomolgus monkeys with a toolbox of enhanced assisted reproductive technologies

    PubMed Central

    Ma, Yunhan; Li, Jiayu; Wang, Ge; Ke, Qiong; Qiu, Sien; Gao, Liang; Wan, Haifeng; Zhou, Yang; Xiang, Andy Peng; Huang, Qunshan; Feng, Guoping; Zhou, Qi; Yang, Shihua

    2016-01-01

    The efficiency of assisted reproductive technologies (ARTs) in nonhuman primates is low due to no screening criterions for selecting sperm, oocyte, and embryo as well as its surrogate mothers. Here we analyzed 15 pairs of pregnant and non-pregnant cynomolgus monkeys, each pair of which received embryos from one batch of fertilized oocytes, and found ratio of endometrial to myometrial thicknesses in abdominal ultrasonic transverse section of uterus is a reliable indicator for selection of recipients for embryo transfer. We performed 305 ovarian stimulations in 128 female cynomolgus monkeys and found that ovarian stimulation can be performed in a whole year and repeated up to six times in the same monkey without deteriorating fertilization potential of eggs until a poor response to stimulation happened. Fertilization can be efficiently achieved with both conventional and piezo-driven intracytoplasmic sperm injection procedures. In semen collection, semen quality is higher with the penile robe electrical stimulus method compared with the rectal probe method. Moreover, caesarean section is an effective strategy for increasing baby survival rates of multiple pregnancies. These findings provide a practical guidance for the efficient use of ARTs, facilitating their use in genetic engineering of macaque monkeys for basic and translational neuroscience research. PMID:27173128

  13. Limited Susceptibility of Cynomolgus Monkeys (Macaca fascicularis) to Leprosy after Experimental Administration of Mycobacterium leprae

    PubMed Central

    Walsh, Gerald P.; Dela Cruz, Eduardo C.; Abalos, Rodolfo M.; Tan, Esterlina V.; Fajardo, Tranquilino T.; Villahermosa, Laarni G.; Cellona, Roland V.; Balagon, Maria V.; White, Valerie A.; Saunderson, Paul R.; Walsh, Douglas S.

    2012-01-01

    Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis—importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1–19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration. PMID:22855766

  14. The Spiritual Journey: Black Female Adult Learners in Higher Education

    ERIC Educational Resources Information Center

    Jones Tinner, LaShanta Y.

    2013-01-01

    This study explored the experience of Black female adult learners and how spirituality influenced their academic journeys. Research concerning Black female adult learners in higher education is ostensibly partial. These data offered an extended understanding of Black female adult learners' academic experiences, while also investigating common…

  15. Comparison of rectal and infrared thermometry for obtaining body temperature in cynomolgus macaques (Macaca fascicularis).

    PubMed

    Sikoski, P; Banks, M L; Gould, R; Young, R W; Wallace, J M; Nader, M A

    2007-12-01

    It would be clinically advantageous to develop a method of body temperature evaluation in cynomolgus macaques (Macaca fascicularis) that did not require sedation, restraint, surgical manipulation, or expensive equipment. Body temperatures of 51 cynomolgus macaques were taken with rectal thermometry and non-contact infrared thermometry (NIFT) on the shoulder, face, abdomen, and axillary region. Body temperature measurements from NIFT were statistically different (P < 0.0001) from rectal thermometry. In addition, there was greater between- and within-subject variability in values using NIFT. There was no correlation between any sites of the NIFT and rectal thermometry. It was concluded that NIFT was not a valid alternative to rectal thermometry in cynomolgus macaques.

  16. Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome

    PubMed Central

    Lawler, James V; Endy, Timothy P; Hensley, Lisa E; Garrison, Aura; Fritz, Elizabeth A; Lesar, May; Baric, Ralph S; Kulesh, David A; Norwood, David A; Wasieloski, Leonard P; Ulrich, Melanie P; Slezak, Tom R; Vitalis, Elizabeth; Huggins, John W; Jahrling, Peter B; Paragas, Jason

    2006-01-01

    Background The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. Methods and Findings In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. Conclusions SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children. PMID:16605302

  17. Species-Specific Involvement of Integrin αIIbβ3 in a Monoclonal Antibody CH12 Triggers Off-Target Thrombocytopenia in Cynomolgus Monkeys.

    PubMed

    Zhang, Yiting; Sun, Jianhua; Tan, Minjia; Liu, Yongzhen; Li, Qian; Jiang, Hua; Wang, Huamao; Li, Zonghai; Wan, Wei; Jiang, Hualiang; Lu, Henglei; Wang, Bingshun; Ren, Jin; Gong, Likun

    2018-04-07

    CH12 is a novel humanized monoclonal antibody against epidermal growth factor receptor variant III (EGFRvIII) for cancer treatment. Unfortunately, in pre-clinical safety evaluation studies, acute thrombocytopenia was observed after administration of CH12 in cynomolgus monkeys, but not rats. More importantly, in vitro experiments found that CH12 can bind and activate platelets in cynomolgus monkey, but not human peripheral blood samples. Cynomolgus monkey-specific thrombocytopenia has been reported previously; however, the underlying mechanism remains unclear. Here, we first showed that CH12 induced thrombocytopenia in cynomolgus monkeys through off-target platelet binding and activation, resulting in platelet destruction. We subsequently found that integrin αIIbβ3 (which is expressed on platelets) contributed to this off-target toxicity. Furthermore, three-dimensional structural modeling of the αIIbβ3 molecules in cynomolgus monkeys, humans, and rats suggested that an additional unique loop exists in the ligand-binding pocket of the αIIb subunit in cynomolgus monkeys, which may explain why CH12 binds to platelets only in cynomolgus monkeys. Moreover, this study supported the hypothesis that the minor differences between cynomolgus monkeys and humans can confuse human risk assessments and suggests that species differences can help the prediction of human risks and avoid losses in drug development. Copyright © 2018. Published by Elsevier Inc.

  18. Understanding the Burden of Adult Female Acne

    PubMed Central

    Kawata, Ariane K.; Daniels, Selena R.; Yeomans, Karen; Burk, Caroline T.; Callender, Valerie D.

    2014-01-01

    Objective: Typically regarded as an adolescent condition, acne among adult females is also prevalent. Limited data are available on the clinical characteristics and burden of adult female acne. The study objective was to describe clinical characteristics and psychosocial impact of acne in adult women. Design: Cross-sectional, web-based survey. Setting: Data were collected from a diverse sample of United States females. Participants: Women ages 25 to 45 years with facial acne (≥25 visible lesions). Measurements: Outcomes included sociodemographic and clinical characteristics, perceptions, coping behaviors, psychosocial impact of acne (health-related quality of life using acne-specific Quality of Life questionnaire and psychological status using Patient Health Questionnaire), and work/productivity. Results: A total of 208 women completed the survey (mean age 35±6 years), comprising White/Caucasian (51.4%), Black/African American (24.5%), Hispanic/Latino (11.1%), Asian (7.7%), and Other (5.3%). Facial acne presented most prominently on cheeks, chin, and forehead and was characterized by erythema, postinflammatory hyperpigmentation, and scarring. Average age of adult onset was 25±6 years, and one-third (33.7%) were diagnosed with acne as an adult. The majority (80.3%) had 25 to 49 visible facial lesions. Acne was perceived as troublesome and impacted self-confidence. Makeup was frequently used to conceal acne. Facial acne negatively affected health-related quality of life, was associated with mild/moderate symptoms of depression and/or anxiety, and impacted ability to concentrate on work or school. Conclusion: Results highlight the multifaceted impact of acne and provide evidence that adult female acne is under-recognized and burdensome. PMID:24578779

  19. Survival of spectacled eider adult females and ducklings during brood rearing

    USGS Publications Warehouse

    Flint, Paul L.; Grand, James B.

    1997-01-01

    We studied survival of adult female and duckling spectacled eiders (Somateria fischeri) during brood rearing on the Yukon-Kuskokwim Delta, Alaska from 1993 to 1995. Duckling survival to 30 days of age averaged 34% with a 95% confidence interval from 25 to 47%. Half (49%) of radiomarked adult females had lost all their ducklings by 30 days after hatch. Most (74%) duckling mortality occurred in the first 10 days. Adult female survival during the first 30 days of brood rearing was 93 ± 3% (SE). Females died from lead poisoning, as a result of ingesting lead shot, and predation. Mortality of adult females during brood rearing is probably higher than during other times of the year. Low adult female survival during the breeding season may be contributing to the overall population decline of spectacled eiders.

  20. Characterization and phylogenetic epitope mapping of CD38 ADPR cyclase in the cynomolgus macaque

    PubMed Central

    Ferrero, Enza; Orciani, Monia; Vacca, Paola; Ortolan, Erika; Crovella, Sergio; Titti, Fausto; Saccucci, Franca; Malavasi, Fabio

    2004-01-01

    Background The CD38 transmembrane glycoprotein is an ADP-ribosyl cyclase that moonlights as a receptor in cells of the immune system. Both functions are independently implicated in numerous areas related to human health. This study originated from an inherent interest in studying CD38 in the cynomolgus monkey (Macaca fascicularis), a species closely related to humans that also represents a cogent animal model for the biomedical analysis of CD38. Results A cDNA was isolated from cynomolgus macaque peripheral blood leukocytes and is predicted to encode a type II membrane protein of 301 amino acids with 92% identity to human CD38. Both RT-PCR-mediated cDNA cloning and genomic DNA PCR surveying were possible with heterologous human CD38 primers, demonstrating the striking conservation of CD38 in these primates. Transfection of the cDNA coincided with: (i) surface expression of cynomolgus macaque CD38 by immunofluorescence; (ii) detection of ~42 and 84 kDa proteins by Western blot and (iii) the appearance of ecto-enzymatic activity. Monoclonal antibodies were raised against the cynomolgus CD38 ectodomain and were either species-specific or cross-reactive with human CD38, in which case they were directed against a common disulfide-requiring conformational epitope that was mapped to the C-terminal disulfide loop. Conclusion This multi-faceted characterization of CD38 from cynomolgus macaque demonstrates its high genetic and biochemical similarities with human CD38 while the immunological comparison adds new insights into the dominant epitopes of the primate CD38 ectodomain. These results open new prospects for the biomedical and pharmacological investigations of this receptor-enzyme. PMID:15383153

  1. Psychological Sequelae in Adult Females Reporting Childhood Ritualistic Abuse.

    ERIC Educational Resources Information Center

    Lawrence, Kathy J.; And Others

    1995-01-01

    Comparison of 19 adult females reporting childhood ritualistic sexual abuse with 27 adult females reporting sexual abuse without ritualism found that women reporting ritualistic abuse scored significantly higher on measures of childhood sexual and physical abuse severity. Neither posttraumatic stress disorder (PTSD) diagnostic status nor PTSD…

  2. Predicting Human Clearance of OATP substrates using Cynomolgus monkey: In vitro-in vivo scaling of hepatic uptake clearance.

    PubMed

    de Bruyn, Tom; Ufuk, Ayse; Cantrill, Carina; Kosa, Rachel E; Bi, Yi-An; Niosi, Mark; Modi, Sweta; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena Vs; Galetin, Aleksandra; Houston, J Brian

    2018-05-02

    This work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (OATP) transporters. Nine OATP substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. Total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence and presence of the OATP inhibitor rifamycin SV, respectively. Total uptake clearance values in plated hepatocytes ranged over three orders of magnitude in both species with a similar rank order and good agreement in the relative contribution of active transport to total uptake between cynomolgus monkey and human. In vivo hepatic clearance for these nine drugs was determined in cynomolgus monkey after intravenous dosing. Hepatic clearances showed a similar range to human parameters and good predictions from respective hepatocyte parameters (with 2.7 and 3.8-fold bias on average, respectively). The use of cross species empirical scaling factors (based on either dataset average or individual drug scaling factor from cynomolgus monkey data) improved prediction (less bias, better concordance) of human hepatic clearance from human hepatocyte data alone. In vitro intracellular binding in hepatocytes also correlated well between species. It is concluded that the minimal species differences observed for the current dataset between cynomolgus monkey and human hepatocyte uptake, both in vitro and in vivo, support future use of this preclinical model to delineate drug hepatic uptake and enable prediction of human in vivo intrinsic hepatic clearance. The American Society for Pharmacology and Experimental Therapeutics.

  3. Comparative study of the oxidation of propranolol enantiomers in hepatic and small intestinal microsomes from cynomolgus and marmoset monkeys.

    PubMed

    Shimizudani, Takeshi; Nagaoka, Kenjiro; Hanioka, Nobumitsu; Yamano, Shigeru; Narimatsu, Shizuo

    2010-01-05

    Oxidative metabolism of propranolol (PL) enantiomers (R-PL and S-PL) to 4-hydroxypropranolol (4-OH-PL), 5-OH-PL and N-deisopropylpropranolol (NDP) was examined in hepatic microsomes from cynomolgus and marmoset monkeys and in small intestinal microsomes from monkeys and humans. In hepatic microsomes, levels of oxidation activities were similar between the two monkey species, and substrate enantioselectivity (R-PLcynomolgus monkeys, whereas only the formation of NDP was biphasic in marmosets. Inhibition experiments employing human CYP antibodies and chemical inhibitors suggested that mainly CYP2D enzymes and partially CYP1A and 2C enzymes are involved in the oxidation of PL in both monkey liver microsomes. In small intestinal microsomes, activity levels were much higher in cynomolgus monkeys than in marmosets and humans and reversed substrate enantioselectivity (R-PL>S-PL) was seen in the formation of NDP in cynomolgus monkeys and humans and in the formation of 5-OH-PL in marmosets. The formation of the three metabolites in cynomolgus monkeys and the formation of NDP in marmosets were biphasic, while the formation of 4-OH-PL in humans was monophasic. From the inhibition experiments using CYP antibodies, CYP2C9 and 2C19 were thought to be involved as N-deisopropylases and CYP2D6 and 3A4 as 4-hydroxylases in human small intestine. Furthermore, CYP1A, 2C and 3A enzymes could be involved in cynomolgus monkeys and CYP2C and 3A enzymes in marmosets. These results indicate that the oxidative profile of PL in hepatic and small intestinal microsomes differ considerably among cynomolgus monkeys, marmosets and humans.

  4. The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research.

    PubMed

    Kanthaswamy, S; Ng, J; Satkoski Trask, J; George, D A; Kou, A J; Hoffman, L N; Doherty, T B; Houghton, P; Smith, D G

    2013-06-01

    The genetic composition of cynomolgus macaques used in biomedical research is not as well-characterized as that of rhesus macaques. Populations of cynomolgus macaques from Sumatra, Corregidor, Mauritius, Singapore, Cambodia, and Zamboanga were analyzed using 24 STRs. The Sumatran and Cambodian populations exhibited the highest allelic diversity, while the Mauritian population exhibited the lowest. Sumatran cynomolgus macaques were the most genetically similar to all others, consistent with an Indonesian origin of the species. The high diversity among Cambodian animals may result from interbreeding with rhesus macaques. The Philippine and Mauritian samples were the most divergent from other populations, the former due to separation from the Sunda Shelf by deepwater and the latter due to anthropogenic translocation and extreme founder effects. Investigators should verify their research subjects' origin, ancestry, and pedigree to minimize risks to biomedical experimentation from genetic variance stemming from close kinship and mixed ancestry as these can obscure treatment effects. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Emerging Issues in Adult Female Acne

    PubMed Central

    Baldwin, Hillary E.; Cook-Bolden, Fran E.; Eichenfield, Lawrence F.; Friedlander, Sheila F.; Rodriguez, David A.

    2017-01-01

    Acne vulgaris (acne) is a common affliction in adolescence and is a growing problem in adult women. Despite an increasing awareness of acne in the adult female population, there is a lack of good prospective studies assessing the severity, distribution, and differential response to treatment in this group. The long-held dogma that acne in adult women develops on the lower one-third of the face has been recently challenged, and here the authors critically review data from available literature. Moreover, while adult female acne has traditionally been defined as disease in women over age 25, it is the authors’ experience that this group is subdivided into women ages 25 to 44 years, separate from perimenopausal patients, ages 45 years and up. While there is no data specifically comparing these two groups, the authors will review the existing data and provide practical recommendations based on our experience in treating these groups of patients. Finally, while there is a lack of data on this subject, it is the group’s opinion that adherence to medication regimens is likely higher in women than men, which influences therapeutic outcomes. PMID:28210380

  6. Moral dilemmas in females: children are more utilitarian than adults

    PubMed Central

    Bucciarelli, Monica

    2015-01-01

    Influential theories on moral judgments propose that they rely either on emotions or on innate moral principles. In contrast, the mental model theory postulates that moral judgments rely on reasoning, either intuition or deliberation. The theory allows for the possibility that intuitions lead to utilitarian judgments. This paper reports two experiments involving fifth-grade children, adolescents, and adults; the results revealed that children reason intuitively to resolve moral dilemmas in which action and inaction lead to different outcomes. In particular, the results showed female children to be more utilitarian than female adults in resolving classical moral dilemmas: they preferred an action that achieved a good outcome for a greater number of people. Within the mental model theory's framework there is no reason to expect that females and males differ in their ability to reason, but at the moment the results for females cannot be generalized to males who were not properly represented in the adults groups of the two experiments. The result revealing that (female) children are more utilitarian than (female) adults, which is hard to explain via many current theories, was predicted by the mental model theory. PMID:26441722

  7. ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

    PubMed

    Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

    2017-11-01

    A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys.

    PubMed

    Chen, Yongchang; Yu, Juehua; Niu, Yuyu; Qin, Dongdong; Liu, Hailiang; Li, Gang; Hu, Yingzhou; Wang, Jiaojian; Lu, Yi; Kang, Yu; Jiang, Yong; Wu, Kunhua; Li, Siguang; Wei, Jingkuan; He, Jing; Wang, Junbang; Liu, Xiaojing; Luo, Yuping; Si, Chenyang; Bai, Raoxian; Zhang, Kunshan; Liu, Jie; Huang, Shaoyong; Chen, Zhenzhen; Wang, Shuang; Chen, Xiaoying; Bao, Xinhua; Zhang, Qingping; Li, Fuxing; Geng, Rui; Liang, Aibin; Shen, Dinggang; Jiang, Tianzi; Hu, Xintian; Ma, Yuanye; Ji, Weizhi; Sun, Yi Eve

    2017-05-18

    Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure.

    PubMed

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; Almeida, Adilson José de; Pelajo-Machado, Marcelo; Castro, Tatiana Xavier de; Nascimento, Jussara Pereira do; Brown, Kevin E; Pinto, Marcelo Alves

    2016-04-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.

  10. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

    PubMed Central

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; de Almeida, Adilson José; Pelajo-Machado, Marcelo; de Castro, Tatiana Xavier; do Nascimento, Jussara Pereira; Brown, Kevin E; Pinto, Marcelo Alves

    2016-01-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

  11. Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

    DTIC Science & Technology

    2003-12-01

    Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques Evidence that Dendritic Cells Are Early and Sustained Targets of Infection Thomas W...is known about the development of EBOV hemorrhagic fever . In the present study, 21 cynomol- gus monkeys were experimentally infected with EBOV and...Am J Pathol 2003, 163:2347–2370) Among viruses causing hemorrhagic fever (HF), and among emerging infectious diseases with global impact in general

  12. Similar substrate specificity of cynomolgus monkey cytochrome P450 2C19 to reported human P450 2C counterpart enzymes by evaluation of 89 drug clearances.

    PubMed

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-12-01

    Cynomolgus monkeys are used widely in preclinical studies as non-human primate species. The amino acid sequence of cynomolgus monkey cytochrome P450 (P450 or CYP) 2C19 is reportedly highly correlated to that of human CYP2C19 (92%) and CYP2C9 (93%). In the present study, 89 commercially available compounds were screened to find potential substrates for cynomolgus monkey CYP2C19. Of 89 drugs, 34 were metabolically depleted by cynomolgus monkey CYP2C19 with relatively high rates. Among them, 30 compounds have been reported as substrates or inhibitors of, either or both, human CYP2C19 and CYP2C9. Several compounds, including loratadine, showed high selectivity to cynomolgus monkey CYP2C19, and all of these have been reported as human CYP2C19 and/or CYP2C9 substrates. In addition, cynomolgus monkey CYP2C19 formed the same loratadine metabolite as human CYP2C19, descarboethoxyloratadine. These results suggest that cynomolgus monkey CYP2C19 is generally similar to human CYP2C19 and CYP2C9 in its substrate recognition functionality. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Transcriptome sequencing of newly molted adult female cattle ticks, Rhipicephalus microplus: Raw Illumina reads.

    USDA-ARS?s Scientific Manuscript database

    Illumina paired end oligo-dT sequencing technology was used to sequence the transcriptome from newly molted adult females from the cattle tick, Rhipicephalus microplus. These samples include newly molted unfed whole adult females, newly molted whole adult females feeding for 2 hours on a bovine host...

  14. Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

    PubMed Central

    Saul, Louise; Saul, Louise; Josephs, Debra H; Josephs, Debra H; Cutler, Keith; Cutler, Keith; Bradwell, Andrew; Bradwell, Andrew; Karagiannis, Panagiotis; Karagiannis, Panagiotis; Selkirk, Chris; Selkirk, Chris; Gould, Hannah J; Gould, Hannah J; Jones, Paul; Jones, Paul; Spicer, James F; Spicer, James F; Karagiannis, Sophia N; Karagiannis, Sophia N

    2014-01-01

    Background: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.   Methods: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays. Results: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species. Conclusion: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies. PMID:24492303

  15. Ecdysteroid receptors in Drosophila melanogaster adult females

    USDA-ARS?s Scientific Manuscript database

    Ecdysteroid receptors were identified and partially characterized from total cell extracts of whole animals and dissected tissues from Drosophila melanogaster adult females. Binding studies indicated the presence of two ecdysteroid binding components having high affinity and specificity consistent w...

  16. Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa.

    PubMed

    Ikeda, Yasuhiro; Nishiguchi, Koji M; Miya, Fuyuki; Shimozawa, Nobuhiro; Funatsu, Jun; Nakatake, Shunji; Fujiwara, Kohta; Tachibana, Takashi; Murakami, Yusuke; Hisatomi, Toshio; Yoshida, Shigeo; Yasutomi, Yasuhiro; Tsunoda, Tatsuhiko; Nakazawa, Toru; Ishibashi, Tatsuro; Sonoda, Koh-Hei

    2018-02-01

    To accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. In this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (Macaca fascicularis) pedigree. First, screening with fundus photography was performed on 1443 monkeys at the Tsukuba Primate Research Center. Ophthalmic examinations, such as indirect ophthalmoscopy, ERGs using RETeval, and optic coherent tomography (OCT) measurement, were then performed to confirm diagnosis. Retinal degeneration with cystoid macular edema was observed in both eyes of one 14-year-old female monkey. In her examinations, the full-field ERGs were nonrecordable and the outer layer of the retina in the parafoveal area was not visible on OCT imaging. Moreover, less frequent pigmentary retinal anomalies also were observed in her 3-year-old nephew. His full-field ERGs were almost nonrecordable and the outer layer was not visible in the peripheral retina. His father was her cousin (the son of her mother's older brother) and his mother was her younger half-sibling sister with a different father. The hereditary nature is highly probable (autosomal recessive inheritance suspected). However, whole-exome analysis performed identified no pathogenic mutations in these monkeys.

  17. Reproductive ecology of Emperor Geese: Survival of adult females

    USGS Publications Warehouse

    Petersen, Margaret R.

    1992-01-01

    Life history theory predicts a decrease in survival with increased reproductive effort of individuals. This relationship, however, is highly variable among and within species. I studied the nesting success and survival of adult female Emperor Geese during 1982-1986 and found no direct evidence that differential reproductive effort as measured by the number of eggs laid or hatching success had a significant negative effect on survival to the next breeding season. Incubated clutch size, hatched clutch size, number of parasitic eggs, nest initiation date, hatch date, and mass at hatch were not related to subsequent survival. Of the factors I examined, only an attempt to nest the previous season was related to survival of a female. I suggest that the higher probability of survival among non-nesting adult female Emperor Geese was primarily related to hunting pressure on the nesting area between spring and fall migration. The probability of survival was increased for females with larger clutches, suggesting a positive relationship between brood size and survival.

  18. Effect of ovarian aging on androgen biosynthesis in a cynomolgus macaque model

    PubMed Central

    Ethun, K. F.; Wood, C. E.; Parker, C. R.; Kaplan, J. R.; Chen, H.; Appt, S. E.

    2013-01-01

    Objective The role of androgens in chronic disease pathogenesis, cognitive function and libido during menopause is of increasing interest. The aim of this study was to characterize the distribution and expression of androgenic proteins in the macaque ovary and to investigate the relationship between serum androgen concentrations, follicle number, and the persistence of androgenesis in the aging macaque ovary. Methods The subjects were 26 adult female cynomolgus macaques. Ovaries were immunostained for cytochrome P450 17α-hydroxylase/17–20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3βHSD), and cytochrome b5 (cytb5). Based on primordial follicle counts, animals were divided into tertiles (low (≤200), intermediate (226–1232), and high (2372–4356)) to evaluate differences in androgen staining and changes in serum androgen concentrations following ovariectomy. Results Positive immunostaining for P450c17 and cytb5 within the theca interna layer of growing follicles persisted in advanced atretic follicles and secondary interstitial cells (residual stromal cells). Ovaries with low follicle numbers had less staining for all androgenic proteins compared to ovaries with higher numbers of growing follicles. Immunostaining for cytb5 was the most reliable marker for persistent androgenesis in ovaries with minimal primordial follicle numbers (<100) and residual stromal cells. Following ovariectomy, a significant decrease in testosterone (−27.7%, −30.8%, −27.5%; p < 0.01) and androstenedione (−33.4%, −35.7%, −46.0%; p < 0.01) was observed in monkeys with low, intermediate, and high primordial follicle counts, respectively. Conclusions Despite low follicle numbers, the aging macaque ovary retains the necessary proteins for androgenesis within residual stromal cells and contributes to peripheral androgen concentrations. PMID:21864136

  19. Human IgG subclass cross-species reactivity to mouse and cynomolgus monkey Fcγ receptors.

    PubMed

    Derebe, Mehabaw G; Nanjunda, Rupesh K; Gilliland, Gary L; Lacy, Eilyn R; Chiu, Mark L

    2018-05-01

    In therapeutic antibody discovery and early development, mice and cynomolgus monkey are used as animal models to assess toxicity, efficacy and other properties of candidate molecules. As more candidate antibodies are based on human immunoglobulin (IgG) subclasses, many strategies are pursued to simulate the human system in the test animal. However, translation rate from a successful preclinical trial to an approved drug is extremely low. This may partly be due to differences in interaction of human IgG based candidate molecules to endogenous Fcγ receptors of model animals in comparison to those of human Fcγ receptors. In this study, we compare binding characteristics of human IgG subclasses commonly used in drug development (IgG1, IgG2, IgG4) and their respective Fc silent versions (IgG1σ, IgG2σ, IgG4 PAA) to human, mouse, and cynomolgus monkey Fcγ receptors. To control interactions between Fab and Fc domains, the test IgGs all have the same variable region sequences. We found distinct variations of interaction of human IgG subclasses to model animal Fcγ receptors in comparison to their human counterparts. Particularly, cynomolgus monkey Fcγ receptors showed consistently tighter binding to human IgGs than human Fcγ receptors. Moreover, the presumably Fc silent human IgG4 PAA framework bound to cynomolgus monkey FcγRI with nanomolar affinity while only very weak binding was observed for the human FcγRI. Our results highlighted the need for a thorough in vitro affinity characterization of candidate IgGs against model animal Fcγ receptors and careful design of preclinical studies. Copyright © 2018. Published by Elsevier B.V.

  20. Ontogenetic pattern of gyrification in fetuses of cynomolgus monkeys.

    PubMed

    Sawada, K; Sun, X-Z; Fukunishi, K; Kashima, M; Saito, S; Sakata-Haga, H; Sukamoto, T; Aoki, I; Fukui, Y

    2010-05-19

    The ontogenetic pattern of gyrification and its relationship with cerebral cortical volume were examined in cynomolgus monkey fetuses. T(1)-weighted coronal magnetic resonance (MR) images at 7 T were acquired from the fixed cerebra of three male fetuses, each at embryonic days (EDs) 70 to 150, and the gyrification index (GI) of each slice was estimated. The mean GI was low (1.1-1.2) during EDs 70 to 90, and then increased dramatically on ED 100. The developmental profiles of the rostrocaudal GI distribution revealed that cortical convolution was more frequent in the parietooccipital region than in other regions during EDs 100 to 150, forming an adult-like pattern by ED 150. The mean GI was closely correlated with the volume of cortical gray matter (r=0.9877), and also with the volume of white matter/intermediate zone (r=0.8961). These findings suggest that cortical convolution is correlated with either the maturation of cortical gray matter or the development of white matter bundles. The characteristic GI distribution pattern of catarrhines was formed by ED 150 in correlation with the progressive sulcal infolding in the parietooccipital region of the cerebrum. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Sex and the stimulus-movement effect: Differences in acquisition of autoshaped responding in cynomolgus monkeys.

    PubMed

    Rice, Nathaniel C; Makar, Jennifer R; Myers, Todd M

    2017-03-15

    The stimulus-movement effect refers to the phenomenon in which stimulus discrimination or acquisition of a response is facilitated by moving stimuli as opposed to stationary stimuli. The effect has been found in monkeys, rats, and humans, but the experiments conducted did not provide adequate female representation to investigate potential sex differences. The current experiment analyzed acquisition of stimulus touching in a progressive series of classical conditioning procedures in cynomolgus monkeys (Macaca fascicularis) as a function of sex and stimulus movement. Classical conditioning tasks arrange two or more stimuli in relation to each other with different temporal and predictive relations. Autoshaping procedures overlay operant contingencies onto a classical-conditioning stimulus arrangement. In the present case, a neutral stimulus (a small gray square displayed on a touchscreen) functioned as the conditional stimulus and a food pellet functioned as the unconditional stimulus. Although touching is not required to produce food, with repeated stimulus pairings subjects eventually touch the stimulus. Across conditions of increasing stimulus correlation and temporal contiguity, male monkeys acquired the response faster with a moving stimulus. In contrast, females acquired the response faster with a stationary stimulus. These results demonstrate that the stimulus-movement effect may be differentially affected by sex and indicate that additional experiments with females are needed to determine how sex interacts with behavioral phenomena discovered and elaborated almost exclusively using males. Published by Elsevier Inc.

  2. In Vitro Germ Cell Differentiation from Cynomolgus Monkey Embryonic Stem Cells

    PubMed Central

    Yamauchi, Kaori; Hasegawa, Kouichi; Chuma, Shinichiro; Nakatsuji, Norio; Suemori, Hirofumi

    2009-01-01

    Background Mouse embryonic stem (ES) cells can differentiate into female and male germ cells in vitro. Primate ES cells can also differentiate into immature germ cells in vitro. However, little is known about the differentiation markers and culture conditions for in vitro germ cell differentiation from ES cells in primates. Monkey ES cells are thus considered to be a useful model to study primate gametogenesis in vitro. Therefore, in order to obtain further information on germ cell differentiation from primate ES cells, this study examined the ability of cynomolgus monkey ES cells to differentiate into germ cells in vitro. Methods and Findings To explore the differentiation markers for detecting germ cells differentiated from ES cells, the expression of various germ cell marker genes was examined in tissues and ES cells of the cynomolgus monkey (Macaca fascicularis). VASA is a valuable gene for the detection of germ cells differentiated from ES cells. An increase of VASA expression was observed when differentiation was induced in ES cells via embryoid body (EB) formation. In addition, the expression of other germ cell markers, such as NANOS and PIWIL1 genes, was also up-regulated as the EB differentiation progressed. Immunocytochemistry identified the cells expressing stage-specific embryonic antigen (SSEA) 1, OCT-4, and VASA proteins in the EBs. These cells were detected in the peripheral region of the EBs as specific cell populations, such as SSEA1-positive, OCT-4-positive cells, OCT-4-positive, VASA-positive cells, and OCT-4-negative, VASA-positive cells. Thereafter, the effect of mouse gonadal cell-conditioned medium and growth factors on germ cell differentiation from monkey ES cells was examined, and this revealed that the addition of BMP4 to differentiating ES cells increased the expression of SCP1, a meiotic marker gene. Conclusion VASA is a valuable gene for the detection of germ cells differentiated from ES cells in monkeys, and the identification and

  3. Survival of adult female elk in yellowstone following wolf restoration

    USGS Publications Warehouse

    Evans, S.B.; Mech, L.D.; White, P.J.; Sargeant, G.A.

    2006-01-01

    Counts of northern Yellowstone elk (Cervus elaphus) in northwestern Wyoming and adjacent Montana, USA, have decreased at an average rate of 6-8% per year since wolves (Canis lupus) were reintroduced in 1995. Population growth rates of elk are typically sensitive to variations in adult female survival; populations that are stable or increasing exhibit high adult female survival. We used survival records for 85 radiocollared adult female elk 1-19 years old to estimate annual survival from March 2000 to February 2004. Weighted average annual survival rates were approximately 0.83 (95% CI = 0.77-0.89) for females 1-15 years old and 0.80 (95% CI = 0.73-0.86) for all females. Our estimates were much lower than the rate of 0.99 observed during 1969-1975 when fewer elk were harvested by hunters, wolves were not present, and other predators were less numerous. Of 33 documented deaths included in our analysis, we attributed 11 to hunter harvest, 14 to predation (10 wolf, 2 unknown, 1 cougar [Puma concolor], and 1 bear [Ursus sp.]), 6 to unknown causes, and 2 to winter-kill. Most deaths occurred from December through March. Estimates of cause-specific annual mortality rates were 0.09 (0.05-0.14) for all predators, 0.08 (0.04-0.13) for hunting, and 0.07 (0.03-0.11) for wolves specifically. Wolf-killed elk were typically older (median = 12 yr) than hunter-killed elk (median = 9 yr, P = 0.03). However, elk that winter outside the park where they were exposed to hunting were also younger (median = 7 yr) than elk that we did not observe outside the park (median = 9 yr, P < 0.01). Consequently, differences in ages of elk killed by wolves and hunters may reflect characteristics of elk exposed to various causes of mortality, as well as differences in susceptibility. Unless survival rates of adult females increase, elk numbers are likely to continue declining. Hunter harvest is the only cause of mortality that is amenable to management at the present time.

  4. Adult females and pubic bone growth.

    PubMed

    Fuller, K

    1998-07-01

    Previous research (Tague [1994] Am. J. Phys. Anthropol. 95:27-40) has shown an age effect in pubic bone length among adult women. Tague found that in three prehistoric Native American skeletal samples, women aged 18-24 had a significantly shorter linea terminalis than did women aged 25 and older. The purpose of this research is to determine whether such a difference can be discerned in other female skeletal samples. Three female skeletal samples were used in this analysis: 75 African-American and 42 European-American females aged 18-39 from the Hamann-Todd Collection (collected between 1893 and 1938; Iscan, 1990) and 99 African-American females aged 18-39 from the Terry Collection (collected between 1914 and 1965; Cobb, 1933; Iscan, 1990). Several chord measurements of pubic bone length along the linea terminalis were analyzed by one-tailed t-tests of the separate samples subdivided into two age groups: 18-24 and 25-39 years. Of 15 comparisons between age groups, none differed significantly by age group within each sample. It is concluded that the observed significant difference in pubic bone length in the Native American female skeletal samples cannot be replicated in other samples and that there is no age effect on pubic bone length in the samples tested in this analysis. Tague's findings reflect either the occurrence of late menarche in prehistoric populations or differential survivorship.

  5. Modification of the Fc Region of a Human Anti-oncostatin M Monoclonal Antibody for Higher Affinity to FcRn Receptor and Extension of Half-life in Cynomolgus Monkeys.

    PubMed

    Nnane, Ivo P; Han, Chao; Jiao, Qun; Tam, Susan H; Davis, Hugh M; Xu, Zhenhua

    2017-07-01

    The purpose of this study was to evaluate the pharmacokinetics (PK) of anti-oncostatin M (OSM) IgG1 monoclonal antibodies, CNTO 1119 and its Fc variant (CNTO 8212), which incorporates the LS(Xtend) mutation to extend terminal half-life (T 1/2 ), after a single intravenous (IV) or subcutaneous (SC) administration in cynomolgus monkeys, and to predict human PK. In study 1, single doses of CNTO 1119 and CNTO 8212 were administered IV or SC at 3 mg/kg to cynomolgus monkeys (n = 3 per group). In study 2, single doses of CNTO 8212 were administered IV at 1, 5 or 20 mg/kg, or SC at 5 mg/kg to cynomolgus monkeys (n = 5 per group). Serial blood samples were collected for assessment of serum concentrations of CNTO 1119 and/or CNTO 8212. A two-compartment population PK model with first-order elimination was utilized to simultaneously describe the serum concentrations of CNTO 1119 and CNTO 8212 over time after IV and SC administration in cynomolgus monkeys. The typical population PK parameter estimates for CNTO 1119 in cynomolgus monkeys were clearance (CL) = 2.81 mL/day/kg, volume of distribution of central compartment (V 1 ) = 31.3 mL/kg, volume of distribution of peripheral compartment (V 2 ) = 23.3 mL/kg, absolute bioavailability (F) = 0.84 and T 1/2 = 13.4 days. In comparison, the typical population PK parameter estimates for CNTO 8212 in cynomolgus monkeys were CL = 1.41 mL/day/kg, V 1 = 39.8 mL/kg, V 2 = 32.6 mL/kg, F = 0.75 and T 1/2 = 35.7 days. The mean CL of CNTO 8212 was ~50% lower compared with that for CNTO 1119 in cynomolgus monkeys. The overall volume of distribution (V 1 +V 2 ) for CNTO 8212 was about 32% larger compared with that for CNTO 1119, but generally similar to the vascular volume in cynomolgus monkeys. The T 1/2 of CNTO 8212 was significantly (p < 0.05) longer by about 2.7-fold than that for CNTO 1119 in cynomolgus monkeys. Thus, the modification of the Fc portion of an anti-OSM IgG1 mAb for higher FcRn binding affinity resulted in lower systemic

  6. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gautier, Jean-Charles, E-mail: jean-charles.gautie

    Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- andmore » multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.« less

  7. Enterically transmitted non-A, non-B hepatitis: serial passage of disease in cynomolgus macaques and tamarins and recovery of disease-associated 27- to 34-nm viruslike particles.

    PubMed Central

    Bradley, D W; Krawczynski, K; Cook, E H; McCaustland, K A; Humphrey, C D; Spelbring, J E; Myint, H; Maynard, J E

    1987-01-01

    An experimental model of enterically transmitted non-A, non-B hepatitis (ET-NANBH) was established in tamarins (Saguinus mystax mystax) and cynomolgus macaques (Macaca fascicularis). First-passage animals were inoculated with two different stool suspensions obtained from human patients with well-defined ET-NANBH that originated from Burma and Pakistan, where epidemics of ET-NANBH occur. Both inocula contained 27- ato 34-nm-diameter viruslike particles (VLPs) that were specifically aggregated by acute-phase ET-NANBH sera. ET-NANBH was subpassaged in both tamarins and cynomolgus macaques by using pools of stool suspensions from first-passage animals. One additional passage of disease in cynomolgus macaques resulted in a significantly shortened incubation period and increased severity of disease. VLPs similar to those found in the human inocula were observed in stool specimens of first-, second-, and third-passage cynomolgus macaques and in first- and second-passage tamarins. Our findings indicate that cynomolgus macaques are particularly suitable experimental models for studies of human ET-NANBH. The 27- to 34-nm VLPs found in infected human and primate stools appear to be etiologically linked to disease. Images PMID:3114746

  8. Evaluation of bendectin embryotoxicity in nonhuman primates: II. Double-blind study in term cynomolgus monkeys.

    PubMed

    Hendrickx, A G; Cukierski, M; Prahalada, S; Janos, G; Booher, S; Nyland, T

    1985-10-01

    The embryotoxic and teratogenic potential of Bendectin was assessed in this double-blind study in the cynomolgus monkey (Macaca fascicularis). Bendectin was administered orally at doses approximately two, five, and 20 times the human dose equivalent from 22 +/- 2 through 50 days of gestation. Fetuses were delivered by cesarean section near term and examined for malformations. There was no maternal toxicity as evidenced by maternal weights and physical signs. There was no correlation between dosage and the number of prenatal deaths. No significant abnormalities related to treatment were observed in postdelivery physical examinations, placental evaluations, external and internal gross examinations, or from radiographs of the neonates. Under the conditions of this study the treatment of pregnant cynomolgus monkeys with Bendectin produced no evidence of teratogenicity or embryo-, or fetal-, or maternal toxicity.

  9. Functional neurotoxicity evaluation of noribogaine using video-EEG in cynomolgus monkeys.

    PubMed

    Authier, Simon; Accardi, Michael V; Paquette, Dominique; Pouliot, Mylène; Arezzo, Joseph; Stubbs, R John; Gerson, Ronald J; Friedhoff, Lawrence T; Weis, Holger

    2016-01-01

    Continuous video-electroencephalographic (EEG) monitoring remains the gold standard for seizure liability assessments in preclinical drug safety assessments. EEG monitored by telemetry was used to assess the behavioral and EEG effects of noribogaine hydrochloride (noribogaine) in cynomolgus monkeys. Noribogaine is an iboga alkaloid being studied for the treatment of opioid dependence. Six cynomolgus monkeys (3 per gender) were instrumented with EEG telemetry transmitters. Noribogaine was administered to each monkey at both doses (i.e., 160 and 320mg/kg, PO) with an interval between dosing of at least 6days, and the resulting behavioral and EEG effects were evaluated. IV pentylenetetrazol (PTZ), served as a positive control for induced seizures. The administration of noribogaine at either of the doses evaluated was not associated with EEG evidence of seizure or with EEG signals known to be premonitory signs of increased seizure risk (e.g., sharp waves, unusual synchrony, shifts to high-frequency patterns). Noribogaine was associated with a mild reduction in activity levels, increased scratching, licking and chewing, and some degree of poor coordination and related clinical signs. A single monkey exhibited brief myoclonic movements that increased in frequency at the high dose, but which did not appear to generalize, cluster or to be linked with EEG abnormalities. Noribogaine was also associated with emesis and partial anorexia. In contrast, PTZ was associated with substantial pre-ictal EEG patterns including large amplitude, repetitive sharp waves leading to generalized seizures and to typical post-ictal EEG frequency attenuation. EEG patterns were within normal limits following administration of noribogaine at doses up to 320mg/kg with concurrent clinical signs that correlated with plasma exposures and resolved by the end of the monitoring period. PTZ was invariably associated with EEG paroxysmal activity leading to ictal EEG. In the current study, a noribogaine

  10. AFAST - Adult Female Acne Scoring Tool: an easy-to-use tool for scoring acne in adult females.

    PubMed

    Auffret, N; Claudel, J-P; Leccia, M-T; Poli, F; Farhi, D; Dréno, B

    2016-05-01

    Acne is a concern in adults, especially in women. The specifications in current acne grading systems are not applicable to this particular population. To develop and validate a measurement tool (AFAST: adult female acne scoring tool) for acne in women by taking into account the specific locations of adult female acne, and to evaluate the impact of the photographic modalities on rating reproducibility. Six experts in dermatology rated pictures of 54 women with a phototype from I to IV during two sessions, with an interval of 24 h. They rated the acne severity on the face using the GEA scale (Score 1) together with a new scale to assess acne on the mandibular zone (Score 2). Pictures of 30 women were taken using a standardized photographic device; pictures of the other 24 women were taken by their own dermatologists during daily practice. At session 1, the inter-rater's reproducibility was good for Score 1 with an ICC of 0.77 [0.72-0.83], and excellent for Score 2 with an ICC of 0.87 [0.82-0.91]. Between sessions 1 and 2, the mean intra-rater's reproducibility was excellent for both scores with an ICC of 0.88 [0.84-0.92] for Score 1, and an ICC of 0.87 [0.78-0.92] for Score 2. Photographic modalities had no significant effect on the inter- and intra-rater's reproducibility. For the first time, it has been demonstrated that AFAST can accurately rate acne severity in women. It is a promising, easy-to-use tool for both daily practice and clinical investigation. © 2015 European Academy of Dermatology and Venereology.

  11. The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

    PubMed Central

    Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

    2018-01-01

    Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

  12. Depressive-like behavioral profiles in captive-bred single- and socially-housed rhesus and cynomolgus macaques: a species comparison

    PubMed Central

    Camus, Sandrine M. J.; Rochais, Céline; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

    2014-01-01

    Background: To unravel the causes of major depressive disorder (MDD), the third leading cause of disease burden around the world, ethological animal models have recently been proposed. Our previous studies highlighted a depressive-like profile among single- and socially-housed farm-bred cynomolgus macaques. Although phylogenetically close, cynomolgus and rhesus macaques, the two most commonly used macaque species in biomedical research, differ on several levels such as patterns of aggression, reconciliation, temperament, or dominance styles. The question of whether one captive macaque species was more vulnerable than another in the development of a pathological profile reminiscent of MDD symptoms was explored. Methods: Behavioral data (including body postures, orientations, gaze directions, inter-individual distances, and locations in the cage) were collected in farming conditions. Using an unbiased validated ethological scan-sampling method, followed by multiple correspondence and hierarchical clustering analyses, 40 single- and 35 socially-housed rhesus macaques were assessed. Independently, for each housing condition, inter-species comparisons were made with previously acquired data on farm-bred cynomolgus monkeys. Results: Consistent with our previous studies, we found depressive-like characteristics (e.g., inactivity, low level of investigation and maintenance, long time spent inactive while facing the wall) among single- and socially-housed rhesus macaques. Species-specificities were reported in non-depressive time budgets and in the prevalence of the pathological profiles. Conclusions: Our results suggest that rhesus may be more vulnerable to developing a despair-like state than cynomolgus macaques, both in single- and in social-housing conditions. Therefore, rhesus macaques are more suitable for use as a “spontaneous” model of depressive disorders. PMID:24600363

  13. Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

    PubMed

    Mubiru, James N; Yang, Alice S; Olsen, Christian; Nayak, Sudhir; Livi, Carolina B; Dick, Edward J; Owston, Michael; Garcia-Forey, Magdalena; Shade, Robert E; Rogers, Jeffrey

    2014-01-01

    The function of prostate-specific antigen (PSA) is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR) product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas anubis), and African green monkeys (Chlorocebus aethiops). Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS) of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203).

  14. Genomic Sequencing and Characterization of Cynomolgus Macaque Cytomegalovirus▿

    PubMed Central

    Marsh, Angie K.; Willer, David O.; Ambagala, Aruna P. N.; Dzamba, Misko; Chan, Jacqueline K.; Pilon, Richard; Fournier, Jocelyn; Sandstrom, Paul; Brudno, Michael; MacDonald, Kelly S.

    2011-01-01

    Cytomegalovirus (CMV) infection is the most common opportunistic infection in immunosuppressed individuals, such as transplant recipients or people living with HIV/AIDS, and congenital CMV is the leading viral cause of developmental disabilities in infants. Due to the highly species-specific nature of CMV, animal models that closely recapitulate human CMV (HCMV) are of growing importance for vaccine development. Here we present the genomic sequence of a novel nonhuman primate CMV from cynomolgus macaques (Macaca fascicularis; CyCMV). CyCMV (Ottawa strain) was isolated from the urine of a healthy, captive-bred, 4-year-old cynomolgus macaque of Philippine origin, and the viral genome was sequenced using next-generation Illumina sequencing to an average of 516-fold coverage. The CyCMV genome is 218,041 bp in length, with 49.5% G+C content and 84% protein-coding density. We have identified 262 putative open reading frames (ORFs) with an average coding length of 789 bp. The genomic organization of CyCMV is largely colinear with that of rhesus macaque CMV (RhCMV). Of the 262 CyCMV ORFs, 137 are homologous to HCMV genes, 243 are homologous to RhCMV 68.1, and 200 are homologous to RhCMV 180.92. CyCMV encodes four ORFs that are not present in RhCMV strain 68.1 or 180.92 but have homologies with HCMV (UL30, UL74A, UL126, and UL146). Similar to HCMV, CyCMV does not produce the RhCMV-specific viral homologue of cyclooxygenase-2. This newly characterized CMV may provide a novel model in which to study CMV biology and HCMV vaccine development. PMID:21994460

  15. Tracking cells implanted into cynomolgus monkeys (Macaca fascicularis) using MRI

    PubMed Central

    Ito-Fujishiro, Yasuyo; Koie, Hiroshi; Shibata, Hiroaki; Okabayashi, Sachi; Katakai, Yuko; Ohno, Chieko; Kanayama, Kiichi; Yasutomi, Yasuhiro; Ageyama, Naohide

    2016-01-01

    Regenerative therapy with stem cell transplantation is used to treat various diseases such as coronary syndrome and Buerger’s disease. For instance, stem-cell transplantation into the infarcted myocardium is an innovative and promising strategy for treating heart failure due to ischemic heart disease. Basic studies using small animals have shown that transplanted cells improve blood flow in the infarcted region. Magnetic resonance imaging (MRI) can noninvasively identify and track transplanted cells labeled with superparamagnetic iron oxide (SPIO). Although clinical regenerative therapies have been clinically applied to patients, the fate of implanted cells remains unknown. In addition, follow-up studies have shown that some adverse events can occur after recovery. Therefore, the present study evaluated the ability of MRI using a 3T scanner to track implanted peripheral blood mononuclear cells labeled with SPIO on days 0 and 7 after intramuscular (i.m.) and intravenous (i.v.) injection into a cynomolgus monkey. Labeled cells were visualized at the liver and triceps surae muscle on MR images using T1- and T2-weighted sequences and histologically localized by Prussian blue staining. The transplanted cells were tracked without abnormal clinical manifestations throughout this study. Hence, MRI of cynomolgus monkey transplanted SPIO-labeled cells is a safe and efficient method of tracking labeled cells that could help to determine the mechanisms involved in regenerative therapy. PMID:27062993

  16. Perinatal nicotine exposure increases obesity susceptibility by peripheral leptin resistance in adult female rat offspring.

    PubMed

    Zhang, Wan-Xia; Li, Yin-Ping; Fan, Jie; Chen, Hui-Jian; Li, Gai-Ling; Ouyang, Yan-Qiong; Yan, You-E

    2018-02-01

    Maternal nicotine (NIC) exposure causes overweight, hyperleptinemia and metabolic disorders in adult offspring. Our study aims to explore the underlying mechanism of perinatal NIC exposure increases obesity susceptibility in adult female rat offspring. In our model, we found that adult NIC-exposed females presented higher body weight and subcutaneous and visceral fat mass, as well as larger adipocytes, while no change was found in food intake. Serum profile showed a higher serum glucose, insulin and leptin levels in NIC-exposed females. In adipose tissue and liver, the leptin signaling pathway was blocked at 26 weeks, presented lower Janus tyrosine kinase 2 and signal transducer and activator of transcription 3 gene expression, higher suppressor of cytokine signaling 3 gene expression (in adipose tissue) and lower leptin receptors gene expression (in liver), indicating that peripheral leptin resistance occurred in NIC-exposed adult females. In female rats, the expression of lipolysis genes was affected dominantly in adipose tissue, but lipogenesis genes was affected in liver. Furthermore, the glucose and insulin tolerance tests showed a delayed glucose clearance and a higher area under the curve in NIC-exposed females. Therefore, perinatal NIC exposure programed female rats for adipocyte hypertrophy and obesity in adult life, through the leptin resistance in peripheral tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Anthropometric and mass distribution characteristics of the adult female.

    DOT National Transportation Integrated Search

    1983-09-01

    This study of 46 living adult females is part of a long-range research program designed to establish valid analytical relationships between readily measured body dimensions and mass distribution characteristics of living populations. Presented in thi...

  18. Adolescent females with a substance use disorder: affiliations with adult male sexual partners.

    PubMed

    Castillo Mezzich, A; Giancola, P R; Lu, S Y; Parks, S M; Ratica, G M; Dunn, M

    1999-01-01

    To test the hypothesis that low socioeconomic status (SES), a disturbed parent-daughter relationship, early sexual development, and antisocial behavior are risk factors in adolescent females affiliating with adult male sexual partners. To determine whether the relation between these risk factors and affiliating with adult male sexual partners is stronger in females with greater, rather than fewer, substance use disorders (SUD). Subjects were 180 adolescent females with SUD and 87 normal controls (14-18 years of age). The SUD group had a lower SES and more negative parent-daughter interactions, and exhibited greater antisocial tendencies. Also, the SUD group showed a more frequent affiliation with adult male sexual partners. Chronological age, age of menarche (sexual development), antisocial behavior, and quality of the parent-daughter relationship were significantly associated with affiliation with adult male sexual partners. Moreover, the number of SUD diagnoses enhanced the relation between the quality of the parent-daughter relationship and antisocial behavior with affiliation with adult male sexual partners. From a prevention perspective, interventions directed at enhancing child rearing practices, communication skills, and involvement in children's needs and activities might result in improved parent-child attachments that may attentuate young women's propensities to become involved in antisocial behavior and affiliate with adult sexual partners. Also, the risk imposed by an early sexual maturation may be offset by enhancing the female adolescent's social skills to select non-deviant and supportive male partners.

  19. Myotoxicity of gemfibrozil in Cynomolgus monkey model and its relationship to pharmacokinetic properties

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu Aiming; Xie Shuilin; Sun He

    2009-03-15

    Fibrate drugs are PPAR{alpha} agonists prescribed for the treatment of dyslipidemia. Severe myotoxicity has been reportedly associated with their use albeit at a low frequency, especially for gemfibrozil. Few studies have investigated the mechanism of fibrate-induced myotoxicity in vivo. Considering the apparent species-related differences in PPAR{alpha} agonist-induced hepatotoxicity, we studied the myotoxicity of gemfibrozil in a Cynomolgus monkey model and explored the relationship between myotoxicity and pharmacokinetics. Six Cynomolgus monkeys were dosed with gemfibrozil twice daily at 600 mg/kg/day for the first two periods (P1 and P2, 8 days and 9 days respectively) and 300 mg/kg/day for the third periodmore » (P3, 14 days). Creatine kinase and myoglobin were measured, together with hepatotoxicity and nephrotoxicity markers. Behavioral responses were recorded for indication of toxicity. Pharmacokinetics was carried out following the 16th dosage of P1 and 17th dosage of P2 when myotoxicity was identified. Multivariable data analysis was employed to explore the relationship between pharmacokinetic parameters and myotoxicity markers. Consequently, myotoxicity occurred in monkey no. 2 (M2) and M6 in P1, M3 and M4 in P2, M3 and M6 in P3. Data analysis showed T80-150 (sustained time above the given concentration) contributed for myotoxicity discriminance and correlated with myotoxicity risk. This study revealed Cynomolgus monkey may be a good animal model for myotoxicity evaluation with sensitivity, reproducibility and similarities to humans. More interestingly, they exhibited a much higher incidence of myotoxicity than that of humans. Sustained high drug concentration plays an important role for the occurrence of myotoxicity. This may suggest an influence of drug transport and metabolism on myotoxicity.« less

  20. Myotoxicity of Gemfibrozil in Cynomolgus Monkey Model and Its Relationship to Pharmacokinetic Properties

    PubMed Central

    Liu, Aiming; Xie, Shuilin; Sun, He; Gonzalez, Frank J.; Wei, Xiaoxiong; Dai, Renke

    2008-01-01

    Fibrate drugs are PPARα agonists prescribed for the treatment of dyslipidemia. Severe myotoxicity has been reported associated with their use albeit at a low frequency, especially for gemfibrozil. Few studies have investigated the mechanism of fibrate-induced myotoxicity in vivo. Considering the apparent species-related differences in PPARα agonist-induced hepatotoxicity, we studied the myotoxicity of gemfibrozil in a Cynomolgus monkey model and explored the relationship between myotoxicity and pharmacokinetics. Six Cynomolgus monkeys were dosed with gemfibrozil twice daily at 600 mg/kg/day for the first two periods (P1 and P2, 8 days and 9 days respectively) and 300 mg/kg/day for the third period (P3, 14 days). Creatine kinase and myoglobin were measured, together with hepatotoxicity and nephrotoxicity markers. Behavioral responses were recorded for indication of toxicity. Pharmacokinetics was carried out following the 16th dosage of P1 and 17th dosage of P2 when myotoxicity was identified. Multivariable data analysis was employed to explore the relationship between pharmacokinetic parameters and myotoxicity markers. Consequently, myotoxicity occurred in monkey #2 (M2) and M6 in P1, M3 and M4 in P2, M3 and M6 in P3. Data analysis showed T80-150 (sustained time above the given concentration) contributed for myotoxicity discriminance and correlated with myotoxicity risk. This study revealed Cynomolgus monkey may be a good animal model for myotoxicity evaluation with sensitivity, reproducibility and similarities to humans. More interestingly they exhibited a much higher incidence of myotoxicity than that of human. Sustained high drug concentration plays an important role for the occurrence of myotoxicity. This may suggest an influence of drug transport and metabolism on myotoxicity. PMID:19150455

  1. Motivational and mindfulness intervention for young adult female marijuana users

    PubMed Central

    de Dios, Marcel A.; Herman, Debra S.; Britton, Willoughby B.; Hagerty, Claire E.; Anderson, Bradley J.; Stein, Michael D.

    2011-01-01

    This pilot study tested the efficacy of a brief intervention using motivational interviewing (MI) plus mindfulness meditation (MM) to reduce marijuana use among young adult female. Thirty-four female marijuana users between the ages of 18–29 were randomized to either the intervention group (n = 22), consisting of 2 sessions of MI-MM or an assessment-only control group (n = 12). Participants’ marijuana use was assessed at baseline, 1, 2, and 3 months post-treatment. Fixed-effects regression modeling was used to analyze treatment effects. Participants randomized to the intervention group were found to use marijuana on 6.15 (z = −2.42, p=.015), 7.81 (z = −2.78, p=.005), and 6.83 (z = −2.23, p=.026) fewer days at months 1, 2, and 3, respectively, than controls. Findings from this pilot study provide preliminary evidence for the feasibility and effectiveness of a brief MI-MM for young adult female marijuana users. PMID:21940136

  2. Seasonal survival of adult female mottled ducks

    USGS Publications Warehouse

    Moon, Jena A.; Haukos, David A.; Conway, Warren C.

    2017-01-01

    The mottled duck (Anas fulgivula) is a non-migratory duck dependent on coastal habitats to meet all of its life cycle requirements in the Western Gulf Coast (WGC) of Texas and Louisiana, USA. This population of mottled ducks has experienced a moderate decline during the past 2 decades. Adult survival has been identified as an important factor influencing population demography. Previous work based on band-recovery data has provided only annual estimates of survival. We assessed seasonal patterns of female mottled duck survival from 2009 to 2012 using individuals marked with satellite platform transmitter terminals (PTTs). We used temperature and movement sensors within each PTT to indicate potential mortality events. We estimated cumulative weekly survival and ranked factors influential in patterns of mortality using known-fate modeling in Program MARK. Models included 4 predictors: week; hunting and non-hunting periods; biological periods defined as breeding, brooding, molt, and pairing; and mass at time of capture. Models containing hunt periods, during and outside the mottled duck season, comprised essentially 100% of model weights where both legal and illegal harvest had a negative influence on mottled duck survival. Survival rates were low during 2009–2011 (12–38% annual rate of survival), when compared with the long-term banding average of 53% annual survival. During 2011, survival of female mottled ducks was the lowest annual rate (12%) ever documented and coincided with extreme drought. Management actions maximizing the availability of wetlands and associated upland habitats during hunting seasons and drought conditions may increase adult female mottled duck survival.

  3. Selection of appropriate reference genes for RT-qPCR analysis in a streptozotocin-induced Alzheimer's disease model of cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Park, Sang-Je; Kim, Young-Hyun; Lee, Youngjeon; Kim, Kyoung-Min; Kim, Heui-Soo; Lee, Sang-Rae; Kim, Sun-Uk; Kim, Sang-Hyun; Kim, Ji-Su; Jeong, Kang-Jin; Lee, Kyoung-Min; Huh, Jae-Won; Chang, Kyu-Tae

    2013-01-01

    Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) has been widely used to quantify relative gene expression because of the specificity, sensitivity, and accuracy of this technique. In order to obtain reliable gene expression data from RT-qPCR experiments, it is important to utilize optimal reference genes for the normalization of target gene expression under varied experimental conditions. Previously, we developed and validated a novel icv-STZ cynomolgus monkey model for Alzheimer's disease (AD) research. However, in order to enhance the reliability of this disease model, appropriate reference genes must be selected to allow meaningful analysis of the gene expression levels in the icv-STZ cynomolgus monkey brain. In this study, we assessed the expression stability of 9 candidate reference genes in 2 matched-pair brain samples (5 regions) of control cynomolgus monkeys and those who had received intracerebroventricular injection of streptozotocin (icv-STZ). Three well-known analytical programs geNorm, NormFinder, and BestKeeper were used to choose the suitable reference genes from the total sample group, control group, and icv-STZ group. Combination analysis of the 3 different programs clearly indicated that the ideal reference genes are RPS19 and YWHAZ in the total sample group, GAPDH and RPS19 in the control group, and ACTB and GAPDH in the icv-STZ group. Additionally, we validated the normalization accuracy of the most appropriate reference genes (RPS19 and YWHAZ) by comparison with the least stable gene (TBP) using quantification of the APP and MAPT genes in the total sample group. To the best of our knowledge, this research is the first study to identify and validate the appropriate reference genes in cynomolgus monkey brains. These findings provide useful information for future studies involving the expression of target genes in the cynomolgus monkey.

  4. New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

    PubMed

    Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

    2015-08-01

    A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

  5. Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008.

    PubMed

    Sakai, Kouji; Nagata, Noriyo; Ami, Yasushi; Seki, Fumio; Suzaki, Yuriko; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Fukushi, Shuetsu; Mizutani, Tetsuya; Yoshikawa, Tomoki; Otsuki, Noriyuki; Kurane, Ichiro; Komase, Katsuhiro; Yamaguchi, Ryoji; Hasegawa, Hideki; Saijo, Masayuki; Takeda, Makoto; Morikawa, Shigeru

    2013-01-01

    Canine distemper virus (CDV) has recently expanded its host range to nonhuman primates. A large CDV outbreak occurred in rhesus monkeys at a breeding farm in Guangxi Province, China, in 2006, followed by another outbreak in rhesus monkeys at an animal center in Beijing in 2008. In 2008 in Japan, a CDV outbreak also occurred in cynomolgus monkeys imported from China. In that outbreak, 46 monkeys died from severe pneumonia during a quarantine period. A CDV strain (CYN07-dV) was isolated in Vero cells expressing dog signaling lymphocyte activation molecule (SLAM). Phylogenic analysis showed that CYN07-dV was closely related to the recent CDV outbreaks in China, suggesting continuing chains of CDV infection in monkeys. In vitro, CYN07-dV uses macaca SLAM and macaca nectin4 as receptors as efficiently as dog SLAM and dog nectin4, respectively. CYN07-dV showed high virulence in experimentally infected cynomolgus monkeys and excreted progeny viruses in oral fluid and feces. These data revealed that some of the CDV strains, like CYN07-dV, have the potential to cause acute systemic infection in monkeys.

  6. Reduced Marker of Vascularization in the Anterior Hippocampus in a Female Monkey Model of Depression

    PubMed Central

    Kalidindi, Anisha; Kelly, Sean D.; Singleton, Kaela S.; Guzman, Dora; Merrill, Liana; Willard, Stephanie L.; Shively, Carol A.; Neigh, Gretchen N.

    2016-01-01

    Depression is a common and debilitating mood disorder that impacts women more often than men. The mechanisms that result in depressive behaviors are not fully understood; however, the hippocampus has been noted as a key structure in the pathophysiology of depression. In addition to neural implications of depression, the cardiovascular system is impacted. Although not as commonly considered, the cerebrovasculature is critical to brain function, impacted by environmental stimuli, and is capable of altering neural function and thereby behavior. In the current study, we assessed the relationship between depressive behavior and a marker of vascularization of the hippocampus in adult female cynomolgus macaques (Macaca fascicularis). Similar to previously noted impacts on neuropil and glia, the depressed phenotype predicts a reduction in a marker of vascular length in the anterior hippocampus. These data reinforce the growing recognition of the effects of depression on vasculature and support further consideration of vascular endpoints in studies aimed at the elucidation of the mechanisms underlying depression. PMID:27423324

  7. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

    PubMed

    Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

    2016-03-24

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

  8. Comprehensive Evaluation for Substrate Selectivity of Cynomolgus Monkey Cytochrome P450 2C9, a New Efavirenz Oxidase.

    PubMed

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-07-01

    Cynomolgus monkeys are widely used as primate models in preclinical studies, because of their evolutionary closeness to humans. In humans, the cytochrome P450 (P450) 2C enzymes are important drug-metabolizing enzymes and highly expressed in livers. The CYP2C enzymes, including CYP2C9, are also expressed abundantly in cynomolgus monkey liver and metabolize some endogenous and exogenous substances like testosterone, S-mephenytoin, and diclofenac. However, comprehensive evaluation regarding substrate specificity of monkey CYP2C9 has not been conducted. In the present study, 89 commercially available drugs were examined to find potential monkey CYP2C9 substrates. Among the compounds screened, 20 drugs were metabolized by monkey CYP2C9 at a relatively high rates. Seventeen of these compounds were substrates or inhibitors of human CYP2C9 or CYP2C19, whereas three drugs were not, indicating that substrate specificity of monkey CYP2C9 resembled those of human CYP2C9 or CYP2C19, with some differences in substrate specificities. Although efavirenz is known as a marker substrate for human CYP2B6, efavirenz was not oxidized by CYP2B6 but by CYP2C9 in monkeys. Liquid chromatography-mass spectrometry analysis revealed that monkey CYP2C9 and human CYP2B6 formed the same mono- and di-oxidized metabolites of efavirenz at 8 and 14 positions. These results suggest that the efavirenz 8-oxidation could be one of the selective markers for cynomolgus monkey CYP2C9 among the major three CYP2C enzymes tested. Therefore, monkey CYP2C9 has the possibility of contributing to limited specific differences in drug oxidative metabolism between cynomolgus monkeys and humans. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Depressive Symptoms in Older Female Carers of Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Chou, Y. C.; Pu, C-Y.; Fu, L-Y.; Kroger, T.

    2010-01-01

    Background: This survey study aims to examine the prevalence and factors associated with depressive symptoms among primary older female family carers of adults with intellectual disabilities (ID). Method: In total, 350 female family carers aged 55 and older took part and completed the interview in their homes. The survey package contained…

  10. R-warfarin clearances from plasma associated with polymorphic cytochrome P450 2C19 and simulated by individual physiologically based pharmacokinetic models for 11 cynomolgus monkeys.

    PubMed

    Utoh, Masahiro; Kusama, Takashi; Miura, Tomonori; Mitsui, Marina; Kawano, Mirai; Hirano, Takahiro; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

    2018-02-01

    1. Cynomolgus monkey cytochrome P450 2C19 (formerly known as P450 2C75), homologous to human P450 2C19, has been identified as R-warfarin 7-hydroxylase. In this study, simulations of R-warfarin clearance in individual cynomolgus monkeys genotyped for P450 2C19 p.[(Phe100Asn; Ala103Val; Ile112Leu)] were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling. 2. Pharmacokinetic parameters and absorption rate constants, volumes of the systemic circulation, and hepatic intrinsic clearances for individual PBPK models were estimated for eleven cynomolgus monkeys. 3. One-way ANOVA revealed significant effects of the genotype (p < 0.01) on the observed elimination half-lives and areas under the curves of R-warfarin among the homozygous mutant, heterozygous mutant, and wild-type groups. R-Warfarin clearances in individual cynomolgus monkeys genotyped for P450 2C19 were simulated by simplified PBPK modeling. The modeled hepatic intrinsic clearances were significantly associated with the P450 2C19 genotypes. The liver microsomal elimination rates of R-warfarin for individual animals after in vivo administration showed significant reductions associated with the genotype (p < 0.01). 4. This study provides important information to help simulate clearances of R-warfarin and related medicines associated with polymorphic P450 2C19 in individual cynomolgus monkeys, thereby facilitating calculation of the fraction of hepatic clearance.

  11. Second-Language Acquisition, Culture Shock, and Language Stress of Adult Female Latina Students in New York

    ERIC Educational Resources Information Center

    Buttaro, Lucia

    2004-01-01

    The purpose of this study was to identify and describe the educational, cultural, and linguistic adjustments and experiences encountered by Hispanic adult females in learning English as a second language (ESL) and the relation of these experiences to the variables of language, culture, and education of adult Hispanic females. Adult ESL learners…

  12. Triflumuron Effects on the Physiology and Reproduction of Rhodnius prolixus Adult Females

    PubMed Central

    Henriques, Bianca Santos; Mello, Cícero Brasileiro; Silva, Lucas Rangel; Codogno, Thaís Franco; Oliveira, Alyne F. R.; Marinho, Lourena Pinheiro; Lima, José Bento Pereira; Feder, Denise; Gonzalez, Marcelo Salabert; Azambuja, Patricia

    2016-01-01

    We evaluated the efficacy of the growth regulator triflumuron (TFM) in inducing mortality and disrupting both oviposition and egg hatching in Rhodnius prolixus adult females. TFM was administered via feeding, topically or by continuous contact with impregnated surfaces. Feeding resulted in mild biological effects compared with topical and impregnated surfaces. One day after treatment, the highest mortality levels were observed with topical surface and 30 days later both topical and impregnated surfaces induced higher mortalities than feeding. Oral treatment inhibited oviposition even at lower doses, and hatching of eggs deposited by treated females was similarly affected by the three delivery modes. Topical treatment of eggs deposited by nontreated females significantly reduced hatching. However, treatment per contact of eggs oviposited by untreated females did not disrupt eclosion. Additionally, oral treatment increased the number of immature oocytes per female, and topical treatment reduced the mean size of oocytes. TFM also affected carcass chitin content, diuresis, and innate immunity of treated insects. These results suggest that TFM acts as a potent growth inhibitor of R. prolixus adult females and has the potential to be used in integrated vector control programs against hematophagous triatomine species. PMID:27822479

  13. Triflumuron Effects on the Physiology and Reproduction of Rhodnius prolixus Adult Females.

    PubMed

    Henriques, Bianca Santos; Genta, Fernando Ariel; Mello, Cícero Brasileiro; Silva, Lucas Rangel; Codogno, Thaís Franco; Oliveira, Alyne F R; Marinho, Lourena Pinheiro; Valle, Denise; Lima, José Bento Pereira; Feder, Denise; Gonzalez, Marcelo Salabert; Azambuja, Patricia

    2016-01-01

    We evaluated the efficacy of the growth regulator triflumuron (TFM) in inducing mortality and disrupting both oviposition and egg hatching in Rhodnius prolixus adult females. TFM was administered via feeding, topically or by continuous contact with impregnated surfaces. Feeding resulted in mild biological effects compared with topical and impregnated surfaces. One day after treatment, the highest mortality levels were observed with topical surface and 30 days later both topical and impregnated surfaces induced higher mortalities than feeding. Oral treatment inhibited oviposition even at lower doses, and hatching of eggs deposited by treated females was similarly affected by the three delivery modes. Topical treatment of eggs deposited by nontreated females significantly reduced hatching. However, treatment per contact of eggs oviposited by untreated females did not disrupt eclosion. Additionally, oral treatment increased the number of immature oocytes per female, and topical treatment reduced the mean size of oocytes. TFM also affected carcass chitin content, diuresis, and innate immunity of treated insects. These results suggest that TFM acts as a potent growth inhibitor of R. prolixus adult females and has the potential to be used in integrated vector control programs against hematophagous triatomine species.

  14. Successful passive and active immunization of cynomolgus monkeys against hepatitis E.

    PubMed Central

    Tsarev, S A; Tsareva, T S; Emerson, S U; Govindarajan, S; Shapiro, M; Gerin, J L; Purcell, R H

    1994-01-01

    Virtually full protection against hepatitis E and partial or complete protection against infection with hepatitis E virus (HEV) were achieved in passively or actively immunized cynomolgus monkeys. Hepatitis, viremia, and shedding of the virus in feces were detected in all nonimmunized animals that were challenged with HEV. HEV titers detected by reverse transcriptase PCR were higher in feces than in serum of nonimmunized animals. Anti-HEV antibody titers at the time of challenge ranged between 1:40 and 1:200 in animals passively immunized with convalescent plasma from a cynomolgus monkey previously infected with HEV and between 1:100 and 1:10,000 in animals actively immunized with a recombinant 55-kDa open reading frame 2 protein. The estimated 50% protective titer of passively acquired anti-HEV antibodies was 1:40. Although only one of four passively immunized animals showed histopathologic evidence of hepatitis, all four were infected after challenge; however, the titers of HEV in serum and feces were lower in the passively immunized animals than in the nonimmunized group. The actively immunized animals developed neither hepatitis nor viremia when challenged with HEV and virus was either not detected or was present in low titer in feces. The protective response was a function of the ELISA anti-HEV antibody titer at the time of challenge and the immunization schedule. PMID:7937861

  15. Dental caries experience and treatment needs of an adult female population in Nigeria.

    PubMed

    Lawal, Folake; Alade, Omolola

    2017-09-01

    Experience and awareness of adult females concerning dental caries is important in its prevention particularly in children because of their natural role as care givers. To determine the prevalence of dental caries and treatment needs in an adult female Nigerian population. In this cross-sectional study, adult females attending outreach programmes were examined for dental caries using the Decayed Missing and Filled Teeth caries index (DMFT). Socio-demographic variables were also recorded and statistical analysis done with SPSS software. A total of 430 females aged 16 to 59 years participated in the outreach programme out of which 109 (25.3%) had a DMFT score > 0. Mean DMFT was 0.7 ± 1.6. Fifty-five (12.8%) participants had decayed teeth, 78 (18.1 %) had missing teeth and 10(2.3%) had filled teeth. The treatment need was 34.3%, restorative index was 13.3% and significant caries index was 2.0. There were significant differences in caries experience based on age, marital status and educational qualifications of participants p < 0.05. The prevalence of dental caries among the study group was low but the treatment need was high. Younger females, singles and those with lower educational qualifications had a higher dental caries experience.

  16. Zika viral dynamics and shedding in rhesus and cynomolgus macaques

    DOE PAGES

    Osuna, Christa E.; Lim, So -Yon; Deleage, Claire; ...

    2016-10-03

    Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection wasmore » cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Finally, early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans.« less

  17. Zika viral dynamics and shedding in rhesus and cynomolgus macaques

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Osuna, Christa E.; Lim, So -Yon; Deleage, Claire

    Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection wasmore » cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Finally, early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans.« less

  18. The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey.

    PubMed

    Schoenfeld, Heidi A; West, Tim; Verghese, Philip B; Holubasch, Mary; Shenoy, Neeta; Kagan, David; Buono, Chiara; Zhou, Wei; DeCristofaro, Marc; Douville, Julie; Goodrich, Geoffrey G; Mansfield, Keith; Saravanan, Chandra; Cumin, Frederic; Webb, Randy L; Bateman, Randall J

    2017-05-15

    Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p=0.026), Aβ1-40 (35.2%; p=0.04) and Aβtotal (29.8%; p=0.04) acutely; this returned to normal as expected with repeated dosing for 15days. CSF concentrations of newly generated Aβ (AUC (0-24h) ) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p=0.039) and day 15 (34.7%; p=0.0003) and in shorter forms Aβ1-40 (23.4%; p=0.009), Aβ1-38 (64.1%; p=0.0001) and Aβtotal (50.45%; p=0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300mg/kg) or vehicle control for 39weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance of these findings. Copyright

  19. Infectivity titration of a prototype strain of hepatitis E virus in cynomolgus monkeys.

    PubMed

    Tsarev, S A; Tsareva, T S; Emerson, S U; Yarbough, P O; Legters, L J; Moskal, T; Purcell, R H

    1994-06-01

    The infectivity titer of a standard stock of the SAR-55 strain of hepatitis E virus (HEV) was determined in cynomolgus macaques (Macaca fascicularis) and the effect of dose on the course of the infection was examined by weekly monitoring of alanine aminotransferase (ALT) and anti-HEV levels. Antibody to HEV (anti-HEV) was measured with ELISAs based on ORF-2 recombinant antigens consisting of either a 55 kDa region expressed in insect cells or shorter regions expressed as fusion proteins in bacteria. The ELISA based on the 55 kDa antigen was generally more sensitive. The infectivity titer of SAR-55 was 10(6) cynomolgus 50% infectious doses per gram of feces. The infectivity titer corresponded to the HEV genome titer of the inoculum as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Anti-HEV IgM was detected in only a portion of the animals that had an anti-HEV IgG response. Biochemical evidence of hepatitis was most prominent in animals that were inoculated with the higher concentrations of virus and the incubation period to seroconversion was prolonged in animals that received the lower doses.

  20. Integrated pharmacokinetic, pharmacodynamic and immunogenicity profiling of an anti-CCL21 monoclonal antibody in cynomolgus monkeys.

    PubMed

    Dudal, S; Subramanian, K; Flandre, T; Law, W S; Lowe, P J; Skerjanec, A; Genin, J-C; Duval, M; Piequet, A; Cordier, A; Jarai, G; Van Heeke, G; Taplin, S; Krantz, C; Jones, S; Warren, A P; Brennan, F R; Sims, J; Lloyd, P

    2015-01-01

    QBP359 is an IgG1 human monoclonal antibody that binds with high affinity to human CCL21, a chemokine hypothesized to play a role in inflammatory disease conditions through activation of resident CCR7-expressing fibroblasts/myofibroblasts. The pharmacokinetics (PK) and pharmacodynamics (PD) of QBP359 in non-human primates were characterized through an integrated approach, combining PK, PD, immunogenicity, immunohistochemistry (IHC) and tissue profiling data from single- and multiple-dose experiments in cynomolgus monkeys. When compared with regular immunoglobulin typical kinetics, faster drug clearance was observed in serum following intravenous administration of 10 mg/kg and 50 mg/kg of QBP359. We have shown by means of PK/PD modeling that clearance of mAb-ligand complex is the most likely explanation for the rapid clearance of QBP359 in cynomolgus monkey. IHC and liquid chromatography mass spectrometry data suggested a high turnover and synthesis rate of CCL21 in tissues. Although lymphoid tissue was expected to accumulate drug due to the high levels of CCL21 present, bioavailability following subcutaneous administration in monkeys was 52%. In human disease states, where CCL21 expression is believed to be expressed at 10-fold higher concentrations compared with cynomolgus monkeys, the PK/PD model of QBP359 and its binding to CCL21 suggested that very large doses requiring frequent administration of mAb would be required to maintain suppression of CCL21 in the clinical setting. This highlights the difficulty in targeting soluble proteins with high synthesis rates.

  1. Simian varicella virus reactivation in cynomolgus monkeys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mahalingam, Ravi; Traina-Dorge, Vicki; Wellish, Mary

    2007-11-10

    SVV infection of primates closely resembles VZV infection of humans. Like VZV, SVV becomes latent in ganglionic neurons. We used this model to study the effect of immunosuppression on varicella reactivation. Cynomolgus monkeys latently infected with SVV were irradiated and treated with tacrolimus and prednisone. Of four latently infected monkeys that were immunosuppressed and subjected to the stress of transportation and isolation, one developed zoster, and three others developed features of subclinical reactivation. Another non-immunosuppressed latently infected monkey that was subjected to the same stress of travel and isolation showed features of subclinical reactivation. Virus reactivation was confirmed not onlymore » by the occurrence of zoster in one monkey, but also by the presence of late SVV RNA in ganglia, and the detection of SVV DNA in non-ganglionic tissue, and SVV antigens in skin, ganglia and lung.« less

  2. Analysis of 10,000 ESTs from lymphocytes of the cynomolgus monkey to improve our understanding of its immune system

    PubMed Central

    Chen, Wei-Hua; Wang, Xue-Xia; Lin, Wei; He, Xiao-Wei; Wu, Zhen-Qiang; Lin, Ying; Hu, Song-Nian; Wang, Xiao-Ning

    2006-01-01

    Background The cynomolgus monkey (Macaca fascicularis) is one of the most widely used surrogate animal models for an increasing number of human diseases and vaccines, especially immune-system-related ones. Towards a better understanding of the gene expression background upon its immunogenetics, we constructed a cDNA library from Epstein-Barr virus (EBV)-transformed B lymphocytes of a cynomolgus monkey and sequenced 10,000 randomly picked clones. Results After processing, 8,312 high-quality expressed sequence tags (ESTs) were generated and assembled into 3,728 unigenes. Annotations of these uniquely expressed transcripts demonstrated that out of the 2,524 open reading frame (ORF) positive unigenes (mitochondrial and ribosomal sequences were not included), 98.8% shared significant similarities (E-value less than 1e-10) with the NCBI nucleotide (nt) database, while only 67.7% (E-value less than 1e-5) did so with the NCBI non-redundant protein (nr) database. Further analysis revealed that 90.0% of the unigenes that shared no similarities to the nr database could be assigned to human chromosomes, in which 75 did not match significantly to any cynomolgus monkey and human ESTs. The mapping regions to known human genes on the human genome were described in detail. The protein family and domain analysis revealed that the first, second and fourth of the most abundantly expressed protein families were all assigned to immunoglobulin and major histocompatibility complex (MHC)-related proteins. The expression profiles of these genes were compared with that of homologous genes in human blood, lymph nodes and a RAMOS cell line, which demonstrated expression changes after transformation with EBV. The degree of sequence similarity of the MHC class I and II genes to the human reference sequences was evaluated. The results indicated that class I molecules showed weak amino acid identities (<90%), while class II showed slightly higher ones. Conclusion These results indicated that the

  3. Pulmonary cestodiasis in a cynomolgus monkey (Macaca fascicularis).

    PubMed

    Guillot, L M; Green, L C

    1992-04-01

    Cestodiasis in primates has been noted historically to occur quite frequently, although tissue damage and clinical signs may or may not be apparent. Larval cestodes, such as hydatid cysts or cysticercus cysts, are known to cause extensive tissue damage, while other larval cestodes, such as tetrathyridia, cause minimal damage to the host. This case history concerns an apparently healthy cynomolgus monkey that was part of a surgical study. During the study, all parameters were normal. The monkey died 3 hours postsurgery. The apparent cause of death was respiratory arrest. At necropsy, it was discovered there were 1- to 3-mm-diameter cysts, which on transection extruded 2- to 5-mm-long larvae. The larvae could not be positively identified; however, they resembled tetrathyridia of Mesocestoides sp.

  4. Zolpidem generalization and antagonism in male and female cynomolgus monkeys trained to discriminate 1.0 or 2.0 g/kg ethanol.

    PubMed

    Helms, Christa M; Rogers, Laura S M; Waters, Courtney A; Grant, Kathleen A

    2008-07-01

    The subtypes of gamma-aminobutyric acid (GABA)(A) receptors mediating the discriminative stimulus effects of ethanol in nonhuman primates are not completely identified. The GABA(A) receptor positive modulator zolpidem has high, intermediate, and low activity at receptors containing alpha(1), alpha(2/3), and alpha(5) subunits, respectively, and partially generalizes from ethanol in several species. The partial inverse agonist Ro15-4513 has the greatest affinity for alpha(4/6)-containing receptors, higher affinity for alpha(5)- and lower, but equal, affinity for alpha(1)- and alpha(2/3)-, containing GABA(A) receptors, and antagonizes the discriminative stimulus effects of ethanol. This study assessed Ro15-4513 antagonism of the generalization of zolpidem from ethanol in male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 g/kg (n = 10) or 2.0 g/kg (n = 7) ethanol (i.g.) from water with a 30-minute pretreatment interval. Zolpidem (0.017 to 5.6 mg/kg, i.m.) completely generalized from ethanol (>or=80% of total session responses on the ethanol-appropriate lever) for 6/7 monkeys trained to discriminate 2.0 g/kg and 4/10 monkeys trained to discriminate 1.0 g/kg ethanol. Zolpidem partially generalized from 1.0 or 2.0 g/kg ethanol in 6/7 remaining monkeys. Ro15-4513 (0.003 to 0.30 mg/kg, i.m., 5-minute pretreatment) shifted the zolpidem dose-response curve to the right in all monkeys showing generalization. Analysis of apparent pK(B) from antagonism tests suggested that the discriminative stimulus effects of ethanol common with zolpidem are mediated by low-affinity Ro15-4513 binding sites. Main effects of sex and training dose indicated greater potency of Ro15-4513 in males and in monkeys trained to discriminate 1.0 g/kg ethanol. Ethanol and zolpidem share similar discriminative stimulus effects most likely through GABA(A) receptors that contain alpha(1) subunits, however, antagonism by Ro15-4513 of zolpidem generalization

  5. Influenza virus A/Anhui/1/2013 (H7N9) replicates efficiently in the upper and lower respiratory tracts of cynomolgus macaques.

    PubMed

    de Wit, Emmie; Rasmussen, Angela L; Feldmann, Friederike; Bushmaker, Trenton; Martellaro, Cynthia; Haddock, Elaine; Okumura, Atsushi; Proll, Sean C; Chang, Jean; Gardner, Don; Katze, Michael G; Munster, Vincent J; Feldmann, Heinz

    2014-08-12

    In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277-2285, 2013, doi:10.1056/NEJMoa1305584). Influenza A virus H7N9 emerged early in 2013, and human cases have continued to emerge since then. Although H7N9 virus-induced disease in humans is often very severe and even lethal, the majority of reported H7N9 cases occurred in older people and people with underlying medical conditions. To better understand the pathogenicity of this virus, healthy cynomolgus

  6. Could adult female acne be associated with modern life?

    PubMed

    Albuquerque, R G R; Rocha, M A D; Bagatin, E; Tufik, S; Andersen, M L

    2014-10-01

    In recent years, the prevalence of adult female acne has increased, but the reason for this increase remains unclear. Acne is one of the most common skin disorders. It can be triggered or worsened by endogenous and exogenous factors, including genetic predisposition, hormone concentrations, diet, smoke and stress; although the interaction with this last factor is not well understood. Modern life presents many stresses including urban noises, socioeconomic pressures and light stimuli. Women are especially affected by stress during daily routine. The recent insertion in the labor market is added to the duties of the mother and wife. Women also have a higher risk of developing psychiatric disorders such as depression and anxiety. Sleep restriction is added to these factors, with several negative consequences on health, including on hormonal secretion and the immune system. This is further complicated by the natural variation in sleep architecture across the menstrual cycle. Recent studies have brought new data about the mechanisms and possible factors involved. This review aims to establish a connection between stress, sleep deprivation and adult female acne.

  7. Evaluation of the phosphodiesterase 3 inhibitor ORG 9935 as a contraceptive in female macaques: initial trials.

    PubMed

    Jensen, Jeffrey T; Stouffer, Richard L; Stanley, Jessica E; Zelinski, Mary B

    2010-02-01

    The study was conducted to determine whether a phosphodiesterase (PDE) 3 inhibitor has potential as a novel contraceptive in primates. Regularly cycling adult female cynomolgus macaques of proven fertility (n=16) were treated for 7 months with placebo (controls) or the PDE3 inhibitor ORG 9935 as a daily food treat (150 mg/kg) or as a weekly depot injection (150 mg/kg, sc). After 1 month, a male of proven fertility was introduced into each group. Females underwent weekly monitoring of progesterone (P) and ultrasound evaluation for pregnancy if P remained elevated (1.0 ng/mL) >3 weeks. ORG 9935 values were evaluated using high-performance liquid chromatography. Overall, the pregnancy rate in ORG 9935-treated monkeys (4/8, 50%) did not differ from controls (7/8, 88%; p=.5). However, no animal became pregnant in a cycle when the serum level of ORG 9935 exceeded 300 nmol/L. Moreover, two treated monkeys who mated throughout the treatment phase and did not conceive became pregnant within four cycles after stopping ORG 9935. The other two animals were discontinued prematurely from the protocol. These results demonstrate that ORG 9935 may prevent pregnancy in primates at serum concentrations above 300 nmol/L and that the effect is reversible.

  8. Effect of neonatal ovariectomy and estradiol treatment on corticosterone release in response to stress in the adult female rat.

    PubMed

    McCormick, Cheryl M

    2011-01-01

    Although organizational effects of sex hormones in early life on hypothalamic-pituitary-adrenal function have been reported for males, the findings are mixed for females, likely the result of not controlling for adult gonadal status. In experiment 1, females were ovariectomized (OVX) either on postnatal day 1 or as adults and given estradiol benzoate (EB) and progesterone implants or not as adults. Corticosterone release in response to restraint stress was responsive to hormonal replacement irrespective of timing of OVX: without replacement, both OVX groups had lower corticosterone concentrations after restraint stress than did OVX groups with replacement and gonadally intact females. Thus, neonatal OVX did not alter the activational effects of sex hormones in adulthood. In a second experiment, females administered a dose of EB on postnatal day 1 had a more rapid decline of corticosterone concentrations after restraint as adults compared to oil-treated females, irrespective of whether they were OVX as neonates or as adults (all groups were given estradiol replacement as adults). Thus, evidently there are organizational effects of the sex hormonal milieu of the neonatal female, although this is a modest effect compared to previous reports in males.

  9. A Behavioral Comparison of Male and Female Adults with High Functioning Autism Spectrum Conditions

    PubMed Central

    Lai, Meng-Chuan; Lombardo, Michael V.; Pasco, Greg; Ruigrok, Amber N. V.; Wheelwright, Sally J.; Sadek, Susan A.; Chakrabarti, Bhismadev; Baron-Cohen, Simon

    2011-01-01

    Autism spectrum conditions (ASC) affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome). Of the 83 (45 males and 38 females) participants, 62 (33 males and 29 females) met Autism Diagnostic Interview-Revised (ADI-R) cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036), fewer current socio-communication difficulties (p = 0.001), and more self-reported autistic traits (p = 0.012) than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001), a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males. PMID:21695147

  10. Simian immunodeficiency virus SIVmac239 infection and simian human immunodeficiency virus SHIV89.6P infection result in progression to AIDS in cynomolgus macaques of Asian origin.

    PubMed

    Okamura, Tomotaka; Tsujimura, Yusuke; Soma, Shogo; Takahashi, Ichiro; Matsuo, Kazuhiro; Yasutomi, Yasuhiro

    2016-12-01

    Simian immunodeficiency virus (SIV) infection models in cynomolgus macaques are important for analysis of the pathogenesis of immunodeficiency virus and for studies on the efficacy of new vaccine candidates. However, very little is known about the pathogenesis of SIV or simian human immunodeficiency virus (SHIV) in cynomolgus macaques from different Asian countries. In the present study, we analysed the infectivity and pathogenicity of CCR5-tropic SIVmac and those of dual-tropic SHIV89.6P inoculated into cynomolgus macaques in Indonesian, Malaysian or Philippine origin. The plasma viral loads in macaques infected with either SIVmac239 or SHIV89.6P were maintained at high levels. CD4+ T cell levels in macaques infected with SIVmac239 gradually decreased. All of the macaques infected with SHIV89.6P showed greatly reduced CD4+ T-cell numbers within 6 weeks of infection. Eight of the 11 macaques infected with SIVmac239 were killed due to AIDS symptoms after 2-4.5 years, while four of the five macaques infected with SHIV89.6P were killed due to AIDS symptoms after 1-3.5 years. We also analysed cynomolgus macaques infected intrarectally with repeated low, medium or high doses of SIVmac239, SIVmac251 or SHIV89.6P. Infection was confirmed by quantitative RT-PCR at more than 5000, 300 and 500 TCID50 for SIVmac239, SIVmac251 and SHIV89.6P, respectively. The present study indicates that cynomolgus macaques of Asian origin are highly susceptible to SIVmac and SHIV infection by both intravenous and mucosal routes. These models will be useful for studies on virus pathogenesis, vaccination and therapeutics against human immunodeficiency virus/AIDS.

  11. REDUCTIONS IN CANNABIS USE ARE ASSOCIATED WITH MOOD IMPROVEMENT IN FEMALE EMERGING ADULTS.

    PubMed

    Moitra, Ethan; Anderson, Bradley J; Stein, Michael D

    2016-04-01

    Cannabis use and the development of depression symptoms have been linked in prospective research. However, no research has examined how depression symptoms might change relative to reductions in cannabis use. One group at risk for comorbid cannabis-use disorders and clinical depression is female emerging adults (those aged 18-25 years old) as cannabis use peaks during this period, depression is the most common psychiatric disorder among emerging adults, and females are at increased risk for depression relative to males. This study examined the longitudinal association between reductions in cannabis use and existing depression symptoms. Secondary analyses from a cannabis intervention trial for 332 female emerging adults were conducted. Changes in depression symptoms (categorized as minimal, mild, and moderate or more severe depression) were assessed in relation to changes in cannabis use at 3- and 6-months postbaseline assessment. After controlling for alcohol use, the association between change in cannabis-use frequency and change in depression (measured by Beck Depression Inventory-II) was significantly stronger for those with mild depression (b = -0.26; 95% CI: -0.44, -0.08; P = .004), and for those with moderate or more severe depression (b = -0.50; 95% CI: -0.68, -0.33; P < .001) relative to those with minimal depression. These results indicate a relationship between reductions in cannabis use and reductions in depression symptoms among female emerging adults who report at least mild depression symptoms. This represents a clinically meaningful effect for clinicians treating patients with co-occurring cannabis use and depressive disorders. © 2015 Wiley Periodicals, Inc.

  12. Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys.

    PubMed

    Yu, Rui; Fang, Ting; Liu, Shuling; Song, Xiaohong; Yu, Changming; Li, Jianmin; Fu, Ling; Hou, Lihua; Xu, Junjie; Chen, Wei

    2016-06-25

    Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine.

  13. Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys

    PubMed Central

    Yu, Rui; Fang, Ting; Liu, Shuling; Song, Xiaohong; Yu, Changming; Li, Jianmin; Fu, Ling; Hou, Lihua; Xu, Junjie; Chen, Wei

    2016-01-01

    Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine. PMID:27348002

  14. Female children with incarcerated adult family members at risk for lifelong neurological decline.

    PubMed

    Brewer-Smyth, Kathleen; Pohlig, Ryan T; Bucurescu, Gabriel

    2016-07-01

    A secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99 (60%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adulthood, especially related to traumatic brain injuries, compared to those without incarcerated adult family members. Along with being role models, adult family members impact the neurological health of children throughout their life-span.

  15. Regional fat distribution in adolescent and adult females with anorexia nervosa: A longitudinal study.

    PubMed

    El Ghoch, Marwan; Milanese, Chiara; Calugi, Simona; Müller, Manfred J; Pourhassan, Maryam; Ruocco, Antonella; Dalle Grave, Riccardo

    2015-12-01

    No study has yet compared body fat distribution before and after weight restoration in adolescent and adult patients with anorexia nervosa (AN) treated according to the same protocol. The study was set up to measure body fat distribution before and after short-term weight restoration in adolescent and adult patients with AN treated according to the same protocol in a specialist inpatient unit. We recruited 33 consecutive adolescent female patients with AN, and 33 controls matched by age and post-treatment BMI centile, as well as 33 adult female patients with AN, and 33 controls matched by age and post-treatment BMI. Dual-energy X-ray absorptiometry (DXA) was used to assess body composition before and after short-term weight restoration (BMI ≥ 18.5 kg/m²). Compared with controls, both adolescents and adults with AN showed that a greater amount of fat was lost from the extremities than the trunk before weight restoration, and that there was a central adiposity phenotype after short-term weight restoration. There were no significant differences in body fat distribution between adolescents and adults with AN before or after short-term weight restoration. Adolescent and adult females with AN have similar body fat distribution both before and after short-term weight restoration, and show a central adiposity phenotype after short-term weight restoration. The clinical implications of this finding are as yet unknown. Clinical Trials Registry- Regional Fat Distribution in Adolescent Girls and Adults with Anorexia Nervosa (ISRCTN73572502). Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  16. Depressive symptoms in older female carers of adults with intellectual disabilities.

    PubMed

    Chou, Y C; Pu, C-Y; Fu, L-Y; Kröger, T

    2010-12-01

    This survey study aims to examine the prevalence and factors associated with depressive symptoms among primary older female family carers of adults with intellectual disabilities (ID). In total, 350 female family carers aged 55 and older took part and completed the interview in their homes. The survey package contained standardised scales to assess carer self-reported depressive symptoms, social support, caregiving burden and disease and health, as well as adult and carer sociodemographic information. Multiple linear regressions were used to identify the factors associated with high depressive symptoms in carers. Between 64% and 72% of these carers were classified as having high depressive symptoms. The factors associated with carer self-reported depressive symptoms were carer physical health, social support and caregiving burden; overall, the carer self-reported physical health was a stronger factor associated with depressive symptoms than their physical disease status. The level of the adult with ID's behavioural functioning and the carer age, marital status, employment status, education level and the family income level were not significantly associated with carer depressive symptoms. The factors identified in this study as correlating with self-reported depressive symptoms suggest that researchers and mental health professionals should collaborate to help improve the physical health and social support networks of the most vulnerable older female family carers. This should reduce depressive symptoms directly among this high-risk group. © 2010 The Authors. Journal of Intellectual Disability Research © 2010 Blackwell Publishing Ltd.

  17. Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease.

    PubMed

    Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

    2008-05-01

    Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1-F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.

  18. Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

    PubMed Central

    Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

    2017-01-01

    Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1–F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8–E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1–F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1–F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states. PMID:18304984

  19. Long-term impacts of poaching on relatedness, stress physiology, and reproductive output of adult female african elephants.

    PubMed

    Gobush, K S; Mutayoba, B M; Wasser, S K

    2008-12-01

    Widespread poaching prior to the 1989 ivory ban greatly altered the demographic structure of matrilineal African elephant (Loxodonta africana) family groups in many populations by decreasing the number of old, adult females. We assessed the long-term impacts of poaching by investigating genetic, physiological, and reproductive correlates of a disturbed social structure resulting from heavy poaching of an African elephant population in Mikumi National Park, Tanzania, prior to 1989. We examined fecal glucocorticoid levels and reproductive output among 218 adult female elephants from 109 groups differing in size, age structure, and average genetic relatedness over 25 months from 2003 to 2005. The distribution in group size has changed little since 1989, but the number of families with tusked old matriarchs has increased by 14.2%. Females from groups that lacked an old matriarch, first-order adult relatives, and strong social bonds had significantly higher fecal glucocorticoid values than those from groups with these features (all females R(2)= 0.31; females in multiadult groups R(2)= 0.46). Females that frequented isolated areas with historically high poaching risk had higher fecal glucocorticoid values than those in low poaching risk areas. Females with weak bonds and low group relatedness had significantly lower reproductive output (R(2)[U]=0.21). Females from disrupted groups, defined as having observed average group relatedness 1 SD below the expected mean for a simulated unpoached family, had significantly lower reproductive output than females from intact groups, despite many being in their reproductive prime. These results suggest that long-term negative impacts from poaching of old, related matriarchs have persisted among adult female elephants 1.5 decades after the 1989 ivory ban was implemented.

  20. African American Female Adult Learners: Motivations, Challenges, and Coping Strategies.

    ERIC Educational Resources Information Center

    Coker, Angela D.

    2003-01-01

    Used data from a series of focus groups to examine the experiences of adult African American females in higher education. The article highlights participants' motivations, challenges, and sources of strength as they worked toward their academic goals. Women entered education for reasons over and beyond their own personal landscape. Their lives…

  1. The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schoenfeld, Heidi A., E-mail: heidi.schoenfeld@nov

    Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat didmore » not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50 mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p = 0.026), Aβ1-40 (35.2%; p = 0.04) and Aβtotal (29.8%; p = 0.04) acutely; this returned to normal as expected with repeated dosing for 15 days. CSF concentrations of newly generated Aβ (AUC{sub (0–24} {sub h)}) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p = 0.039) and day 15 (34.7%; p = 0.0003) and in shorter forms Aβ1-40 (23.4%; p = 0.009), Aβ1-38 (64.1%; p = 0.0001) and Aβtotal (50.45%; p = 0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300 mg/kg) or vehicle control for 39 weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the

  2. Simultaneous Assessment of Transporter-Mediated Drug-Drug Interactions Using a Probe Drug Cocktail in Cynomolgus Monkey.

    PubMed

    Kosa, Rachel E; Lazzaro, Sarah; Bi, Yi-An; Tierney, Brendan; Gates, Dana; Modi, Sweta; Costales, Chester; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena V

    2018-06-07

    We aim to establish an in vivo preclinical model to enable simultaneous assessment of inhibition potential of an investigational drug on clinically relevant drug transporters, organic anion transporting polypeptide (OATP)1B, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and organic anion transporter (OAT)3. Pharmacokinetics of substrate cocktail consisting of pitavastatin (OATP1B substrate), rosuvastatin (OATP1B/BCRP/OAT3), sulfasalazine (BCRP) and talinolol (P-gp) were obtained in cynomolgus monkey - alone or in combination with transporter inhibitors. Single dose rifampicin (30 mg/kg) significantly (p<0.01) increased the plasma exposure of all four drugs, with a marked effect on pitavastatin and rosuvastatin (AUC ratio ~21-39). Elacridar, BCRP/P-gp inhibitor, increased the AUC of sulfasalazine, talinolol, as well as rosuvastatin and pitavastatin. An OAT1/3 inhibitor (probenecid) significantly (p<0.05) impacted the renal clearance of rosuvastatin (~8-fold). In vitro, rifampicin (10μM) inhibited uptake of pitavastatin, rosuvastatin and sulfasalazine by monkey and human primary hepatocytes. Transport studies using membrane vesicles suggested that all probe substrates, except talinolol, are transported by cynoBCRP; while talinolol is a cynoP-gp substrate. Elacridar and rifampicin inhibited both cynoBCRP and cynoP-gp in vitro, indicating potential for in vivo intestinal efflux inhibition. In conclusion, a probe substrate cocktail was validated to simultaneously evaluate perpetrator impact on multiple clinically relevant transporters using the cynomolgus monkey. The results support the use of the cynomolgus monkey as a model that could enable drug-drug interaction risk assessment, before advancing a new molecular entity into clinical development, as well as providing mechanistic insights on transporter-mediated interactions. The American Society for Pharmacology and Experimental Therapeutics.

  3. A safety and immunogenicity study of immunization with hVEGF26-104/RFASE in cynomolgus monkeys.

    PubMed

    Wentink, Madelon Q; Verheul, Henk M W; Griffioen, Arjan W; Schafer, Kenneth A; McPherson, Susan; Early, Richard J; van der Vliet, Hans J; de Gruijl, Tanja D

    2018-04-05

    Vascular endothelial growth factor (VEGF) is pivotal in tumor angiogenesis and therapies targeting the VEGF axis are widely used in the clinic for the treatment of cancer. We have developed a therapeutic vaccine targeting human (h)VEGF 165 . hVEGF 26-104 /RFASE is based on the truncated protein hVEGF 26-104 as antigen formulated in an oil-in-water emulsion containing the sulpholipopolysaccharide RFASE as adjuvant. Here we describe the toxicity and immunogenicity of this therapeutic vaccine in cynomolgus monkeys. In total 54 cynomolgus monkeys were used and divided in 7 groups. Groups 1-3 were control groups, either receiving PBS alone (group 1), RFASE alone (group 2) or hVEGF 26-104 alone (group 3). Animals allocated to groups 4-7 received hVEGF 26-104 together with RFASE, but with varying doses of the antigen or the adjuvant. All animals were immunized four times with 2-week intervals and safety and immunogenicity were monitored until 3 days after the final immunization. Immunization induced an RFASE adjuvant dependent acute phase response. High titers of antibodies against hVEGF 26-104 and cross-reactive with hVEGF 165 , were found in monkey sera, 28 days after primer immunization. These antibodies were able to inhibit the binding of the monoclonal antibody bevacizumab with hVEGF 165 in a competition ELISA. Moreover, the biological activity of hVEGF 165 could be inhibited by the addition of immunized monkey serum in a VEGF specific bioassay. Importantly, no adverse events commonly observed with VEGF neutralization were observed throughout the study. These data show that hVEGF 26-104 /RFASE can be safely administered in cynomolgus monkeys, induces the desired immune response and therefore support the clinical development of this vaccine. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Disability, compensatory behavior, and innovation in free-ranging adult female Japanese macaques (Macaca fuscata).

    PubMed

    Turner, Sarah E; Fedigan, Linda M; Matthews, H Damon; Nakamichi, Masayuki

    2012-09-01

    Little is known about consequences of disability in nonhuman primates, yet individuals with disabilities can reveal much about behavioral flexibility, innovation, and the capabilities of a species. The Macaca fuscata population surrounding the Awajishima Monkey Center has experienced high rates of congenital limb malformation for at least 40 years, creating a unique opportunity to examine consequences of physical impairment in situ, in a relatively large sample of free-ranging adult monkeys. Here we present behavioral data on 11 disabled adult females and 12 nondisabled controls from 279 hours of randomly ordered 30-minute focal animal follows collected during May-August in 2005, 2006, and 2007. We quantified numerous statistically significant disability-related behavioral differences among females. Disabled females spent less time begging for peanuts from tourists, and employed a behavioral variant of such peanut begging; they had a lower frequency of hand use in grooming and compensated with increased direct use of the mouth or a two-arm pinch technique; and they had a higher frequency of self-scratching, and more use of feet in self-scratching. Self-scratching against substrates was almost exclusively a disability associated behavior. Two females used habitual bipedalism. These differences not withstanding, disabled females behaved similarly to controls in many respects: overall reliance on provisioned and wild foods, time spent feeding, and feeding efficiency did not differ among females, and there was no time difference in behavior performed arboreally or terrestrially. Disabled adult females were able to compensate behaviorally to perform social and life-sustaining activities, modifying existing behaviors to suit their individual physical situations and, occasionally, inventing new ways of doing things. © 2012 Wiley Periodicals, Inc.

  5. Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

    PubMed

    Bell, T M; Shaia, C I; Bunton, T E; Robinson, C G; Wilkinson, E R; Hensley, L E; Cashman, K A

    2015-01-01

    Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection. © The Author(s) 2014.

  6. Barriers, Motivations, and Preferences for Physical Activity Among Female African American Older Adults.

    PubMed

    Gothe, Neha P; Kendall, Bradley J

    2016-01-01

    According to the Centers for Disease Control and Prevention, less than 11% of adults more than the age of 65 meet the 2008 Physical Activity Guidelines for Americans. Among minority populations, only 5% of non-Hispanic Black older adults met the guidelines. Given our limited understanding of psychosocial and environmental factors that affect physical activity participation in these groups, the purpose of our focus groups was to investigate barriers, motivators, and preferences of physical activity for community-dwelling African American older adults. Three focus groups were conducted with female African American older adults ( N = 20). Questions posed to each focus group targeted motivations and barriers toward physical activity as well as their preferences for physical activity. The motivations included perceived health benefits of physical activity, social support, and enjoyment associated with engagement in physical activity. Prominent barriers included time and physical limitations, peer pressure and family responsibilities, and weather and poor neighborhood conditions. Group activities involving a dance component and novel exercises such as tai-chi or yoga were preferred choices. These findings should be taken into consideration when designing and implementing research or community physical activity programs for female African American older adults.

  7. Lepidium meyenii (Maca) increases litter size in normal adult female mice

    PubMed Central

    Ruiz-Luna, Ana C; Salazar, Stephanie; Aspajo, Norma J; Rubio, Julio; Gasco, Manuel; Gonzales, Gustavo F

    2005-01-01

    Background Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. Methods Adult female Balb/C mice were divided at random into three main groups: i) Reproductive indexes group, ii) Implantation sites group and iii) Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW) or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO) day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. Results Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. Conclusion Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to enhance female fertility. PMID

  8. Lepidium meyenii (Maca) increases litter size in normal adult female mice.

    PubMed

    Ruiz-Luna, Ana C; Salazar, Stephanie; Aspajo, Norma J; Rubio, Julio; Gasco, Manuel; Gonzales, Gustavo F

    2005-05-03

    Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. Adult female Balb/C mice were divided at random into three main groups: i) Reproductive indexes group, ii) Implantation sites group and iii) Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW) or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO) day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to enhance female fertility.

  9. Educating adult females for leadership roles in an informal science program for girls

    NASA Astrophysics Data System (ADS)

    McCreedy, Dale

    The purpose of this study is to gain an understanding of and an evidentiary warrant for, how a community of practice focused on informal science learning, can engage and promote active participation that offers adult female members and the community opportunities for legitimacy and transformation. This study is a qualitative, ethnographic research study that documents how adult female volunteers, historically inexperienced and/or excluded from traditional practices of science, come to engage in science activities through an informal, community-based context that helps them to appreciate science connections in their lives that are ultimately empowering and agentic. I begin to understand the ways in which such informal contexts, often thought to be marginal to dominant educational beliefs and practices, can offer adults outside of the field of science, education, or both, an entree into science learning and teaching that facilitate female's participation in legitimate and empowering ways. Using descriptive analyses, I first identify the characteristics of peripheral and active program participants. Through phenomenological analyses, I then develop an understanding of participation in an informal science program by focusing on three adult female members' unique trajectories of participation leading to core member status. Each draws on different aspects of the program that they find most salient, illustrating how different elements can serve as motivators for participation, and support continuation along the trajectory of participation reflecting personal and political agency. Through a purposeful ethnographic case-study analysis, I then explore one core member's transformation, evidenced by her developing identities as someone who enjoys science, engages in science activities, and, enacts a role as community old timer and door opener to science learning. This study: (1) contributes to the limited knowledge base in fields of informal learning, science education, and

  10. Weight-control behaviors and subsequent weight change among adolescents and young adult females123

    PubMed Central

    Haines, Jess; Rosner, Bernard; Willett, Walter C

    2010-01-01

    Background: Little is known about the effectiveness of behavioral strategies to prevent long-term weight gain among adolescents and young adults. Objective: The objective was to assess the relation of dietary and physical activity weight-control strategies, alone and together, with subsequent weight change. Design: This was a prospective study of 4456 female adolescents and young adults aged 14–22 y in the ongoing Growing Up Today Study. Weight-control behaviors, including dietary approaches and physical activity, were self-reported in 2001 and were used to predict weight change from 2001 to 2005. Results: In 2001–2002, 23.7% of female adolescents and young adults were trying to maintain their weight and another 54.4% were trying to lose weight. Approximately 25% used each of the following weight-control strategies: not eating snacks, following low-calorie or low-fat diets, and limiting portion sizes. In addition, 47.7% reported exercising at least occasionally for weight control. During 4 y of follow-up, participants gained an average of 3.3 kg. None of the dietary approaches to weight control predicted less weight change; however, females who exercised ≥5 d/wk gained significantly less weight than did their peers (−0.9 kg; 95% CI: −1.4, −0.4). The most successful strategy for weight-gain prevention among the females was to limit portion sizes (−1.9 kg; 95% CI: −2.6, −1.1) combined with frequent exercise. Conclusions: Our results suggest that physical activity is a necessary strategy for long-term weight control among adolescents and young adult females. Combining dietary weight-control approaches with physical activity is the most effective method for reducing weight gain. PMID:19889827

  11. Balancing Act: A Phenomenological Study of Female Adult Learners Who Successfully Persisted in Graduate Studies

    ERIC Educational Resources Information Center

    Shepherd, Jeff; Nelson, Barbara Mullins

    2012-01-01

    A study was conducted utilizing Cross' (1981) barriers to adult learning as a framework to better understand how adults successfully complete their graduate studies. Participants in the study were solicited via Facebook and LinkedIn. Three female adult learners who persisted in their graduate studies while balancing demands outside academics…

  12. Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque: a basic study for uterus transplantation.

    PubMed

    Kisu, Iori; Umene, Kiyoko; Adachi, Masataka; Emoto, Katsura; Nogami, Yuya; Banno, Kouji; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Narita, Hayato; Yoshida, Atsushi; Tsuchiya, Hideaki; Ogasawara, Kazumasa; Aoki, Daisuke

    2017-10-01

    How long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques? Warm ischemia in the uterus of cynomolgus macaques is tolerated for up to 4 h and reperfusion after uterine ischemia caused no further morphological and biochemical changes. Uterus transplantation is a potential option for women with uterine factor infertility. The allowable warm ischemic time and ischemia/reperfusion injury of the uterus in humans and non-human primates is unknown. This experimental study included 18 female cynomolgus macaques with periodic menstruation. Animals were divided into six groups of three monkeys each: a control group and groups with uterine ischemia for 0.5, 1, 2, 4 and 8 h. Biopsies of uterine tissues were performed before blood flow blockage, after each blockage time, and after reperfusion for 3 h. Blood sampling was performed after each blockage time, and after reperfusion for 5, 15 and 30 min for measurement of biochemical data. Resumption of menstruation was monitored after the surgical procedure. Morphological, physiological and biochemical changes after ischemia and reperfusion were evaluated. Mild muscle degeneration and zonal degeneration were observed in all animals subjected to warm ischemia for 4 or 8 h, but there were no marked differences in the appearance of specimens immediately after ischemia and after reperfusion for 3 h in animals subjected to 4 or 8 h of warm ischemia. There were no significant changes in any biochemical parameters at any time point in each group. Periodical menstruation resumed in all animals with warm ischemia up to 4 h, but did not recover in animals with warm ischemia for 8 h with atrophic uteri. Warm ischemia in actual transplantation was not exactly mimicked in this study because uteri were not perfused, cooled, transplanted or reanastomosed with vessels. Results in non-human primates cannot always be extrapolated to

  13. Pigeon paramyxovirus type 1 from a fatal human case induces pneumonia in experimentally infected cynomolgus macaques (Macaca fascicularis).

    PubMed

    Kuiken, Thijs; Buijs, Pascal; van Run, Peter; van Amerongen, Geert; Koopmans, Marion; van den Hoogen, Bernadette

    2017-11-21

    Although avian paramyxovirus type 1 is known to cause mild transient conjunctivitis in human beings, there are two recent reports of fatal respiratory disease in immunocompromised human patients infected with the pigeon lineage of the virus (PPMV-1). In order to evaluate the potential of PPMV-1 to cause respiratory tract disease, we inoculated a PPMV-1 isolate (hPPMV-1/Netherlands/579/2003) from an immunocompromised human patient into three healthy cynomolgus macaques (Macaca fascicularis) and examined them by clinical, virological, and pathological assays. In all three macaques, PPMV-1 replication was restricted to the respiratory tract and caused pulmonary consolidation affecting up to 30% of the lung surface. Both alveolar and bronchiolar epithelial cells expressed viral antigen, which co-localized with areas of diffuse alveolar damage. The results of this study demonstrate that PPMV-1 is a primary respiratory pathogen in cynomolgus macaques, and support the conclusion that PPMV-1 may cause fatal respiratory disease in immunocompromised human patients.

  14. Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles.

    PubMed

    Lei, Lei; Spradling, Allan C

    2013-05-21

    Whether or not mammalian females generate new oocytes during adulthood from germ-line stem cells to sustain the ovarian follicle pool has recently generated controversy. We used a sensitive lineage-labeling system to determine whether stem cells are needed in female adult mice to compensate for follicular losses and to directly identify active germ-line stem cells. Primordial follicles generated during fetal life are highly stable, with a half-life during adulthood of 10 mo, and thus are sufficient to sustain adult oogenesis without a source of renewal. Moreover, in normal mice or following germ-cell depletion with Busulfan, only stable, single oocytes are lineage-labeled, rather than cell clusters indicative of new oocyte formation. Even one germ-line stem cell division per 2 wk would have been detected by our method, based on the kinetics of fetal follicle formation. Thus, adult female mice neither require nor contain active germ-line stem cells or produce new oocytes in vivo.

  15. Pre-incubation with cyclosporine A potentiates its inhibitory effects on pitavastatin uptake mediated by recombinantly expressed cynomolgus monkey hepatic organic anion transporting polypeptide.

    PubMed

    Takahashi, Tsuyoshi; Ohtsuka, Tatsuyuki; Uno, Yasuhiro; Utoh, Masahiro; Yamazaki, Hiroshi; Kume, Toshiyuki

    2016-11-01

    Cyclosporine A, an inhibitor of hepatic organic anion transporting polypeptides (OATPs), reportedly increased plasma concentrations of probe substrates, although its maximum unbound blood concentrations were lower than the experimental half-maximal inhibitory (IC 50 ) concentrations. Pre-incubation with cyclosporine A in vitro before simultaneous incubation with probes has been reported to potentiate its inhibitory effects on recombinant human OATP-mediated probe uptake. In the present study, the effects of cyclosporine A and rifampicin on recombinant cynomolgus monkey OATP-mediated pitavastatin uptake were investigated in pre- and simultaneous incubation systems. Pre-incubation with cyclosporine A, but not with rifampicin, decreased the apparent IC 50 values on recombinant cynomolgus monkey OATP1B1- and OATP1B3-mediated pitavastatin uptake. Application of the co-incubated IC 50 values toward R values (1 + [unbound inhibitor] inlet to the liver, theoretically maximum /inhibition constant) in static models, 1.1 in monkeys and 1.3 in humans, for recombinant cynomolgus monkey and human OATP1B1-mediated pitavastatin uptake might result in the poor prediction of drug interaction magnitudes. In contrast, the lowered IC 50 values after pre-incubation with cyclosporine A provided better prediction with R values of 3.9 for monkeys and 2.7 for humans when the estimated maximum cyclosporine A concentrations at the inlet to the liver were used. These results suggest that the enhanced inhibitory potential of perpetrator medicines by pre-incubation on cynomolgus monkey OATP-mediated pitavastatin uptake in vitro could be of value for the precise estimation of drug interaction magnitudes in silico, in accordance with the findings from pre-administration of inhibitors on pitavastatin pharmacokinetics validated in monkeys. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Hybrid computational phantoms representing the reference adult male and adult female: construction and applications for retrospective dosimetry.

    PubMed

    Hurtado, Jorge L; Lee, Choonsik; Lodwick, Daniel; Goede, Timothy; Williams, Jonathan L; Bolch, Wesley E

    2012-03-01

    Currently, two classes of computational phantoms have been developed for dosimetry calculation: (1) stylized (or mathematical) and (2) voxel (or tomographic) phantoms describing human anatomy through mathematical surface equations and 3D voxel matrices, respectively. Mathematical surface equations in stylized phantoms are flexible, but the resulting anatomy is not as realistic. Voxel phantoms display far better anatomical realism, but they are limited in terms of their ability to alter organ shape, position, and depth, as well as body posture. A new class of computational phantoms called hybrid phantoms takes advantage of the best features of stylized and voxel phantoms-flexibility and anatomical realism, respectively. In the current study, hybrid computational phantoms representing the adult male and female reference anatomy and anthropometry are presented. These phantoms serve as the starting framework for creating patient or worker sculpted whole-body phantoms for retrospective dose reconstruction. Contours of major organs and tissues were converted or segmented from computed tomography images of a 36-y-old Korean volunteer and a 25-y-old U.S. female patient, respectively, with supplemental high-resolution CT images of the cranium. Polygon mesh models for the major organs and tissues were reconstructed and imported into Rhinoceros™ for non-uniform rational B-spline (NURBS) surface modeling. The resulting NURBS/polygon mesh models representing body contour and internal anatomy were matched to anthropometric data and reference organ mass data provided by Centers for Disease Control and Prevention and International Commission on Radiation Protection, respectively. Finally, two hybrid adult male and female phantoms were completed where a total of eight anthropometric data categories were matched to standard values within 4% and organ volumes matched to ICRP data within 1% with the exception of total skin. The hybrid phantoms were voxelized from the NURBS phantoms

  17. Radiosynthesis of the candidate beta-amyloid radioligand [(11)C]AZD2184: Positron emission tomography examination and metabolite analysis in cynomolgus monkeys.

    PubMed

    Andersson, Jan D; Varnäs, Katarina; Cselényi, Zsolt; Gulyás, Balázs; Wensbo, David; Finnema, Sjoerd J; Swahn, Britt-Marie; Svensson, Samuel; Nyberg, Svante; Farde, Lars; Halldin, Christer

    2010-10-01

    Beta-amyloid accumulation is associated with the pathogenesis of Alzheimer's disease (AD). AZD2184, a new radioligand for high-contrast positron emission tomography (PET) imaging of Abeta-deposits, has recently been developed and characterized in vitro and in rodents ex vivo. The objective of this study was to label AZD2184 with carbon-11, to perform in vivo characterization of [(11)C]AZD2184 ([(11)C]5) in the cynomolgus monkey brain as well as whole-body dosimetry, and to examine the metabolism of the labeled radioligand. [(11)C]5 was prepared by a two-step radiosynthesis starting with the reaction of 5-(6-(tert-butyldimethylsilyloxy)benzo[d]thiazol-2-yl)pyridin-2-amine with [(11)C]methyl iodide followed by deprotection using water. Four brain PET measurements in two cynomolgus monkeys and one whole-body PET measurement were performed with [(11)C]5. There was a high and rapid brain uptake (2.2-3.4% of injected dose at 2 min). The distribution of brain radioactivity was fairly uniform, with early to late-brain concentration ratios (peak vs. 60 min) higher for [(11)C]5 than ratios previously reported for [(11)C]PIB (8.2 and 4.6, respectively). Based on the whole-body data, it was estimated that an effective dose in an adult male would be 6.2 muSv/MBq and thus would be safe from a radiation point of view for multiple scans within the same year. [(11)C]5 shows binding characteristics, suggesting low levels of white-matter retention, and may thus provide improved contrast when compared with currently used PET radioligands for visualization of Abeta-deposits. On the basis of the labeling chemistry and the results of the biological evaluation, we conclude that [(11)C]5 should be useful for routine clinical studies. (c) 2010 Wiley-Liss, Inc.

  18. Are Males and Females Sexually Abused as Children Socially Anxious Adults?

    ERIC Educational Resources Information Center

    Rojas, Ariz; Kinder, Bill N.

    2009-01-01

    It is well documented that childhood sexual abuse is associated with deleterious outcomes in the areas of anxiety, depression, and sexual functioning. However, very little research has been conducted to specifically investigate childhood sexual abuse's relationship to adult social anxiety in both males and females. Participants included 250…

  19. Conversational Entrainment of Vocal Fry in Young Adult Female American English Speakers.

    PubMed

    Borrie, Stephanie A; Delfino, Christine R

    2017-07-01

    Conversational entrainment, the natural tendency for people to modify their behaviors to more closely match their communication partner, is examined as one possible mechanism modulating the prevalence of vocal fry in the speech of young American women engaged in spoken dialogue. Twenty young adult female American English speakers engaged in two spoken dialogue tasks-one with a young adult female American English conversational partner who exhibited substantial vocal fry and one with a young adult female American English conversational partner who exhibited quantifiably less vocal fry. Dialogues were analyzed for proportion of vocal fry, by speaker, and two measures of communicative success (efficiency and enjoyment). Participants employed significantly more vocal fry when conversing with the partner who exhibited substantial vocal fry than when conversing with the partner who exhibited quantifiably less vocal fry. Further, greater similarity between communication partners in their use of vocal fry tracked with higher scores of communicative efficiency and communicative enjoyment. Conversational entrainment offers a mechanistic framework that may be used to explain, to some degree, the frequency with which vocal fry is employed by young American women engaged in spoken dialogue. Further, young American women who modulated their vocal patterns during dialogue to match those of their conversational partner gained more efficiency and enjoyment from their interactions, demonstrating the cognitive and social benefits of entrainment. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  20. Assessment of early placental development in the cynomolgus monkey (Macaca fascicularis) using colour and pulsed wave Doppler sonography.

    PubMed

    Nimrod, C; Simpson, N; Hafner, T; de Vermette, R; Fournier, J; Coady, L; Baccanale, C

    1996-04-01

    Colour flow mapping and pulsed wave Doppler were used to assess the process of placental growth and development in the cynomolgus monkey from 32 to 71 days gestational age. Fetal and maternal vessels were reliably visualised and insonated. Accurate longitudinal non-invasive assessment of placentation is possible using this technique.

  1. Female children with incarcerated adult family members at risk for life-long neurological decline

    PubMed Central

    Brewer-Smyth, Kathleen; Pohlig, Ryan T.; Bucurescu, Gabriel

    2016-01-01

    A secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99(73%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adulthood, especially related to traumatic brain injuries, compared to those without incarcerated adult family members. Along with being role models, adult family members impact the neurological health of children throughout their lifespan. PMID:26788781

  2. Metabolism by conjugation appears to confer resistance to paracetamol (acetaminophen) hepatotoxicity in the cynomolgus monkey.

    PubMed

    Yu, Hong; Barrass, Nigel; Gales, Sonya; Lenz, Eva; Parry, Tony; Powell, Helen; Thurman, Dale; Hutchison, Michael; Wilson, Ian D; Bi, Luke; Qiao, Junwen; Qin, Qiuping; Ren, Jin

    2015-03-01

    1. Paracetamol overdose remains the leading cause of acute liver failure in humans. This study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. No adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. Only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals were observed, with no clear dose response. 3. Toxicokinetic analysis showed good plasma exposure, albeit with less than proportional rises in Cmax and AUC, with increasing dose. The Cmax values in monkey were up to 3.5 times those associated with human liver toxicity and the AUC approx. 1000 times those associated with liver enzyme changes in 31-44% of human subjects. 4. Metabolite profiling of urine by (1)H NMR spectroscopy revealed paracetamol and its glucuronide and sulphate metabolites. Glutathione-derived metabolites, e.g. the cysteinyl conjugate, were only present in very low concentrations whilst the mercapturate was not detected. 5. These in vivo observations demonstrated that the cynomolgus monkey is remarkably resistant to paracetamol-induced toxicity and a poor model for investigating paracetamol-related hepatotoxicity in humans.

  3. Female Reproductive Health After Childhood, Adolescent, and Young Adult Cancers: Guidelines for the Assessment and Management of Female Reproductive Complications

    PubMed Central

    Metzger, Monika L.; Meacham, Lillian R.; Patterson, Briana; Casillas, Jacqueline S.; Constine, Louis S.; Hijiya, Nobuko; Kenney, Lisa B.; Leonard, Marcia; Lockart, Barbara A.; Likes, Wendy; Green, Daniel M.

    2013-01-01

    Purpose As more young female patients with cancer survive their primary disease, concerns about reproductive health related to primary therapy gain relevance. Cancer therapy can often affect reproductive organs, leading to impaired pubertal development, hormonal regulation, fertility, and sexual function, affecting quality of life. Methods The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) are evidence-based recommendations for screening and management of late effects of therapeutic exposures. The guidelines are updated every 2 years by a multidisciplinary panel based on current literature review and expert consensus. Results This review summarizes the current task force recommendations for the assessment and management of female reproductive complications after treatment for childhood, adolescent, and young adult cancers. Experimental pretreatment as well as post-treatment fertility preservation strategies, including barriers and ethical considerations, which are not included in the COG-LTFU Guidelines, are also discussed. Conclusion Ongoing research will continue to inform COG-LTFU Guideline recommendations for follow-up care of female survivors of childhood cancer to improve their health and quality of life. PMID:23382474

  4. A Comparison of the Abuse Experiences of Male and Female Adults Molested as Children.

    ERIC Educational Resources Information Center

    Kendall-Tackett, Kathleen A.; Simon, Arthur F.

    To determine whether the molestation experiences of boys and girls differ, this study analyzed data from 365 adults (40 male and 325 female) molested as children, and compared findings for males and females on the identity of the perpetrator, age at onset and end of molestation, duration of molestation, type of sexual acts, and whether the…

  5. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

    PubMed Central

    Yano, Akira; Ito, Kaori; Miwa, Yoshikatsu; Kanazawa, Yoshito; Chiba, Akiko; Iigo, Yutaka; Kashimoto, Yoshinori; Kanda, Akira; Murata, Shinji; Makino, Mitsuhiro

    2015-01-01

    The reduction of brain amyloid beta (Aβ) peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer's disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ 40, and Aβ 42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ 40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies. PMID:26539559

  6. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs.

    PubMed

    Yano, Akira; Ito, Kaori; Miwa, Yoshikatsu; Kanazawa, Yoshito; Chiba, Akiko; Iigo, Yutaka; Kashimoto, Yoshinori; Kanda, Akira; Murata, Shinji; Makino, Mitsuhiro

    2015-01-01

    The reduction of brain amyloid beta (Aβ) peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer's disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ 40, and Aβ 42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ 40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.

  7. Causes of adult female deaths in Bangladesh: findings from two National Surveys.

    PubMed

    Nahar, Quamrun; El Arifeen, Shams; Jamil, Kanta; Streatfield, Peter Kim

    2015-09-18

    Assessment of causes of death and changes in pattern of causes of death over time are needed for programmatic purposes. Limited national level data exist on the adult female causes of death in Bangladesh. Using data from two nationally representation surveys, the 2001 and 2010 Bangladesh Maternal Mortality Surveys (BMMS), the paper examines the causes of adult female death, aged 15-49 years, and changes in the patterns of these deaths. In both surveys, all household deaths three years prior to the survey were identified. Adult female deaths were then followed by a verbal autopsy (VA) using the WHO structured questionnaire. Two physicians independently reviewed the VA forms to assign a cause of death using the ICD-10; in case of disagreement, a third physician made an independent review and assigned a cause of death. The overall mortality rates for women aged 15-49 in 2001 and 2010 were 182 per 100,000 and 120 per 100,000 respectively. There is a shift in the pattern of causes of death during the period covered by the two surveys. In the 2001 survey, the main causes of death were maternal (20 %), followed by diseases of the circulatory system (15 %), malignancy (14 %) and infectious diseases (13 %). However, in the 2010 survey, malignancies were the leading cause (21 %), followed by diseases of the circulatory system (16 %), maternal causes (14 %) and infectious diseases (8 %). While maternal deaths remained the number one cause of death among 20-34 years old in both surveys, unnatural deaths were the main cause for teenage deaths, and malignancies were the main cause of death for older women. Although there is an increasing trend in the proportion of women who died in hospitals, in both surveys most women died at home (74 % in 2001 and 62 % in 2010). The shift in the pattern of causes of adult female deaths is in agreement with the overall change in the disease pattern from communicable to non-communicable diseases in Bangladesh. Suicide and other violent deaths as

  8. The Role of Hox Genes in Female Reproductive Tract Development, Adult Function, and Fertility.

    PubMed

    Du, Hongling; Taylor, Hugh S

    2015-11-09

    HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Müllerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  9. HDRK-Woman: whole-body voxel model based on high-resolution color slice images of Korean adult female cadaver

    NASA Astrophysics Data System (ADS)

    Yeom, Yeon Soo; Jeong, Jong Hwi; Kim, Chan Hyeong; Han, Min Cheol; Ham, Bo Kyoung; Cho, Kun Woo; Hwang, Sung Bae

    2014-07-01

    In a previous study, we constructed a male reference Korean phantom; HDRK-Man (High-Definition Reference Korean-Man), to represent Korean adult males for radiation protection purposes. In the present study, a female phantom; HDRK-Woman (High-Definition Reference Korean-Woman), was constructed to represent Korean adult females. High-resolution color photographic images obtained by serial sectioning of a 26 year-old Korean adult female cadaver were utilized. The body height and weight, the skeletal mass, and the dimensions of the individual organs and tissues were adjusted to the reference Korean data. The phantom was then compared with the International Commission on Radiological Protection (ICRP) female reference phantom in terms of calculated organ doses and organ-depth distributions. Additionally, the effective doses were calculated using both the HDRK-Man and HDRK-Woman phantoms, and the values were compared with those of the ICRP reference phantoms.

  10. HDRK-Woman: whole-body voxel model based on high-resolution color slice images of Korean adult female cadaver.

    PubMed

    Yeom, Yeon Soo; Jeong, Jong Hwi; Kim, Chan Hyeong; Han, Min Cheol; Ham, Bo Kyoung; Cho, Kun Woo; Hwang, Sung Bae

    2014-07-21

    In a previous study, we constructed a male reference Korean phantom; HDRK-Man (High-Definition Reference Korean-Man), to represent Korean adult males for radiation protection purposes. In the present study, a female phantom; HDRK-Woman (High-Definition Reference Korean-Woman), was constructed to represent Korean adult females. High-resolution color photographic images obtained by serial sectioning of a 26 year-old Korean adult female cadaver were utilized. The body height and weight, the skeletal mass, and the dimensions of the individual organs and tissues were adjusted to the reference Korean data. The phantom was then compared with the International Commission on Radiological Protection (ICRP) female reference phantom in terms of calculated organ doses and organ-depth distributions. Additionally, the effective doses were calculated using both the HDRK-Man and HDRK-Woman phantoms, and the values were compared with those of the ICRP reference phantoms.

  11. Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication

    PubMed Central

    Amado, Luciane A; Marchevsky, Renato S; de Paula, Vanessa S; Hooper, Cleber; Freire, Marcos da S; Gaspar, Ana Maria C; Pinto, Marcelo A

    2010-01-01

    This work studied the replication sites of hepatitis A virus (HAV) in cynomolgus monkeys (Macaca fascicularis) after intravenous inoculation. The cynomolgus monkeys were inoculated with the Brazilian hepatitis A virus strain (HAF-203). Monkeys were euthanized on days 15, 30, 45 and 60 postinoculation (pi). Liver samples, submandibular salivary gland, mesenteric lymph node and tonsils were removed for virological and pathological evaluation. Immunofluorescence analyses on liver and salivary gland sections using confocal laser scanning microscopy revealed the presence of HAV antigen (HAV Ag). The presence of HAV genome was monitored by real-time PCR. The HAV RNA was detected at 7 days postinoculation (dpi), concomitantly in serum, saliva and faeces. The highest HAV viral load was observed in faeces at 15 dpi (105 copies/ml), followed by serum viral load of 104 copies/ml at 20 dpi and saliva viral load of 103copies/ml at 7 dpi. The animals showed first histological and biochemical signs of hepatitis at 15 dpi. The HAV antigen (Ag) was present from day 7 until day 60 pi in the liver and salivary glands. The HAV replicative intermediate was also detected in the liver (4.5 × 104 copies/mg), salivary glands (1.9 × 103 copies/mg), tonsils (4.2 × 101 copies/mg) and lymph nodes (3.4 × 101 copies/mg). Our data demonstrated that the salivary gland as an extrahepatic site of early HAV replication could create a potential risk of saliva transmitted infection. In addition, the cynomolgus monkey was confirmed as a suitable model to study the pathogenesis of HAV human infection. PMID:20096073

  12. Patient-specific FDG dosimetry for adult males, adult females, and very low birth weight infants

    NASA Astrophysics Data System (ADS)

    Niven, Erin

    Fluorodeoxyglucose is the most commonly used radiopharmaceutical in Positron Emission Tomography, with applications in neurology, cardiology, and oncology. Despite its routine use worldwide, the radiation absorbed dose estimates from FDG have been based primarily on data obtained from two dogs studied in 1977 and 11 adults (most likely males) studied in 1982. In addition, the dose estimates calculated for FDG have been centered on the adult male, with little or no mention of variations in the dose estimates due to sex, age, height, weight, nationality, diet, or pathological condition. Through an extensive investigation into the Medical Internal Radiation Dose schema for calculating absorbed doses, I have developed a simple patient-specific equation; this equation incorporates the parameters necessary for alterations to the mathematical values of the human model to produce an estimate more representative of the individual under consideration. I have used this method to determine the range of absorbed doses to FDG from the collection of a large quantity of biological data obtained in adult males, adult females, and very low birth weight infants. Therefore, a more accurate quantification of the dose to humans from FDG has been completed. My results show that per unit administered activity, the absorbed dose from FDG is higher for infants compared to adults, and the dose for adult women is higher than for adult men. Given an injected activity of approximately 3.7 MBq kg-1, the doses for adult men, adult women, and full-term newborns would be on the order of 5.5, 7.1, and 2.8 mSv, respectively. These absorbed doses are comparable to the doses received from other nuclear medicine procedures.

  13. Reemergence of Reston ebolavirus in Cynomolgus Monkeys, the Philippines, 2015.

    PubMed

    Demetria, Catalino; Smith, Ina; Tan, Titus; Villarico, Daniel; Simon, Edson Michael; Centeno, Rex; Tachedjian, Mary; Taniguchi, Satoshi; Shimojima, Masayuki; Miranda, Noel Lee J; Miranda, Mary Elizabeth; Rondina, Melissa Marie R; Capistrano, Rowena; Tandoc, Amado; Marsh, Glenn; Eagles, Debbie; Cruz, Ramses; Fukushi, Shuetsu

    2018-07-01

    In August 2015, a nonhuman primate facility south of Manila, the Philippines, noted unusual deaths of 6 cynomolgus monkeys (Macaca fascicularis), characterized by generalized rashes, inappetence, or sudden death. We identified Reston ebolavirus (RESTV) infection in monkeys by using serologic and molecular assays. We isolated viruses in tissues from infected monkeys and determined viral genome sequences. RESTV found in the 2015 outbreak is genetically closer to 1 of the 4 RESTVs that caused the 2008 outbreak among swine. Eight macaques, including 2 also infected with RESTV, tested positive for measles. Concurrently, the measles virus was circulating throughout the Philippines, indicating that the infection of the macaques may be a reverse zoonosis. Improved biosecurity measures will minimize the public health risk, as well as limit the introduction of disease and vectors.

  14. A novel disease affecting the predatory mite Phytoseiulus persimilis (Acari, Phytoseiidae): 2. Disease transmission by adult females.

    PubMed

    Schütte, Conny; Poitevin, Olivier; Negash, Tesfaye; Dicke, Marcel

    2006-01-01

    Adult female Phytoseiulus persimilis Athias-Henriot (Acari, Phytoseiidae) of one of our laboratory populations (=NR-population), show the following set of symptoms: predators shrink several days after mating, cease egg production and die several days after shrinking, show a lower degree of attraction to herbivore-induced plant volatiles and a shorter choice time in olfactometer tests, have the tendency to leave a prey patch with ample food, may carry excretory crystals in the legs, may cease prey consumption, and have a lower excretion rate. We hypothesized earlier that this characteristic syndrome, called non-responding (=NR-) syndrome, is caused by a pathogen infecting P. persimilis. To further support this hypothesis we here study several transmission modes of the factor causing the NR-syndrome. In all tests we measured size, short-term fecundity, mortality, predator position, response to plant odors and crystal location, thus including 6 of the 9 symptoms known yet. No evidence was found for vertical transmission from parent to offspring. Eggs from symptomatic females of the NR-population mated by males of the NR-population gave rise to normal-sized, well performing predators, when they had been surface sterilized or transferred to a new leaf. However, such eggs gave rise to shrunken females (17%) when left on the leaf where they had been laid. In the latter case transmission via products deposited on the leaf by the mothers was possible. We therefore tested several modes of horizontal transmission by exposing females of a commercial population that never showed the NR-syndrome (=R1-population) to products related to the symptomatic NR-population. No evidence was found for transmission via food or via squashed adult females. However, symptoms were induced in adult females of the R1-population after a 3-day exposure to a live adult female of the NR-population (incubation period=3-7 days, fraction shrunken females=53%) and after a 1-day exposure to feces and

  15. Developmental origins of neurotransmitter and transcriptome alterations in adult female zebrafish exposed to atrazine during embryogenesis.

    PubMed

    Wirbisky, Sara E; Weber, Gregory J; Sepúlveda, Maria S; Xiao, Changhe; Cannon, Jason R; Freeman, Jennifer L

    2015-07-03

    Atrazine is an herbicide applied to agricultural crops and is indicated to be an endocrine disruptor. Atrazine is frequently found to contaminate potable water supplies above the maximum contaminant level of 3μg/L as defined by the U.S. Environmental Protection Agency. The developmental origin of adult disease hypothesis suggests that toxicant exposure during development can increase the risk of certain diseases during adulthood. However, the molecular mechanisms underlying disease progression are still unknown. In this study, zebrafish embryos were exposed to 0, 0.3, 3, or 30μg/L atrazine throughout embryogenesis. Larvae were then allowed to mature under normal laboratory conditions with no further chemical treatment until 7 days post fertilization (dpf) or adulthood and neurotransmitter analysis completed. No significant alterations in neurotransmitter levels was observed at 7dpf or in adult males, but a significant decrease in 5-hydroxyindoleacetic acid (5-HIAA) and serotonin turnover was seen in adult female brain tissue. Transcriptomic analysis was completed on adult female brain tissue to identify molecular pathways underlying the observed neurological alterations. Altered expression of 1928, 89, and 435 genes in the females exposed to 0.3, 3, or 30μg/L atrazine during embryogenesis were identified, respectively. There was a high level of overlap between the biological processes and molecular pathways in which the altered genes were associated. Moreover, a subset of genes was down regulated throughout the serotonergic pathway. These results provide support of the developmental origins of neurological alterations observed in adult female zebrafish exposed to atrazine during embryogenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Patterns of Dating Violence Perpetration and Victimization in U.S. Young Adult Males and Females.

    PubMed

    Spencer, Rachael A; Renner, Lynette M; Clark, Cari Jo

    2016-09-01

    Dating violence (DV) is frequently reported by young adults in intimate relationships in the United States, but little is known about patterns of DV perpetration and victimization. In this study, we examined sexual and physical violence perpetration and victimization reported by young adults to determine how the violence patterns differ by sex and race/ethnicity. Data from non-Hispanic White, non-Hispanic Black, and Hispanic participants in Wave 3 of the National Longitudinal Study of Adolescent to Adult Health were analyzed. DV was assessed using responses to four questions focused on perpetration and four questions focused on victimization. The information on DV was taken from the most violent relationship reported by participants prior to Wave 3. Latent class analysis was first conducted separately by sex, adjusting for age, race/ethnicity, and financial stress, then by race/ethnicity, adjusting for age and financial stress. Relative model fit was established by comparing Bayesian Information Criteria (BIC), adjusted BIC, entropy, interpretability of latent classes, and certainty of latent class assignment for covariate-adjusted models. The results indicate that patterns of violence differed by sex and for females, by race/ethnicity. A three-class model was the best fit for males. For females, separate four-class models were parsimonious for White, Black, and Hispanic females. Financial stress was a significant predictor of violence classification for males and females and age predicted membership in White and Black female models. Variations in DV patterns by sex and race/ethnicity suggest the need for a more nuanced understanding of differences in DV. © The Author(s) 2015.

  17. White-tailed deer population dynamics and adult female survival in the presence of a novel predator: Deer Population Dynamics

    DOE PAGES

    Chitwood, Michael C.; Lashley, Marcus A.; Kilgo, John C.; ...

    2015-02-01

    Recent localized declines in white-tailed deer ( Odocoileus virginianus) populations in the southeastern United States have been linked to increasing predation pressure from coyotes ( Canis latrans), a novel predator to the region. Studies have documented coyotes as the leading cause of mortality for neonates, and 1 study documented coyotes as a mortality factor for adult females. However, no study has used field-based vital rates to conduct sensitivity analyses or model deer population trajectories under potential harvest or predator removal strategies. We used low, medium, and high values of fawn survival, adult female survival, and fecundity data collected from Fortmore » Bragg Military Installation, North Carolina to demonstrate the current declining population trajectory for deer (λ = 0.905; low λ = 0.788, high λ = 1.003). Consistent with other studies of ungulates, we determined adult female survival was the most sensitive and elastic vital rate. Further, for 3 potential management (“what if”) scenarios, we projected the population for 10 years using estimated vital rates. Reducing adult female harvest (λ = 0.935; low λ = 0.875, high λ = 1.002) and coyote removal (λ = 0.995; low λ = 0.898, high λ = 1.081) reduced the current population decline, whereas combining both approaches (λ = 1.024; low λ = 0.898, high λ = 1.141) resulted in population increases. Our data indicate that for low-density deer populations with heavy predation pressure on neonates, protecting adult females from harvest may not completely offset population declines. Coyote removal might be a necessary strategy because it could possibly increase very low fawn survival, which appears to be the most important vital rate influencing λ in our study. However, managers may have to start with reductions in adult female harvest because coyote removal would have to be continuous and consistently effective, making it an impractical management approach by itself.« less

  18. White-tailed deer population dynamics and adult female survival in the presence of a novel predator: Deer Population Dynamics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chitwood, Michael C.; Lashley, Marcus A.; Kilgo, John C.

    Recent localized declines in white-tailed deer ( Odocoileus virginianus) populations in the southeastern United States have been linked to increasing predation pressure from coyotes ( Canis latrans), a novel predator to the region. Studies have documented coyotes as the leading cause of mortality for neonates, and 1 study documented coyotes as a mortality factor for adult females. However, no study has used field-based vital rates to conduct sensitivity analyses or model deer population trajectories under potential harvest or predator removal strategies. We used low, medium, and high values of fawn survival, adult female survival, and fecundity data collected from Fortmore » Bragg Military Installation, North Carolina to demonstrate the current declining population trajectory for deer (λ = 0.905; low λ = 0.788, high λ = 1.003). Consistent with other studies of ungulates, we determined adult female survival was the most sensitive and elastic vital rate. Further, for 3 potential management (“what if”) scenarios, we projected the population for 10 years using estimated vital rates. Reducing adult female harvest (λ = 0.935; low λ = 0.875, high λ = 1.002) and coyote removal (λ = 0.995; low λ = 0.898, high λ = 1.081) reduced the current population decline, whereas combining both approaches (λ = 1.024; low λ = 0.898, high λ = 1.141) resulted in population increases. Our data indicate that for low-density deer populations with heavy predation pressure on neonates, protecting adult females from harvest may not completely offset population declines. Coyote removal might be a necessary strategy because it could possibly increase very low fawn survival, which appears to be the most important vital rate influencing λ in our study. However, managers may have to start with reductions in adult female harvest because coyote removal would have to be continuous and consistently effective, making it an impractical management approach by itself.« less

  19. Normal Anatomy, Histology, and Spontaneous Pathology of the Nasal Cavity of the Cynomolgus Monkey (Macaca fascicularis).

    PubMed

    Chamanza, Ronnie; Taylor, Ian; Gregori, Michela; Hill, Colin; Swan, Mark; Goodchild, Joel; Goodchild, Kane; Schofield, Jane; Aldous, Mark; Mowat, Vasanthi

    2016-07-01

    The evaluation of inhalation studies in monkeys is often hampered by the scarcity of published information on the relevant nasal anatomy and pathology. We examined nasal cavities of 114 control cynomolgus monkeys from 11 inhalation studies evaluated 2008 to 2013, in order to characterize and document the anatomic features and spontaneous pathology. Compared to other laboratory animals, the cynomolgus monkey has a relatively simple nose with 2 unbranched, dorsoventrally stacked turbinates, large maxillary sinuses, and a nasal septum that continues into the nasopharynx. The vomeronasal organ is absent, but nasopalatine ducts are present. Microscopically, the nasal epithelium is thicker than that in rodents, and the respiratory (RE) and transitional epithelium (TE) rest on a thick basal lamina. Generally, squamous epithelia and TE line the vestibule, RE, the main chamber and nasopharynx, olfactory epithelium, a small caudodorsal region, while TE is observed intermittently along the passages. Relatively high incidences of spontaneous pathology findings, some resembling induced lesions, were observed and included inflammation, luminal exudate, scabs, squamous and respiratory metaplasia or hyperplasia, mucous cell hyperplasia/metaplasia, and olfactory degeneration. Regions of epithelial transition were the most affected. This information is considered helpful in the histopathology evaluation and interpretation of inhalation studies in monkeys. © The Author(s) 2016.

  20. Serotonin signaling in the brain of adult female mice is required for sexual preference

    PubMed Central

    Zhang, Shasha; Liu, Yan; Rao, Yi

    2013-01-01

    A role for serotonin in male sexual preference was recently uncovered by our finding that male mutant mice lacking serotonin have lost sexual preference. Here we show that female mouse mutants lacking either central serotonergic neurons or serotonin prefer female over male genital odors when given a choice, and displayed increased female–female mounting when presented either with a choice of a male and a female target or only with a female target. Pharmacological manipulations and genetic rescue experiments showed that serotonin is required in adults. Behavioral changes caused by deficient serotonergic signaling were not due to changes in plasma concentrations of sex hormones. We demonstrate that a genetic manipulation reverses sexual preference without involving sex hormones. Our results indicate that serotonin controls sexual preference. PMID:23716677

  1. Pathogenesis of Lassa fever in cynomolgus macaques.

    PubMed

    Hensley, Lisa E; Smith, Mark A; Geisbert, Joan B; Fritz, Elizabeth A; Daddario-DiCaprio, Kathleen M; Larsen, Tom; Geisbert, Thomas W

    2011-05-06

    Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates. Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease. Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers. The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

  2. Orphaned female elephant social bonds reflect lack of access to mature adults.

    PubMed

    Goldenberg, Shifra Z; Wittemyer, George

    2017-10-31

    Compensatory social behavior in nonhuman animals following maternal loss has been documented, but understanding of how orphans allocate bonding to reconstruct their social networks is limited. Successful social integration may be critical to survival and reproduction for highly social species and, therefore, may be tied to population persistence. We examined the social partners involved in affiliative interactions of female orphans and non-orphans in an elephant population in Samburu, northern Kenya that experienced heightened adult mortality driven by drought and intense ivory poaching. We contrasted partners across different competitive contexts to gain insight to the influence of resource availability on social interactions. Though the number of partners did not differ between orphans and non-orphans, their types of social partners did. Orphans interacted with sisters and matriarchs less while feeding than did non-orphans, but otherwise their affiliates were similar. While resting under spatially concentrated shade, orphans had markedly less access to mature adults but affiliated instead with sisters, bulls, and age mates. Orphan propensity to strengthen bonds with non-dominant animals appears to offer routes to social integration following maternal loss, but lack of interaction with adult females suggests orphans may experience decreased resource access and associated fitness costs in this matriarchal society.

  3. Induction of pluripotent stem cells from a cynomolgus monkey using a polycistronic simian immunodeficiency virus-based vector, differentiation toward functional cardiomyocytes, and generation of stably expressing reporter lines.

    PubMed

    Wunderlich, Stephanie; Haase, Alexandra; Merkert, Sylvia; Beier, Jennifer; Schwanke, Kristin; Schambach, Axel; Glage, Silke; Göhring, Gudrun; Curnow, Eliza C; Martin, Ulrich

    2012-12-01

    Induced pluripotent stem cells (iPSCs) represent a novel cell source for regenerative therapies. Many emerging iPSC-based therapeutic concepts will require preclinical evaluation in suitable large animal models. Among the large animal species frequently used in preclinical efficacy and safety studies, macaques show the highest similarities to humans at physiological, cellular, and molecular levels. We have generated iPSCs from cynomolgus monkeys (Macaca fascicularis) as a segue to regenerative therapy model development in this species. Because typical human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors show poor transduction of simian cells, a simian immunodeficiency virus (SIV)-based vector was chosen for efficient transduction of cynomolgus skin fibroblasts. A corresponding polycistronic vector with codon-optimized reprogramming factors was constructed for reprogramming. Growth characteristics as well as cell and colony morphology of the resulting cynomolgus iPSCs (cyiPSCs) were demonstrated to be almost identical to cynomolgus embryonic stem cells (cyESCs), and cyiPSCs expressed typical pluripotency markers including OCT4, SOX2, and NANOG. Furthermore, differentiation in vivo and in vitro into derivatives of all three germ layers, as well as generation of functional cardiomyocytes, could be demonstrated. Finally, a highly efficient technique for generation of transgenic cyiPSC clones with stable reporter expression in undifferentiated cells as well as differentiated transgenic cyiPSC progeny was developed to enable cell tracking in recipient animals. In conclusion, our data indicate that cyiPSCs represent a valuable cell source for establishment of macaque-based allogeneic and autologous preclinical cell transplantation models for various fields of regenerative medicine.

  4. Spatial distribution of juvenile and adult female Tanner crabs (Chionoecetes bairdi) in a glacial fjord ecosystem: Implications for recruitment processes

    USGS Publications Warehouse

    Nielsen, J.K.; Taggart, S. James; Shirley, Thomas C.; Mondragon, Jennifer

    2007-01-01

    A systematic pot survey in Glacier Bay, Alaska, was conducted to characterize the spatial distribution of juvenile and adult female Tanner crabs, and their association with depth and temperature. The information was used to infer important recruitment processes for Tanner crabs in glaciated ecosystems. High-catch areas for juvenile and adult female Tanner crabs were identified using local autocorrelation statistics. Spatial segregation by size class corresponded to features in the glacial landscape: high-catch areas for juveniles were located at the distal ends of two narrow glacial fjords, and high-catch areas for adults were located in the open waters of the central Bay. Juvenile female Tanner crabs were found at nearly all sampled depths (15–439 m) and temperatures (4–8°C), but the biggest catches were at depths <150 m where adults were scarce. Because adults may prey on or compete with juveniles, the distribution of juveniles could be influenced by the distribution of adults. Areas where adults or predators are scarce, such as glacially influenced fjords, could serve as refuges for juvenile Tanner crabs.

  5. Immunotoxicological Evaluation of Genetically Modified Rice Expressing Cry1Ab/Ac Protein (TT51-1) by a 6-Month Feeding Study on Cynomolgus Monkeys

    PubMed Central

    Tan, Xiaoyan; Zhou, Xiaobing; Tang, Yao; Lv, Jianjun; Zhang, Lin; Sun, Li; Yang, Yanwei; Miao, Yufa; Jiang, Hua; Chen, Gaofeng; Huang, Zhiying; Wang, Xue

    2016-01-01

    The present study was performed to evaluate the food safety of TT51-1, a new type of genetically modified rice that expresses the Cry1Ab/Ac protein (Bt toxin) and is highly resistant to most lepidopteran pests. Sixteen male and 16 female cynomolgus monkeys were randomly divided into four groups: conventional rice (non-genetically modified rice, non-GM rice), positive control, 17.5% genetically modified rice (GM rice) and 70% GM rice. Monkeys in the non-GM rice, positive control, and GM rice groups were fed on diets containing 70% non-GM rice, 17.5% GM rice or 70% GM rice, respectively, for 182 days, whereas animals in the positive group were intravenously injected with cyclophosphamide every other day for a total of four injections before the last treatment. Six months of treatment did not yield abnormal observations. Specifically, the following parameters did not significantly differ between the non-GM rice group and GM rice groups: body weight, food consumption, electrocardiogram, hematology, immuno-phenotyping of lymphocytes in the peripheral blood, mitogen-induced peripheral blood lymphocyte proliferation, splenocyte proliferation, KLH-T cell-dependent antibody response, organ weights and ratios, and histological appearance (p>0.05). Animals from the GM rice group differed from animals in the non-GM rice group (p<0.05) in several parameters: specifically, their body temperatures and serum alanine aminotransferase (ALT) levels were higher, whereas their levels of serum K+, Cl- and cytokines (IL-2, IL-4 and IL-5) were lower. Because dose- or time-dependent changes were not observed in this study and animals appeared histologically normal, the aforementioned differences were not considered to be adverse or related to the treatment with GM rice. In conclusion, a 6-month feeding study of TT51-1 did not show adverse immunotoxicological effects on cynomolgus monkeys. PMID:27684490

  6. A toxicity profile of osteoprotegerin in the cynomolgus monkey.

    PubMed

    Smith, Brenda B; Cosenza, Mary Ellen; Mancini, Audrey; Dunstan, Colin; Gregson, Richard; Martin, Steven W; Smith, Susan Y; Davis, Harold

    2003-01-01

    Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (i.v.) or subcutaneous (s.c.) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [sALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated i.v. or s.c. at 15 mg/kg. Similar decreases were observed for sALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (i.v. or s.c.). Trabecular bone density was increased for the majority of males and females treated i.v. or s.c. at 15 mg/kg and males treated i.v. at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast

  7. Eating high fat chow enhances the locomotor-stimulating effects of cocaine in adolescent and adult female rats.

    PubMed

    Baladi, Michelle G; Koek, Wouter; Aumann, Megan; Velasco, Fortino; France, Charles P

    2012-08-01

    Dopamine systems vary through development in a manner that can impact drugs acting on those systems. Dietary factors can also impact the effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters locomotor effects of cocaine (1-56 mg/kg) in adolescent and adult female rats. Cocaine was studied in rats (n = 6/group) with free access to standard (5.7% fat) or high fat (34.3%) chow or restricted access to high fat chow (body weight matched to rats eating standard chow). After 1 week of eating high fat chow (free or restricted access), sensitivity to cocaine was significantly increased in adolescent and adult rats, compared with rats eating standard chow. Sensitivity to cocaine was also increased in adolescent rats with restricted, but not free, access to high fat chow for 4 weeks. When adolescent and adult rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. In adolescent and adult female rats eating high fat chow, but not those eating standard chow, sensitivity to cocaine increased progressively over once weekly tests with cocaine (i.e., sensitization) in a manner that was not statistically different between adolescents and adults. These results show that eating high fat chow alters sensitivity of female rats to acutely administered cocaine and also facilitates the development of sensitization to cocaine. That the type of food consumed can increase drug effects might have relevance to vulnerability to abuse cocaine in the female population.

  8. Measurements of female genital appearance in Chinese adults seeking genital cosmetic surgery: a preliminary report from a gynecological center.

    PubMed

    Cao, Yujiao; Li, Qiang; Zhou, Chuande; Li, Fengyong; Li, Senkai; Zhou, Yu

    2015-05-01

    Accurate and comprehensive measurements of the external genitalia in female adults are of great significance in surgery designs and for aesthetic evaluation in genital plastic surgeries. The authors carried out a 319-case study and provided baseline data and morphometric reference for plastic surgery involving the genital deformity caused by trauma or burns and male-to-female transsexual operations. Our study design recruited 319 women referred to the out-patient clinic from August 2010 to August 2013. From each individual we measured 16 parameters and assessed the significance of variations in age, height, weight, BMI, and marital status (as a proxy for parity). We tried to establish a female external genitalia database of the population presenting for cosmetic surgery and define the general proportions of female genitalia in Chinese adults from the data we obtained. A wide range of values was noted in female genital measurements especially in labia minora parameters. Four parameters, including clitoral prepuce length, clitoris to urethra, labial length, and perineal body length had a proportional relationship to some extent. The position of the clitoris and urethral orifice was found to be regular in female adults. Compared with unmarried women, perineal body length decreased (P = 0.048), while the apex to perineum (bilateral) and labial length increased (P = 0.005, 0.006, <0.0001) in those who were married. Several parameters were statistically significantly associated with age, height, weight, BMI, and marital status. We presented an external genitalia database of Chinese female adults asking for cosmetic surgery. Although the ranges of genital measurements vary, there is a proportional relationship in female genital appearance, which should be heeded in surgical designs and genital aesthetic evaluation.

  9. Effect of sericea lespedeza leaf meal pellets on adult female Haemonchus contortus in goats.

    PubMed

    Kommuru, D S; Whitley, N C; Miller, J E; Mosjidis, J A; Burke, J M; Gujja, S; Mechineni, A; Terrill, T H

    2015-01-15

    Sericea lespedeza (SL; Lespedeza cuneata) is a perennial warm-season forage rich in condensed tannins (CT) that has been reported to have anthelmintic activity against small ruminant gastrointestinal nematodes (GIN), particularly Haemonchus contortus, a highly pathogenic blood-feeder, but the mechanism of action of CT against H. contortus is not clearly understood. An experiment with young goats was designed to study the effect of SL leaf meal pellets on (1) a mature H. contortus infection, and (2) the surface appearance of adult H. contortus female worms. Thirty-six female and castrated male Boer crossbred goats artificially infected with H. contortus larvae were fed 75% SL leaf meal pellets or alfalfa pellets (18 goats/treatment group) in a 28-day confinement feeding trial. Fecal and blood samples were collected weekly for fecal egg count (FEC) and packed cell volume (PCV) determination, respectively, and all goats were slaughtered at the end of the trial for adult GIN recovery and counting. Five adult female H. contortus were recovered from the abomasum of two goats from each treatment group and from a prior study in which 75% and 95% SL leaf meal pellets or a commercial feed pellet were group-fed to grazing goats (270 days old, Spanish males, 10/treatment group) at 0.91 kg/head/d for 11 weeks. Adult GIN collected were fixed and examined for evidence of surface damage using scanning electron microscopy. Feeding 75% SL pellets to young goats in confinement reduced (P<0.05) FEC compared with control animals, while total worm numbers and PCV were not influenced by treatment. Three out of the 5 adult H. contortus recovered from SL treatment goats in the confinement feeding trial had cuticular surface damage, while no damage was observed on worms from the control group. All five worms observed from both SL treatments in the grazing study showed a shrunken, disheveled cuticular surface, whereas this was not observed on worms from control animals. Overall, this work

  10. Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

    PubMed

    Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

    2016-02-01

    Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Prepubertal exposure to bisphenol-A induces ERα upregulation and hyperplasia in adult gerbil female prostate

    PubMed Central

    Campos, Mônica S; Galvão, André L V; Rodríguez, Daniel A O; Biancardi, Manoel F; Marques, Mara R; Vilamaior, Patrícia S L; Santos, Fernanda C A; Taboga, Sebastião R

    2015-01-01

    Prostate physiology is highly dependent on oestrogenic and androgenic homeostasis. Interferences in this equilibrium, especially in early periods of life, may disrupt the prostate and increase the susceptibility to the development of diseases with ageing. Taking this into account, and considering the increase of environmental chemicals with endocrine-disrupting potential such as bisphenol-A (BPA), this study aimed to evaluate the prostates of adult female gerbils exposed to BPA and BPA plus testosterone from pubertal to adult periods. Morphological, stereological and chemical analyses revealed that long-term BPA exposure, even in environmental dosages, increases the proliferative status of the prostate, increases the number of ERα-positive stromal cells and elicits the development of prostatic hyperplasia in adult female gerbils. Moreover, we also observed that the association with testosterone did not increase the proliferative status of the gland, which shows that low levels of BPA are enough to cause an oestrogenic disruption of the prostate in young adults. This evidence suggests that this oestrogenic endocrine disruptor may increase the susceptibility to prostatic disorders with ageing. PMID:26098999

  12. Stimulus-Food Pairings Produce Stimulus-Directed Touch Screen Responding in Cynomolgus Monkeys ("Macaca Fascicularis") with or without a Positive Response Contingency

    ERIC Educational Resources Information Center

    Bullock, Christopher E.; Myers, Todd M.

    2009-01-01

    Acquisition and maintenance of touch-screen responding was examined in naive cynomolgus monkeys ("Macaca fascicularis") under automaintenance and classical conditioning arrangements. In the first condition of Experiment 1, we compared acquisition of screen touching to a randomly positioned stimulus (a gray square) that was either stationary or…

  13. Evaluation of a killed Rocky Mountain spotted fever vaccine in cynomolgus monkeys.

    PubMed Central

    Gonder, J C; Kenyon, R H; Pedersen, C E

    1979-01-01

    A nonhuman primate model of Rocky Mountain spotted fever infection was developed in cynomolgus monkeys (Macaca fascicularis) infected by the subcutaneous route or by aerosol. Clinical responses, hematology and serum chemistry values, and pathological findings were similar to those found in humans ill with Rocky Mountain spotted fever. The clinical model was then used to test the efficacy of a killed Rocky Mountain spotted fever vaccine grown in chicken embryo cells. Monkeys were immunized with varying dilutions of the vaccine with a two-dose schedule and then challenged at 2 months with virulent Rickettsia rickettsii by the subcutaneous route or by aerosol. The undiluted vaccine totally protected monkeys against both challenges, even at extremely high doses. PMID:120877

  14. Delayed Disease Progression in Cynomolgus Macaques Infected with Ebola Virus Makona Strain.

    PubMed

    Marzi, Andrea; Feldmann, Friederike; Hanley, Patrick W; Scott, Dana P; Günther, Stephan; Feldmann, Heinz

    2015-10-01

    In late 2013, the largest documented outbreak of Ebola hemorrhagic fever started in Guinea and has since spread to neighboring countries, resulting in almost 27,000 cases and >11,000 deaths in humans. In March 2014, Ebola virus (EBOV) was identified as the causative agent. This study compares the pathogenesis of a new EBOV strain, Makona, which was isolated in Guinea in 2014 with the prototype strain from the 1976 EBOV outbreak in the former Zaire. Both strains cause lethal disease in cynomolgus macaques with similar pathologic changes and hallmark features of Ebola hemorrhagic fever. However, disease progression was delayed in EBOV-Makona-infected animals, suggesting decreased rather than increased virulence of this most recent EBOV strain.

  15. Cloning of calves from various somatic cell types of male and female adult, newborn and fetal cows.

    PubMed

    Kato, Y; Tani, T; Tsunoda, Y

    2000-11-01

    Twenty-four calves were cloned from six somatic cell types of female and male adult, newborn and fetal cows. The clones were derived from female cumulus (n = 3), oviduct (n = 2) and uterine (n = 2) cells, female and male skin cells (n = 10), and male ear (n = 5) and liver (n = 2) cells. On the basis of the number of cloned embryos transferred (n = 172) to surrogate cows, the overall rate of success was 14%, but based on the number of surrogate mothers that became pregnant (n = 50), the success rate was 48%. Cell nuclei from uterus, ear and liver cells, which have not been tested previously, developed into newborn calves after nuclear transfer into enucleated oocytes. To date, seven female and six male calves have survived: six of the females were from adult cells (cumulus (n = 3), oviduct (n = 2) and skin (n = 1) cells) and one was from newborn skin cells, whereas the male calves were derived from adult ear cells (n = 3), newborn liver and skin cells (n = 2), and fetal cells (n = 1). Clones derived from adult cells frequently aborted in the later stages of pregnancy and calves developing to term showed a higher number of abnormalities than did those derived from newborn or fetal cells. The telomeric DNA lengths in the ear cells of three male calves cloned from the ear cells of a bull aged 10 years were similar to those of the original bull. However, the telomeric DNA lengths from the white blood cells of the clones, although similar to those in an age-matched control, were shorter than those of the original bull, which indicates that telomeric shortening varies among tissues.

  16. Sex at Sterkfontein: 'Mrs. Ples' is still an adult female.

    PubMed

    Grine, Frederick E; Weber, Gerhard W; Plavcan, J Michael; Benazzi, Stefano

    2012-05-01

    The important question of whether the Australopithecus africanus hypodigm is taxonomically heterogeneous revolves largely around the interpretation of the morphological variation exhibited by the fossils from Sterkfontein. The sex assignment of these specimens is a critical component in the evaluation of their morphological variability. The Sts 5 cranium is pivotal in this regard because it is the most complete and undistorted specimen attributed to A. africanus. Although it has traditionally been regarded as an adult female, this view has been challenged. In particular, it has been argued recently that Sts 5 is a juvenile and that this, together with alveolar bone loss that has supposedly reduced the size of the canine socket, has led to its misinterpretation as a female. Virtual reconstruction of the M(3) roots (and/or alveoli) contradicts arguments that these teeth were erupting at the time of death. Regardless, canine emergence and root completion are well ahead of M(3) development in juvenile australopiths from Sterkfontein. Thus, even if the M(3) root of Sts 5 was incomplete, its canine root would have been fully formed. Measurements of palate depth indicate that the alveolar margins of Sts 5 have not suffered from much (if any) bone loss in the region of the C/P(3); any additional bone would result in a palate of truly exceptional depth. Therefore, the dimensions of the canine alveolus of Sts 5 can be regarded as proxies for those of the canine root. The canine root of Sts 5 is among the smallest recorded for any Sterkfontein australopith, which provides strong support for Robert Broom's initial attribution of sex to this specimen. There is no evidence to contradict the assertion that 'Mrs. Ples' is an adult female. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Correlates of Serious Suicidal Ideation and Attempts in Female Adult Sexual Assault Survivors

    ERIC Educational Resources Information Center

    Ullman, Sarah E.; Najdowski, Cynthia J.

    2009-01-01

    Relations between (a) serious suicidal ideation and attempts and (b) demographics, trauma history, assault characteristics, post-assault outcomes, and psychosocial variables were examined among female adult sexual assault survivors. Younger, minority, and bisexual survivors reported greater ideation. More traumas, drug use, and assault disclosure…

  18. Retosiban Prevents Stretch-Induced Human Myometrial Contractility and Delays Labor in Cynomolgus Monkeys.

    PubMed

    Aye, Irving L M H; Moraitis, Alexandros A; Stanislaus, Dinesh; Charnock-Jones, D Stephen; Smith, Gordon C S

    2018-03-01

    Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies. To determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (1) the contractility of human myometrial explants and (2) labor in nonhuman primates. Human myometrial biopsies were obtained at planned term cesarean, and explants were exposed to stretch in the presence and absence of a range of drugs, including retosiban. The in vivo effects of retosiban were determined in cynomolgus monkeys. Prolonged mechanical stretch promoted myometrial extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Moreover, stretch-induced stimulation of myometrial contractility was prevented by ERK1/2 inhibitors. Retosiban (10 nM) prevented stretch-induced stimulation of myometrial contractility and phosphorylation of ERK1/2. Moreover, the inhibitory effect of retosiban on stretch-induced ERK1/2 phosphorylation was prevented by coincubation with a 100-fold excess of a peptide OTR antagonist, atosiban. Compared with vehicle-treated cynomolgus monkeys, treatment with oral retosiban (100 to 150 days of gestational age) reduced the risk of spontaneous delivery (hazard ratio = 0.07, 95% confidence interval 0.01 to 0.60, P = 0.015). The OTR acts as a uterine mechanosensor, whereby stretch increases myometrial contractility through agonist-free activation of the OTR. Retosiban prevents this through inverse agonism of the OTR and, in vivo, reduced the likelihood of spontaneous labor in nonhuman primates. We hypothesize that retosiban may be an effective preventative treatment of preterm birth in high-risk multiple pregnancies, an area of unmet clinical need.

  19. Effects of Early Smoking Habits on Young Adult Female Voices in Greece.

    PubMed

    Tafiadis, Dionysios; Toki, Eugenia I; Miller, Kevin J; Ziavra, Nausica

    2017-11-01

    Cigarette use is a preventable cause of mortality and diseases. The World Health Organization states that Europe and especially Greece has the highest occurrence of smoking among adults. The prevalence of smoking among women in Greece was estimated to be over 30% in 2012. Smoking is a risk factor for many diseases. Studies have demonstrated the association between smoking and laryngeal pathologies as well as changes in voice characteristics. The purpose of this study was to estimate the effect of early smoking habit on young adult female voices and if they perceive any vocal changes using two assessment methods. The Voice Handicap Index and the acoustic analyses of voice measurements were used, with both serving as mini-assessment protocols. Two hundred and ten young females (110 smokers and 100 nonsmokers) attending the Technological Educational Institute of Epirus in the School of Health and Welfare were included. Statistically significant increases for physical and total scores of the Voice Handicap Index were found in the smokers group (P < 0.05). Significant changes were observed for the acoustic parameters between smoker and nonsmoker groups. The results of this study indicated observable signs of change in the voice acoustic characteristics of young adults with early smoking habits. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  20. Improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model

    PubMed Central

    Araki, Susumu; Imai, Shinji; Ishigaki, Hirohito; Mimura, Tomohiro; Nishizawa, Kazuya; Ueba, Hiroaki; Kumagai, Kousuke; Kubo, Mitsuhiko; Mori, Kanji; Ogasawara, Kazumasa; Matsusue, Yoshitaka

    2015-01-01

    Background and purpose Integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. We investigated whether incorporation of mesenchymal stem cells (MSCs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. Methods Cynomolgus macaque bone marrow-derived MSCs were isolated and incorporated into type-I collagen gel. Full-thickness osteochondral defects (3 mm in diameter, 5 mm in depth) were created in the patellar groove of 36 knees of 18 macaques and were either left untreated (null group, n = 12), had collagen gel alone inserted (gel group, n = 12), or had collagen gel incorporating MSCs inserted (MSC group, n = 12). After 6, 12, and 24 weeks, the cartilage integration and tissue response were evaluated macroscopically and histologically (4 null, 4 gel, and 4 MSC knees at each time point). Results The gel group showed most cartilage-rich reparative tissue covering the defect, owing to formation of excessive cartilage extruding though the insufficient subchondral bone. Despite the fact that a lower amount of new cartilage was produced, the MSC group had better-quality cartilage with regular surface, seamless integration with neighboring naïve cartilage, and reconstruction of trabecular subchondral bone. Interpretation Even with intensive investigation, MSC-based cell therapy has not yet been established in experimental cartilage repair. Our model using cynomolgus macaques had optimized conditions, and the method using MSCs is superior to other experimental settings, allowing the possibility that the procedure might be introduced to future clinical practice. PMID:25175660

  1. Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques

    PubMed Central

    de Wit, Emmie; Rasmussen, Angela L.; Feldmann, Friederike; Bushmaker, Trenton; Martellaro, Cynthia; Haddock, Elaine; Okumura, Atsushi; Proll, Sean C.; Chang, Jean; Gardner, Don; Katze, Michael G.

    2014-01-01

    ABSTRACT In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277–2285, 2013, doi:10.1056/NEJMoa1305584). PMID:25118237

  2. Visible lesion laser thresholds in Cynomolgus (Macaca fascicularis) retina with a 1064 nm 12-ns pulsed laser

    NASA Astrophysics Data System (ADS)

    Oliver, Jeffrey W.; Stolarski, David J.; Noojin, Gary D.; Hodnett, Harvey M.; Imholte, Michelle L.; Rockwell, Benjamin A.; Kumru, Semih S.

    2007-02-01

    A series of experiments in a new animal model for retinal damage, cynomolgus monkeys (Macaca fascicularis), have been conducted to determine the damage threshold for 12.5-nanosecond laser exposures at 1064 nm. These results provide a direct comparison to threshold values obtained in rhesus monkey (Macaca mulatta), which is the model historically used in establishing retinal maximum permissible exposure (MPE) limits. In this study, the irradiance level of a collimated Gaussian laser beam of 2.5 mm diameter at the cornea was randomly varied to produce a rectangular grid of exposures on the retina. Exposures sites were fundoscopically evaluated at post-irradiance intervals of 1 hour and 24 hours. Probit analysis was performed on dose-response data to obtain probability of response curves. The 50% probability of damage (ED50) values for 1 and 24 hours post-exposure are 28.5(22.7-38.4) μJ and 17.0(12.9-21.8) μJ, respectively. These values compare favorably to data obtained with the rhesus model, 28.7(22.3-39.3) μJ and 19.1(13.6-24.4) μJ, suggesting that the cynomolgus monkey may be a suitable replacement for rhesus monkey in photoacoustic minimum visible lesion threshold studies.

  3. Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys.

    PubMed

    Ennulat, Daniela; Lynch, Karen M; Kimbrough, Carie L; Mirabile, Rosanna C; Rehm, Sabine

    2017-02-01

    Gastric mucosal injury is frequently observed in nonclinical studies of nonhuman primates. Because microscopic evaluation of stomach is generally a terminal procedure, our objective was to determine whether serum pepsinogen I (PG I) could serve as a noninvasive biomarker for detection of gastric mucosal injury in monkey. Serum PG I was measured using a commercial human immunoassay in cynomolgus monkeys ( n = 166) prior to dosing and/or terminally in 11 studies of up to 1 month duration. Mean ( SD) PG I values (ug/L) for monkeys with ( n = 59) and without ( n = 100) gastric mucosal degeneration were 101 (215) and 28 (12.6), respectively. For monkeys with baseline and terminal PG I data, mean ( SD) fold change (ratio of terminal to baseline PG I) for monkeys with ( n = 57) and without ( n = 76) glandular degeneration were 4.1 (11.3) and 1 (0.28). Receiver operating characteristic area under the curve (AUC) data demonstrated moderate diagnostic accuracy for serum PG I for glandular degeneration, AUC ( SE) 0.789 (0.04), with improved diagnostic accuracy as a fold change of baseline, AUC ( SE) 0.816 (0.04), consistent with the large interindividual but low intraindividual variability of serum PG I values in control monkeys. These data demonstrate that serum PG I is a useful biomarker of drug-induced gastric mucosal injury in the cynomolgus monkey.

  4. Effect of Perceived Stigmatisation on the Quality of Life among Ageing Female Family Carers: A Comparison of Carers of Adults with Intellectual Disability and Carers of Adults with Mental Illness

    ERIC Educational Resources Information Center

    Chou, Y. C.; Pu, C. Y.; Lee, Y. C.; Lin, L. C.; Kroger, T.

    2009-01-01

    Background: Little account has been taken of quality of life (QoL) among family carers of adults with an intellectual disability (ID) and family carers of adults with a mental illness (MI), particularly the female ageing carers' perceived stigma. We explore whether there are differences in the significant predictors of female ageing family carers'…

  5. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

    PubMed

    Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

    2018-05-02

    Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9

  6. Pathogenesis of lassa fever in cynomolgus macaques

    PubMed Central

    2011-01-01

    Background Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates. Methods Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease. Results Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers. Conclusion The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions. PMID:21548931

  7. Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

    PubMed Central

    Furuta, Miyako; Bridges, Robert S.

    2009-01-01

    The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

  8. Identification of individual adult female Javan lutungs (Trachypithecus auratus sondaicus) by using patterns of dark pigmentation in the pubic area.

    PubMed

    Tsuji, Yamato; Widayati, Kanthi Arum; Hadi, Islamul; Suryobroto, Bambang; Watanabe, Kunio

    2013-01-01

    In a series of field surveys of wild Javan lutungs (Trachypithecus auratus sondaicus) conducted at Pangandaran Nature Reserve in West Java, Indonesia, from 2011 to 2012, we tried to use a method of individual identification by using individual-specific patterns of dark pigmentation in the pubic area. During the 2011 dry season, we used a digital SLR camera with a 400-mm telephoto lens to photograph the pubic area of each individual of a habituated group. These photographs were the basis for identifying 14 different adult females. During the rainy season of 2011 and the dry season of 2012, we checked the presence/absence of each of the identified individuals and found that these patterns were stable, at least during our study period. We found that two adult females and one adult female disappeared from the subject group between the first and second and between the second and third surveys, respectively, and that one adult female gave birth between the first and second surveys, but the infant had disappeared from the group between the second and third surveys. We could not confirm the validity of the method for juvenile females because of the dense white hair in their pubic areas and the fact that few individuals had clear patterns. Furthermore, we could not use this method for males because of the lack of pigmentation in the pubic area. As patterns of pigmentation in the pubic area are known to be present in other Trachypithecus species, our method can be useful for identification of individual adult females of these species, on which few individual-based behavioral studies have been conducted. Collecting individual-based behavioral data would enable us to track the presence of individuals in groups or movements between groups; determine the effects of social rank and age on within-group competition and copulation; and examine population data.

  9. Muscle wasting associated with pathologic change is a risk factor for the exacerbation of joint swelling in collagen-induced arthritis in cynomolgus monkeys

    PubMed Central

    2013-01-01

    Background Not only joint destruction but also muscle wasting due to rheumatoid cachexia has been problem in terms of quality of life of patients with rheumatoid arthritis (RA). In the present study, we performed histopathological examination and assessed relationships between characteristic parameters relating to muscle and joint swelling in a collagen-induced arthritis (CIA) model using cynomolgus monkeys (CMs). Methods Female CMs were used and CIA was induced by twice immunizations using bovine type II collagen with Freund’s complete adjuvant. Arthritis level was evaluated from the degree of swelling at the peripheral joints of the fore and hind limbs. Food consumption, body weight, and serum biochemical parameters were measured sequentially. Five or 6 animals per time point were sacrificed at 2, 3, 5 and 9 weeks after the first immunization to obtain quadriceps femoris specimens for histopathology. Pimonidazole hydrochloride was intravenously administered to determine tissue hypoxia in skeletal muscle. Results Gradual joint swelling was observed and the maximum arthritis score was noted at Week 5. In histopathology, necrosis of muscle fiber in the quadriceps femoris was observed only at Week 2 and the most significant findings such as degeneration, atrophy, and regeneration of muscle fiber were mainly observed at Week 5. Food consumption was decreased up to Week 4 but recovered thereafter. Body weight decreased up to Week 5 and did not completely recover thereafter. A biphasic increase in serum cortisol was also observed at Weeks 2 and 5. Histopathology showed that muscle lesions were mainly composed of degeneration and atrophy of the muscle fibers, and ATPase staining revealed that the changes were more pronounced in type II muscle fiber than type I muscle fiber. In the pimonidazole experiment, mosaic pattern in skeletal muscle was demonstrated in the intact animal, but not the CIA animal. Increased arthritis score was accompanied by a decrease in serum

  10. Transgender identity development as represented by a group of female-to-male transgendered adults.

    PubMed

    Morgan, Sarah W; Stevens, Patricia E

    2008-06-01

    This article represents work done in the discipline of nursing to raise awareness about the lives and experiences of transgendered persons, who receive little coverage in our nursing textbooks, professional journals, or student clinical experiences. The findings presented here are from a larger qualitative examination of the lives and experiences of a group of 11 transgendered adults that examined four broad areas: transgender identity recognition, acknowledgement, and development; bodily experiences; relationships with others; and health care experiences. The focus of this article is the relevant findings related to four participants in the study who identified as female-to-male (FTM), meaning they were born female-bodied, but identify as male. The highlight here is on the recognition, acknowledgement, and development of transgender identity. Our intention is to expose uninformed people to first-hand accounts by FTM transgendered persons about their life trajectories, particularly during childhood, adolescence, and the early adult years.

  11. Rare male aggression directed toward females in a female-dominated society: Baiting behavior in the spotted hyena

    USGS Publications Warehouse

    Szykman, Micaela; Engh, Anne L.; Van Horn, Russell C.; Boydston, Erin E.; Scribner, Kim T.; Holekamp, Kay E.

    2003-01-01

    Spotted hyenas (Crocuta crocuta) are gregarious carnivores. The females are socially dominant to males, and adult males rarely direct aggression toward adult females. This study analyzed all cases in which adult immigrant males behaved aggressively toward adult females in a large population of free-living hyenas in Kenya, observed for 11 years. Our goals were to describe the conditions under which male attacks on females occur, and address possible adaptive functions. Most aggression directed by adult immigrant males against females occurred when coalitions of two or more males attacked a single adult female, who typically responded by defending herself and fighting back. Male aggression against females frequently occurred at sites of ungulate kills, but males never behaved aggressively toward females over food, and all male attacks on females were unprovoked. Although no mounting or other copulatory behaviors ever occurred during or immediately after an attack, the number of male attacks on females peaked around the time of conception. Daily rates at which males attacked females did not vary with female social rank. However, daily attack rates did vary significantly with female reproductive state, and the highest rates of male attack on females were observed during the two stages of the reproductive cycle during which females were most likely to conceive litters. The adaptive significance of male aggression against females in this species remains unknown, but a tight association between male attacks on females and a female's time of conception provides strong evidence of some role for male aggression in hyena sexual behavior. In particular, our data are consistent with hypotheses suggesting that male aggression toward females in this species either serves to inform females about male fitness or represents sexual harassment.

  12. Social bonds in the dispersing sex: partner preferences among adult female chimpanzees.

    PubMed

    Foerster, Steffen; McLellan, Karen; Schroepfer-Walker, Kara; Murray, Carson M; Krupenye, Christopher; Gilby, Ian C; Pusey, Anne E

    2015-07-01

    In most primate societies, strong and enduring social bonds form preferentially among kin, who benefit from cooperation through direct and indirect fitness gains. Chimpanzees, Pan troglodytes , differ from most species by showing consistent female-biased dispersal and strict male philopatry. In most East African populations, females tend to forage alone in small core areas and were long thought to have weak social bonds of little biological significance. Recent work in some populations is challenging this view. However, challenges remain in quantifying the influence of shared space use on association patterns, and in identifying the drivers of partner preferences and social bonds. Here, we use the largest data set on wild chimpanzee behaviour currently available to assess potential determinants of female association patterns. We quantify pairwise similarities in ranging, dyadic association and grooming for 624 unique dyads over 38 years, including 17 adult female kin dyads. To search for social preferences that could not be explained by spatial overlap alone, we controlled for expected association based on pairwise kernel volume intersections of core areas. We found that association frequencies among females with above-average overlap correlated positively with grooming rates, suggesting that associations reflected social preferences in these dyads. Furthermore, when available, females preferred kin over nonkin partners for association and grooming, and variability was high among nonkin dyads. While variability in association above and below expected values was high, on average, nonkin associated more frequently if they had immature male offspring, while having female offspring had the opposite effect. Dominance rank, an important determinant of reproductive success at Gombe, influenced associations primarily for low-ranking females, who associated preferentially with each other. Our findings support the hypothesis that female chimpanzees form well

  13. Assessment of the Protective Effect of Imvamune and Acam2000 Vaccines against Aerosolized Monkeypox Virus in Cynomolgus Macaques

    PubMed Central

    Graham, Victoria A.; Bewley, Kevin R.; Dennis, Mike; Taylor, Irene; Funnell, Simon G. P.; Bate, Simon R.; Steeds, Kimberley; Tipton, Thomas; Bean, Thomas; Hudson, Laura; Atkinson, Deborah J.; McLuckie, Gemma; Charlwood, Melanie; Roberts, Allen D. G.; Vipond, Julia

    2013-01-01

    To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed. There was no significant difference (P > 0.05) between the levels of neutralizing antibody in animals vaccinated with a single immunization of Acam2000 (132 U/ml) and the prime-boost Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost Imvamune group, whereas there was no confirmation of excreted live virus in the Acam2000 group. This evaluation of different human smallpox vaccines in cynomolgus macaques helps to provide information about optimal vaccine strategies in the absence of human challenge studies. PMID:23658452

  14. Smoking topography and abstinence in adult female smokers

    PubMed Central

    McClure, Erin A.; Saladin, Michael E.; Baker, Nathaniel L.; Carpenter, Matthew J.; Gray, Kevin M.

    2013-01-01

    Preliminary evidence, within both adults and adolescents, suggests that the intensity with which cigarettes are smoked (i.e. smoking topography) is predictive of success during a cessation attempt. These reports have also shown topography to be superior compared to other variables, such as cigarettes per day, in the prediction of abstinence. The possibility that gender may influence this predictive relationship has not been evaluated, but may be clinically useful in tailoring gender-specific interventions. Within the context of a clinical trial for smoking cessation among women, adult daily smokers completed a laboratory session that included a 1-hour ad-libitum smoking period in which measures of topography were collected (N=135). Participants were then randomized to active medication (nicotine patch vs. varenicline) and abstinence was monitored for 4 weeks. Among all smoking topography measures and all abstinence outcomes, a moderate association was found between longer puff duration and greater puff volume and continued smoking during the active 4-week treatment phase, but only within the nicotine patch group. Based on the weak topography-abstinence relationship among female smokers found in the current study, future studies should focus on explicit gender comparisons to examine if these associations are specific to or more robust in male smokers. PMID:24018226

  15. Smoking topography and abstinence in adult female smokers.

    PubMed

    McClure, Erin A; Saladin, Michael E; Baker, Nathaniel L; Carpenter, Matthew J; Gray, Kevin M

    2013-12-01

    Preliminary evidence, within both adults and adolescents, suggests that the intensity with which cigarettes are smoked (i.e., smoking topography) is predictive of success during a cessation attempt. These reports have also shown topography to be superior compared to other variables, such as cigarettes per day, in the prediction of abstinence. The possibility that gender may influence this predictive relationship has not been evaluated but may be clinically useful in tailoring gender-specific interventions. Within the context of a clinical trial for smoking cessation among women, adult daily smokers completed a laboratory session that included a 1-hour ad libitum smoking period in which measures of topography were collected (N=135). Participants were then randomized to active medication (nicotine patch vs. varenicline) and abstinence was monitored for 4weeks. Among all smoking topography measures and all abstinence outcomes, a moderate association was found between longer puff duration and greater puff volume and continued smoking during the active 4-week treatment phase, but only within the nicotine patch group. Based on the weak topography-abstinence relationship among female smokers found in the current study, future studies should focus on explicit gender comparisons to examine if these associations are specific to or more robust in male smokers. © 2013 Elsevier Ltd. All rights reserved.

  16. A longitudinal analysis of circulating stress-related proteins and chronic ethanol self-administration in cynomolgus macaques

    PubMed Central

    Helms, Christa M.; Messaoudi, Ilhem; Jeng, Sophia; Freeman, Willard M.; Vrana, Kent E.; Grant, Kathleen A.

    2011-01-01

    Background Alcoholics have alterations in endocrine and immune function and increased susceptibility to stress-related disorders. A longitudinal analysis of chronic ethanol intake on homeostatic mechanisms is, however, incompletely characterized in primates. Methods Plasma proteins (n = 60; Luminex) and hormones (adrenocorticotropic hormone, ACTH; cortisol) were repeatedly measured in adult male cynomolgus monkeys (Macaca fascicularis, n = 10) during a 32-month experimental protocol at baseline, during induction of water and ethanol (4% w/v in water) self-administration, after 4 months and after 12 months of 22-h daily concurrent access to ethanol and water. Results Significant changes were observed in ACTH, cortisol and 45/60 plasma proteins: a majority (28/45) were suppressed as a function of ethanol self-administration, eight proteins were elevated and nine showed biphasic changes. Cortisol and ACTH were greatest during induction, and correlations between these hormones and plasma proteins varied across the experiment. Pathway analyses implicated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) as possible mediators of ethanol-induced effects on immune-related proteins in primates. Conclusion Chronic ethanol consumption in primates leads to an allostatic state of physiological compromise with respect to circulating immune- and stress-related proteins in NF-κB- and STAT/JAK-related pathways in correlation with altered endocrine activity. PMID:22141444

  17. Female Adult Aedes albopictus Suppression by Wolbachia-Infected Male Mosquitoes.

    PubMed

    Mains, James W; Brelsfoard, Corey L; Rose, Robert I; Dobson, Stephen L

    2016-09-23

    Dengue, chikungunya and zika viruses are pathogens with an increasing global impact. In the absence of an approved vaccine or therapy, their management relies on controlling the mosquito vectors. But traditional controls are inadequate, and the range of invasive species such as Aedes albopictus (Asian Tiger Mosquito) is expanding. Genetically modified mosquitoes are being tested, but their use has encountered regulatory barriers and public opposition in some countries. Wolbachia bacteria can cause a form of conditional sterility, which can provide an alternative to genetic modification or irradiation. It is unknown however, whether openly released, artificially infected male Ae. albopictus can competitively mate and sterilize females at a level adequate to suppress a field population. Also, the unintended establishment of Wolbachia at the introduction site could result from horizontal transmission or inadvertent female release. In 2014, an Experimental Use Permit from the United States Environmental Protection Agency approved a pilot field trial in Lexington, Kentucky, USA. Here, we present data showing localized reduction of both egg hatch and adult female numbers. The artificial Wolbachia type was not observed to establish in the field. The results are discussed in relation to the applied use of Wolbachia-infected males as a biopesticide to suppress field populations of Ae. albopictus.

  18. The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration

    PubMed Central

    Neal, Alice; Boldrin, Luisa; Morgan, Jennifer Elizabeth

    2012-01-01

    Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. We have investigated age and sex differences between mouse satellite cells in vitro and assessed the importance of these factors as mediators of donor cell engraftment in an in vivo model of satellite cell transplantation. We found that satellite cell numbers are increased in growing compared to adult and in male compared to female adult mice. We saw no difference in the expression of the myogenic regulatory factors between male and female mice, but distinct profiles were observed according to developmental stage. We show that, in contrast to adult mice, the majority of satellite cells from two week old mice are proliferating to facilitate myofibre growth; however a small proportion of these cells are quiescent and not contributing to this growth programme. Despite observed changes in satellite cell populations, there is no difference in engraftment efficiency either between satellite cells derived from adult or pre-weaned donor mice, male or female donor cells, or between male and female host muscle environments. We suggest there exist two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration. PMID:22662253

  19. Sex differences in adults' relative visual interest in female and male faces, toys, and play styles.

    PubMed

    Alexander, Gerianne M; Charles, Nora

    2009-06-01

    An individual's reproductive potential appears to influence response to attractive faces of the opposite sex. Otherwise, relatively little is known about the characteristics of the adult observer that may influence his or her affective evaluation of male and female faces. An untested hypothesis (based on the proposed role of attractive faces in mate selection) is that most women would show greater interest in male faces whereas most men would show greater interest in female faces. Further, evidence from individuals with preferences for same-sex sexual partners suggests that response to attractive male and female faces may be influenced by gender-linked play preferences. To test these hypotheses, visual attention directed to sex-linked stimuli (faces, toys, play styles) was measured in 39 men and 44 women using eye tracking technology. Consistent with our predictions, men directed greater visual attention to all male-typical stimuli and visual attention to male and female faces was associated with visual attention to gender conforming or nonconforming stimuli in a manner consistent with previous research on sexual orientation. In contrast, women showed a visual preference for female-typical toys, but no visual preference for male faces or female-typical play styles. These findings indicate that sex differences in visual processing extend beyond stimuli associated with adult sexual behavior. We speculate that sex differences in visual processing are a component of the expression of gender phenotypes across the lifespan that may reflect sex differences in the motivational properties of gender-linked stimuli.

  20. Tissue Mercury Concentrations and Survival of Tree Swallow Embryos, Nestlings and Young Adult Females on a Contaminated Site.

    PubMed

    Taylor, Capwell E; Cristol, Daniel A

    2015-10-01

    Tree swallows nesting on mercury-contaminated sites along the South River in Virginia, USA were monitored for reproductive success. The bodies of nestlings found deceased in their nest boxes were collected, along with blood and feather samples from the adult parents and surviving siblings. We also measured hatching and fledging success of the clutches and the annual recapture rate of adults. We found that the body feathers of deceased nestlings contained significantly higher concentrations of mercury (12.89 ± 8.42 μg/g, n = 15) than those of nestlings that survived to fledge (7.41 ± 4.79 μg/g, n = 15). However, mothers of more successful clutches (>75 % hatching) did not differ in mercury concentrations from females with less successful clutches (<50 % hatching). Additionally, adult females breeding for the first time that returned to breed the following year did not differ in blood mercury from females of the same age that bred once but never returned. Our results suggest that mercury had its greatest effect on these songbirds during the nestling stage, whereas for embryos or first-time breeding females, other factors likely played larger roles in mortality.

  1. Seasonal variation in telencephalon cell proliferation in adult female tsinling dwarf skinks (Scincella tsinlingensis).

    PubMed

    Yang, Chun; Wang, Limin; Xing, Xiangyang; Gao, Yanyan; Guo, Li

    2017-05-01

    In adult mammals, neurogenesis is limited to specific niches in the brain, but considerable adult neurogenesis occurs in many brain regions in non-mammalian vertebrates. Non-mammalian vertebrates provide invaluable comparative material for understanding the core mechanisms of adult neural stem cell maintenance and fate, but phylogenetic differences in adult neurogenesis remain poorly understood. Here we examine cell proliferation seasonality in the telencephalon of adult female tsinling dwarf skinks (Scincella tsinlingensis) by injecting wild animals caught in summer, autumn and spring, and animals caught in autumn and raised under winter conditions, with 5-Bromo-2'-deoxyuridine (BrdU). Then, 24h, 7d and 28d after BrdU administration we examined brain tissue and quantified BrdU-labeled cells as a marker of neuronal proliferation. The highest number of labeled cells in the telencephalon was found in the 7d group. BrdU-positive cells were widely distributed in the anterior olfactory nucleus (AON), medial cortex (MC), dorsal cortex (DC), lateral cortex (LC), dorsal ventricular ridge (DVR), septum (SP), striatum (STR) and nucleus sphericus (NS). No BrdU-positive cells were detected in olfactory bulbs or elsewhere in the telencephalon. The highest proliferative levels were found in the AON in autumn. The NS exhibited relatively high levels of cell proliferation. The proliferative rate in the AON fluctuated seasonally as autumn>summer>spring>winter. Glial fibrillary acidic protein-positive cells were widely distributed in the telencephalon and their fibrous processes extended into brain parenchyma and anchored in the meninges. Doublecortin-positive newborn neurons of the subventricular zone appeared to migrate into the cerebral cortex via the radial migratory stream. Cell proliferation in the telencephalon of adult female S. tsinlingensis fluctuates seasonally, especially in regions related to olfactory memory. This is the first demonstration of proliferative activity in

  2. The Experiences and Needs of Female Adults with High-Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Baldwin, Susanna; Costley, Debra

    2016-01-01

    There is limited large-scale research into the lived experiences of female adults who have an autism spectrum disorder with no co-occurring intellectual disability. Drawing on the findings of an Australia-wide survey, this report presents self-report data from n = 82 women with high-functioning autism spectrum disorder in the areas of health,…

  3. The experience of high-frequency gambling behavior of older adult females in the United Kingdom: An interpretative phenomenological analysis.

    PubMed

    Pattinson, Julie; Parke, Adrian

    2017-01-01

    The prevalence of older adult female gambling participation and gambling disorder is increasing in the UK, and there is a paucity of published research available to understand possible risk factors for frequent gambling in this demographic. The aim of the current study was to identify and explore motivations and patterns of gambling behavior in high-frequency older adult female gamblers in the UK, from the perspective of the individual and in the context of their experience of aging. Ten UK older adult female high-frequency gamblers were recruited via stratified purposive sampling, with a mean age of 70.4 years. Data was collected via semistructured interviews and analyzed using interpretative phenomenological analysis. Three core themes representative of the experience of this phenomenon emerged from the transcripts, including: Filling voids, emotional escape, and overspending. The present study has provided a contextualized understanding of motivating factors and several age-related vulnerabilities that may account for high gambling frequency in this population.

  4. Neurosteroids in Adult Hippocampus of Male and Female Rodents: Biosynthesis and Actions of Sex Steroids.

    PubMed

    Hojo, Yasushi; Kawato, Suguru

    2018-01-01

    The brain is not only the target of steroid hormones but also is able to locally synthesize steroids de novo . Evidence of the local production of steroids in the brain has been accumulating in various vertebrates, including teleost fish, amphibia, birds, rodents, non-human primates, and humans. In this review, we mainly focus on the local production of sex steroids in the hippocampal neurons of adult rodents (rats and mice), a center for learning and memory. From the data of the hippocampus of adult male rats, hippocampal principal neurons [pyramidal cells in CA1-CA3 and granule cells in dentate gyrus (DG)] have a complete system for biosynthesis of sex steroids. Liquid chromatography with tandem-mass-spectrometry (LC-MS/MS) enabled us to accurately determine the levels of hippocampal sex steroids including 17β-estradiol (17β-E2), testosterone (T), and dihydrotestosterone (DHT), which are much higher than those in blood. Next, we review the steroid synthesis in the hippocampus of female rats, since previous knowledge had been biased toward the data from males. Recently, we clarified that the levels of hippocampal steroids fluctuate in adult female rats across the estrous cycle. Accurate determination of hippocampal steroids at each stage of the estrous cycle is of importance for providing the account for the fluctuation of female hippocampal functions, including spine density, long-term potentiation (LTP) and long-term depression (LTD), and learning and memory. These functional fluctuations in female had been attributed to the level of circulation-derived steroids. LC-MS/MS analysis revealed that the dendritic spine density in CA1 of adult female hippocampus correlates with the levels of hippocampal progesterone and 17β-E2. Finally, we introduce the direct evidence of the role of hippocampus-synthesized steroids in hippocampal function including neurogenesis, LTP, and memory consolidation. Mild exercise (2 week of treadmill running) elevated synthesis of DHT

  5. Association between mandibular retrognathia and TMJ disorders in adult females.

    PubMed

    Miller, James R; Burgess, Jeffrey A; Critchlow, Cathy W

    2004-01-01

    This study assesses the association between temporomandibular joint (TMJ) disorders and mandibular retrognathia. We conducted a case-control study among women, aged 18-70 years, recruited from Kaiser Permanente Northwest Division (KPNW, Portland, OR) and Group Health Cooperative of Puget Sound (GHC, Seattle, WA). Cases (N= 160) were women seeking treatment for TMJ disorders at KPNW and GHC clinics. Controls (N=151) were women without TMJ disorders, selected from among adult female dental hygiene patients at KPNW or GHC enrollees. Case status was determined by questionnaire; mandibular sagittal position (orthognathic, mildly retrognathic, severely retrognathic, or prognathic) was measured using digitized facial photographs. Odds ratios (OR) and associated 95 percent confidence intervals (CI) estimated the magnitude of the association between TMJ disorders and mandibular sagittal position. Women with TMJ disorders were 4.0 times (95% CI=1.5, 10.8) more likely than controls to have severe retrognathia; no association with mild retrognathia or prognathia was seen. Results were similar when cases were restricted to those with recent onset of TMJ pain (OR=6.3; 95% CI=1.8, 21.8). We found a strong association between TMJ disorders and severe mandibular retrognathia in adult females. In some women this likely resulted from TMJ disorders influencing mandibular development over time. However, among a subset of women, our data support the reverse hypothesis--that severe mandibular retrognathia may influence the development of TMJ disorders. Despite this strong association, abnormal mandibular position contributed only a small portion to the overall rate at which women sought treatment for TMJ disorders.

  6. Preclinical Evaluation of an Anti-Nectin-4 ImmunoPET Reagent in Tumor-Bearing Mice and Biodistribution Studies in Cynomolgus Monkeys.

    PubMed

    Campbell, Dean O; Noda, Akihiro; Verlinsky, Alla; Snyder, Josh; Fujita, Yuji; Murakami, Yoshihiro; Fushiki, Hiroshi; Miyoshi, Sosuke; Lacayo, Sergio; Cabral, Edward; Yang, Peng; Stover, David R; Joseph, Ingrid B J K

    2016-10-01

    Nectin-4 is selectively overexpressed in a variety of cancers and is currently under clinical investigation as a therapeutic target. A monoclonal antibody against nectin-4 (AGS-22M6) was evaluated as an Immuno-positron emission tomography (ImmunoPET) reagent. Its ability to assay nectin-4 expression as well as detect nectin-4 positive tumors in the liver and bone was evaluated using mouse models. The biodistribution of [(89)Zr]AGS-22M6 was evaluated in mice bearing tumors with varying levels of nectin-4 expression. An isogenic breast cancer tumor line was used to model metastatic liver and bone disease in mice. The biodistribution of [(18)F]AGS-22M6 in cynomolgus monkeys was evaluated. A positive correlation was demonstrated between tumor nectin-4 expression and [(89)Zr]AGS-22M6 uptake. Tumors in the liver and bone were detected and differentiated based on nectin-4 expression. [(18)F]AGS-22M6 showed limited uptake in cynomolgus monkey tissues. [(89)Zr]AGS-22M6 is a promising ImmunoPET reagent that can assay nectin-4 expression in both primary and metastatic lesions.

  7. Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring

    PubMed Central

    La Merrill, Michele; Karey, Emma; Moshier, Erin; Lindtner, Claudia; La Frano, Michael R.; Newman, John W.; Buettner, Christoph

    2014-01-01

    Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring. PMID:25076055

  8. Differential Effects of Family Structure on Religion and Spirituality of Emerging Adult Males and Females.

    PubMed

    Handal, Paul J; Lace, John W

    2017-08-01

    This study examined measures of religion and spirituality in a sample of male and female emerging adult college students whose parents were either divorced or intact using the Personal Religious Inventory, the Duke University Religion Index, the Daily Spiritual Experiences Scale, the Spiritual Transcendence Scale, and the Spiritual Involvement and Beliefs Scale. Data were collected online, and 66% of participants received extra credit for participating. A main effect of sex was found, as females reported significantly higher scores than men on all but one measure of religion and spirituality, and the dataset was separated by sex. No differences were found between males from divorced and intact families. However, females from intact families scored significantly higher on all religion and spirituality measures than females from divorced families. This study suggests that females may respond differently than males to their parents' divorce in the context of religion and spirituality, and discusses possible reasons.

  9. Prenatal Testosterone Exposure Decreases Aldosterone Production but Maintains Normal Plasma Volume and Increases Blood Pressure in Adult Female Rats.

    PubMed

    More, Amar S; Mishra, Jay S; Hankins, Gary D; Kumar, Sathish

    2016-08-01

    Plasma testosterone levels are elevated in pregnant women with preeclampsia and polycystic ovaries; their offspring are at increased risk for hypertension during adult life. We tested the hypothesis that prenatal testosterone exposure induces dysregulation of the renin-angiotensin-aldosterone system, which is known to play an important role in water and electrolyte balance and blood pressure regulation. Female rats (6 mo old) prenatally exposed to testosterone were examined for adrenal expression of steroidogenic genes, telemetric blood pressure, blood volume and Na(+) and K(+) levels, plasma aldosterone, angiotensin II and vasopressin levels, and vascular responses to angiotensin II and arg(8)-vasopressin. The levels of Cyp11b2 (aldosterone synthase), but not the other adrenal steroidogenic genes, were decreased in testosterone females. Accordingly, plasma aldosterone levels were lower in testosterone females. Plasma volume and serum and urine Na(+) and K(+) levels were not significantly different between control and testosterone females; however, prenatal testosterone exposure significantly increased plasma vasopressin and angiotensin II levels and arterial pressure in adult females. In testosterone females, mesenteric artery contractile responses to angiotensin II were significantly greater, while contractile responses to vasopressin were unaffected. Angiotensin II type-1 receptor expression was increased, while angiotensin II type-2 receptor was decreased in testosterone arteries. These results suggest that prenatal testosterone exposure downregulates adrenal Cyp11b2 expression, leading to decreased plasma aldosterone levels. Elevated angiotensin II and vasopressin levels along with enhanced vascular responsiveness to angiotensin II may serve as an underlying mechanism to maintain plasma volume and Na(+) and K(+) levels and mediate hypertension in adult testosterone females. © 2016 by the Society for the Study of Reproduction, Inc.

  10. Childhood Sexual Abuse as a Predictor of Adult Female Sexual Dysfunction: A Study of Couples Seeking Sex Therapy.

    ERIC Educational Resources Information Center

    Sarwer, David B.; Durlak, Joseph A.

    1996-01-01

    A study of 359 married women who sought sex therapy with their spouses found a connection between adult female sexual dysfunction and childhood sexual abuse. Abuse involving sexual penetration was specifically associated with adult sexual dysfunction. Future research on additional variables that contribute to sexual dysfunction is urged. (CR)

  11. Assessment of ixekizumab, an interleukin-17A monoclonal antibody, for potential effects on reproduction and development, including immune system function, in cynomolgus monkeys.

    PubMed

    Clarke, D O; Hilbish, K G; Waters, D G; Newcomb, D L; Chellman, G J

    2015-12-01

    The reproductive and developmental toxicity of ixekizumab, a selective inhibitor of interleukin-17A (IL-17A), was assessed in the following studies in cynomolgus monkeys: fertility (3-month dosing), embryo-fetal development (EFD; dosing from gestation day (GD) 20 through 139), and pre-postnatal development (PPND; dosing from GD 20 through parturition). Because IL-17A has functional roles in innate and humoral immunity, immune system modulation was evaluated in the EFD and PPND studies; immunological evaluations in infants comprised peripheral blood immunophenotyping, Natural Killer cell cytolytic activity, and T-cell-dependent antibody (IgG and IgM) primary and secondary responses to antigen challenge. Ixekizumab exposure was sustained during the dosing periods in most adult monkeys. Fetal exposure at Cesarean section (GD 140-142; EFD study) was 18-25% of maternal exposure and ixekizumab was present in infants for up to 29 weeks postpartum. There were no adverse effects attributed to ixekizumab in any study. Importantly, immune system development and maturation were unaffected. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Gut transcriptome of replete adult female cattle ticks, Rhipicephalus (Boophilus) microplus, feeding upon a Babesia bovis-infected bovine host.

    PubMed

    Heekin, Andrew M; Guerrero, Felix D; Bendele, Kylie G; Saldivar, Leo; Scoles, Glen A; Dowd, Scot E; Gondro, Cedric; Nene, Vishvanath; Djikeng, Appolinaire; Brayton, Kelly A

    2013-09-01

    As it feeds upon cattle, Rhipicephalus (Boophilus) microplus is capable of transmitting a number of pathogenic organisms, including the apicomplexan hemoparasite Babesia bovis, a causative agent of bovine babesiosis. The R. microplus female gut transcriptome was studied for two cohorts: adult females feeding on a bovine host infected with B. bovis and adult females feeding on an uninfected bovine. RNA was purified and used to generate a subtracted cDNA library from B. bovis-infected female gut, and 4,077 expressed sequence tags (ESTs) were sequenced. Gene expression was also measured by a microarray designed from the publicly available R. microplus gene index: BmiGI Version 2. We compared gene expression in the tick gut from females feeding upon an uninfected bovine to gene expression in tick gut from females feeding upon a splenectomized bovine infected with B. bovis. Thirty-three ESTs represented on the microarray were expressed at a higher level in female gut samples from the ticks feeding upon a B. bovis-infected calf compared to expression levels in female gut samples from ticks feeding on an uninfected calf. Forty-three transcripts were expressed at a lower level in the ticks feeding upon B. bovis-infected female guts compared with expression in female gut samples from ticks feeding on the uninfected calf. These array data were used as initial characterization of gene expression associated with the infection of R. microplus by B. bovis.

  13. Postpartum immobilization of adult female moose using xylazine, ketamine and yohimbine hydrochlorides.

    PubMed

    Garner, D L; Addison, E M

    1994-01-01

    Twenty-two free-ranging adult female moose (Alces alces) were immobilized with a 1:4 mixture of xylazine hydrochloride (XH) and ketamine hydrochloride (KH). Mean (SD) dosages/animal for XH and KH were 419 (148) and 1565 (433) mg, respectively. Mean (SD) induction time was 18.4 (9.7) minutes. Reversal with yohimbine hydrochloride using a mean dosage of 83 mg/animal resulted in a mean (SD) recovery time of 22.8 (28.5) minutes.

  14. Adult Female and Male Siblings of Persons with Disabilities: Findings from a National Survey

    ERIC Educational Resources Information Center

    Hodapp, Robert M.; Urbano, Richard C.; Burke, Meghan M.

    2010-01-01

    In this study, the authors used a national, Web-based survey to examine female and male siblings of individuals with disabilities. More than 1,160 adult siblings completed a 163-question survey about themselves, their siblings, and their sibling relationships. Most respondents reported fairly close contact with their siblings and positive sibling…

  15. Use of Q methodology to assess the concerns of adult female individuals seeking orthodontic treatment

    PubMed Central

    Yao, Linjie; Xu, Xingqiao; Ni, Zhenyu; Zheng, Minling; Lin, Feiou

    2015-01-01

    Background Orthodontic treatment may cause functional restrictions, discomfort, and pain, which may lead to dental anxiety and noncooperation among patients. This study aimed to assess the concerns of adult female patients with respect to such treatment. Patients and methods We conducted an explorative study using Q methodology among 40 adult female patients with different educational and social backgrounds in Wenzhou, People’s Republic of China. We asked participants to rank a set of 41 statements about seeking orthodontic treatment on an 11-point scale from “agree most” to “disagree most”. The collected data were analyzed using the PQ Method 2.35 program. We extracted significant viewpoints using centroid factor extraction and varimax rotation. Results We identified major factors based on how the patients ranked statements. Patients in group 1 worried about lack of information about orthodontic treatment, and may have suffered from dental phobia; patients in group 2 were all single women, and they were worried that the braces might lower their chances of finding a partner; patients in group 3 worried about appearance and speech with braces; and patients in group 4 worried about cost, pain, and dental hygiene. The remaining participants who had other viewpoints did not load to any of these four groups. Conclusion The concerns of adult female individuals seeking orthodontic treatment are complex. A significant feature of this study was using Q methodology to analyze the psychological characteristics of the patients. This study identified four typical characterizations that are associated with each group, and our findings may aid orthodontists in improving doctor–patient relationships. PMID:25609926

  16. Use of Q methodology to assess the concerns of adult female individuals seeking orthodontic treatment.

    PubMed

    Yao, Linjie; Xu, Xingqiao; Ni, Zhenyu; Zheng, Minling; Lin, Feiou

    2015-01-01

    Orthodontic treatment may cause functional restrictions, discomfort, and pain, which may lead to dental anxiety and noncooperation among patients. This study aimed to assess the concerns of adult female patients with respect to such treatment. We conducted an explorative study using Q methodology among 40 adult female patients with different educational and social backgrounds in Wenzhou, People's Republic of China. We asked participants to rank a set of 41 statements about seeking orthodontic treatment on an 11-point scale from "agree most" to "disagree most". The collected data were analyzed using the PQ Method 2.35 program. We extracted significant viewpoints using centroid factor extraction and varimax rotation. We identified major factors based on how the patients ranked statements. Patients in group 1 worried about lack of information about orthodontic treatment, and may have suffered from dental phobia; patients in group 2 were all single women, and they were worried that the braces might lower their chances of finding a partner; patients in group 3 worried about appearance and speech with braces; and patients in group 4 worried about cost, pain, and dental hygiene. The remaining participants who had other viewpoints did not load to any of these four groups. The concerns of adult female individuals seeking orthodontic treatment are complex. A significant feature of this study was using Q methodology to analyze the psychological characteristics of the patients. This study identified four typical characterizations that are associated with each group, and our findings may aid orthodontists in improving doctor-patient relationships.

  17. Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott

    Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques.more » These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.« less

  18. Cryopreservation of Cynomolgus Macaque (Macaca fascicularis) Sperm by Using a Commercial Egg-YolkFree Freezing Medium.

    PubMed

    Yan, Yaping; Ao, Lei; Wang, Hong; Duan, Yanchao; Chang, Shaohui; Chen, Bingbing; Zhi, Dalong; Li, Sujuan; Niu, Yuyu; Ji, Weizhi; Si, Wei

    2016-11-01

    Conventional TRISegg yolk (TEY) freezing medium for the cryopreservation of NHP sperm has the risk of contamination due to widespread zoonotic diseases. This study was aimed at determining the optimal glycerol concentration, freezing rate, and holding time in liquid N2 vapor for the cryopreservation of cynomolgus macaque sperm by using a commercial egg-yolkfree freezing medium (SC medium) designed for human sperm cryopreservation. Sperm motility and acrosomal integrity after freezing were assessed. Sperm in SC medium (dilution ratio, 3:1) frozen at cooling rates of 67 and 183C/min in liquid N2 vapor showed higher post-thaw motility than did samples frozen at 435C/min. At the cooling rate of 183C/min and dilution in SC medium at a 3:1 ratio, post-thaw motility was higher after a holding time of 10 min than after 30 min (recommended by the manufacturer). In addition, post-thaw motility of sperm frozen in SC medium was higher with dilution ratios of 3:1, 4.5:1, and 6:1 compared with 9:1, 10.5:1, and 12:1, and the sample diluted 12:1 showed the lowest percentage of thawed sperm with intact acrosomes. Sperm showed higher post-thaw motility after freezing in TEY than in SC medium; acrosomal integrity did not differ between the 2 media. Our results indicated that cynomolgus macaque sperm can be cryopreserved successfully by using a commercial egg-yolkfree freezing medium, which provides an option for genetic preservation with decreased zoonotic risk in this important NHP species.

  19. Post-parturition habitat selection by elk calves and adult female elk in New Mexico

    USGS Publications Warehouse

    Pitman, James W.; Cain, James W.; Liley, Stewart; Gould, William R.; Quintana, Nichole T.; Ballard, Warren

    2014-01-01

    Neonatal survival and juvenile recruitment are crucial to maintaining viable elk (Cervus elaphus) populations. Neonate survival is known to be influenced by many factors, including bed-site selection. Although neonates select the actual bed-site location, they must do so within the larger calf-rearing area selected by the mother. As calves age, habitat selection should change to meet the changing needs of the growing calf. Our main objectives were to characterize habitat selection at 2 spatial scales and in areas with different predator assemblages in New Mexico. We evaluated bed-site selection by calves and calf-rearing area selection by adult females. We captured 108 elk calves by hand and fitted them with ear tag transmitters in two areas in New Mexico: the Valle Vidal and Blue Range Wolf Recovery Area. In both study areas, we found that concealing cover structure and distance to that cover influenced bed-site selection of young calves (i.e., <2 weeks of age). Older calves (i.e., 3–10 weeks of age) still selected areas in relation to distance to cover, but also preferred areas with higher visibility. At the larger spatial scale of calf-rearing habitat selection by the adult female, concealing cover (e.g., rocks, shrubs, and logs) and other variables important to the hiding calves were still in the most supported models, but selection was also influenced by forage availability and indices of forage quality. Studies that seek to obtain insight into microhabitat selection of ungulate neonates should consider selection by the neonate and selection by the adult female, changes in selection as neonates age, and potential selection differences in areas of differing predation risk. By considering these influences together and at multiple scales, studies can achieve a broader understanding of neonatal ungulate habitat requirements. 

  20. Validity of self-reported fertility-threatening cancer treatments in female young adult cancer survivors.

    PubMed

    Roberts, Samantha C; Knight, Amber; Whitcomb, Brian W; Gorman, Jessica R; Dietz, Andrew C; Irene Su, H

    2017-08-01

    Detailed cancer treatment information is important to fertility and pregnancy care of female young adult cancer survivors. Accuracy of self-report of treatments that impact fertility and pregnancy is unknown. This study assessed agreement between self-report and medical records on receipt of fertility-threatening treatments. A national cohort study of female young adult cancer survivors reported cancer treatments via Web-based questionnaires. Primary cancer treatment records were abstracted. Self-reported exposure to fertility-threatening therapies (alkylating chemotherapy, stem cell transplant, pelvic radiation, hysterectomy, and/or oophorectomy) was compared to medical records. Logistic regression models estimated odds ratios (OR) for characteristics associated with inaccurate self-report of fertility-threatening therapies. The study included 101 survivors (mean age 28.2, SD 6.3). Lymphoma (33%), breast cancer (26%), and gynecologic cancers (10%) were the most common cancers. Accuracy of self-report was 68% for alkylating chemotherapy and 92-97% for radiation, surgery, and transplant. Significant proportions of survivors who were treated with transplant (8/13, 62%), alkylating chemotherapy (18/43, 42%), pelvic radiation (4/13, 31%), or hysterectomy and/or oophorectomy (3/13, 23%) did not report undergoing these therapies. In adjusted analysis, age ≤ 25 at diagnosis (OR 3.4, 95% CI 1.3-8.7) and recurrence (OR 6.0, 95% CI 1.5-24.4) were related to inaccurate self-report. Female young adult cancer survivors have limited recall of fertility-threatening cancer treatment exposures. Reproductive health providers and researchers who need this information may require primary medical records or treatment summaries. Additional patient education regarding treatment-related reproductive risks is needed to facilitate patient engagement in survivorship. Obtaining a cancer treatment summary will help survivors communicate their prior treatment exposures to reproductive

  1. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: I. Development of the anatomy

    NASA Astrophysics Data System (ADS)

    Cassola, V. F.; de Melo Lima, V. J.; Kramer, R.; Khoury, H. J.

    2010-01-01

    Among computational models, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images of patients, volunteers or cadavers have become popular in recent years. Although being true to nature representations of scanned individuals, voxel phantoms have limitations, especially when walled organs have to be segmented or when volumes of organs or body tissues, like adipose, have to be changed. Additionally, the scanning of patients or volunteers is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the regular anatomy of a person in the upright position, which in turn can influence organ and tissue absorbed or equivalent dose estimates. This study applies tools developed recently in the areas of computer graphics and animated films to the creation and modelling of 3D human organs, tissues, skeletons and bodies based on polygon mesh surfaces. Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been designed using software, such as MakeHuman, Blender, Binvox and ImageJ, based on anatomical atlases, observing at the same time organ masses recommended by the International Commission on Radiological Protection for the male and female reference adult in report no 89. 113 organs, bones and tissues have been modelled in the FASH and the MASH phantoms representing locations for adults in standing posture. Most organ and tissue masses of the voxelized versions agree with corresponding data from ICRP89 within a margin of 2.6%. Comparison with the mesh-based male RPI_AM and female RPI_AF phantoms shows differences with respect to the material used, to the software and concepts applied, and to the anatomies created.

  2. Serotonin Transporter Gene Polymorphisms and Early Parent-Infant Interactions Are Related to Adult Male Heart Rate Response to Female Crying

    PubMed Central

    Truzzi, Anna; Bornstein, Marc H.; Senese, Vincenzo P.; Shinohara, Kazuyuki; Setoh, Peipei; Esposito, Gianluca

    2017-01-01

    Adults' adaptive interactions with intimate partners enhance well-being. Here we hypothesized that adult males' physiological responses to opposite-sex conspecifics' distress result from an interaction between an environmental factor (early social interaction with caregivers) and a genetic factor (a polymorphism within the promoter region of the serotonin transporter gene, 5-HTTLPR). We assessed heart rate changes in 42 non-married male adults to distress vocalizations (female, infant, and bonobo cries). Males' early interaction with parents was assessed using the Parental Bonding Instrument. Buccal mucosa cell samples were collected to assess their 5-HTTLPR genotype. A significant interaction emerged between early experience and genetic predisposition. Males with a genetic predisposition for higher sensitivity to environmental factors showed atypical physiological responses to adult female cries according to their experienced early maternal parenting. Environmental experiences and genetic characteristics are associated with adult males' physiological responses to socially meaningfully stimuli. Understanding the mechanisms that modulate responses to opposite-sex conspecifics may improve personal well-being and social adaptiveness. PMID:28293197

  3. Gene expression profiling of adult female tissues in feeding Rhipicephalus microplus cattle ticks.

    PubMed

    Stutzer, Christian; van Zyl, Willem A; Olivier, Nicholas A; Richards, Sabine; Maritz-Olivier, Christine

    2013-06-01

    The southern cattle tick, Rhipicephalus microplus, is an economically important pest, especially for resource-poor countries, both as a highly adaptive invasive species and prominent vector of disease. The increasing prevalence of resistance to chemical acaricides and variable efficacy of current tick vaccine candidates highlight the need for more effective control methods. In the absence of a fully annotated genome, the wealth of available expressed sequence tag sequence data for this species presents a unique opportunity to study the genes that are expressed in tissues involved in blood meal acquisition, digestion and reproduction during feeding. Utilising a custom oligonucleotide microarray designed from available singletons (BmiGI Version 2.1) and expressed sequence tag sequences of R. microplus, the expression profiles in feeding adult female midgut, salivary glands and ovarian tissues were compared. From 13,456 assembled transcripts, 588 genes expressed in all three tissues were identified from fed adult females 20 days post infestation. The greatest complement of genes relate to translation and protein turnover. Additionally, a number of unique transcripts were identified for each tissue that relate well to their respective physiological/biological function/role(s). These transcripts include secreted anti-hemostatics and defense proteins from the salivary glands for acquisition of a blood meal, proteases as well as enzymes and transporters for digestion and nutrient acquisition from ingested blood in the midgut, and finally proteins and associated factors involved in DNA replication and cell-cycle control for oogenesis in the ovaries. Comparative analyses of adult female tissues during feeding enabled the identification of a catalogue of transcripts that may be essential for successful feeding and reproduction in the cattle tick, R. microplus. Future studies will increase our understanding of basic tick biology, allowing the identification of shared proteins

  4. Estimation of stature from the foot and its segments in a sub-adult female population of North India.

    PubMed

    Krishan, Kewal; Kanchan, Tanuj; Passi, Neelam

    2011-11-21

    Establishing personal identity is one of the main concerns in forensic investigations. Estimation of stature forms a basic domain of the investigation process in unknown and co-mingled human remains in forensic anthropology case work. The objective of the present study was to set up standards for estimation of stature from the foot and its segments in a sub-adult female population. The sample for the study constituted 149 young females from the Northern part of India. The participants were aged between 13 and 18 years. Besides stature, seven anthropometric measurements that included length of the foot from each toe (T1, T2, T3, T4, and T5 respectively), foot breadth at ball (BBAL) and foot breadth at heel (BHEL) were measured on both feet in each participant using standard methods and techniques. The results indicated that statistically significant differences (p < 0.05) between left and right feet occur in both the foot breadth measurements (BBAL and BHEL). Foot length measurements (T1 to T5 lengths) did not show any statistically significant bilateral asymmetry. The correlation between stature and all the foot measurements was found to be positive and statistically significant (p-value < 0.001). Linear regression models and multiple regression models were derived for estimation of stature from the measurements of the foot. The present study indicates that anthropometric measurements of foot and its segments are valuable in the estimation of stature. Foot length measurements estimate stature with greater accuracy when compared to foot breadth measurements. The present study concluded that foot measurements have a strong relationship with stature in the sub-adult female population of North India. Hence, the stature of an individual can be successfully estimated from the foot and its segments using different regression models derived in the study. The regression models derived in the study may be applied successfully for the estimation of stature in sub-adult

  5. Variables related to tobacco use among young adults: are there differences between males and females?

    PubMed

    Pederson, Linda L; Koval, John J; Chan, Stella S H; Zhang, Xiaohe

    2007-02-01

    We sought to determine the association of four categories (chunks) of variables: (1) demographic characteristics, (2) family and friends smoking and other drug use, (3) psychosocial factors and attitude, and (4) lifestyle factors to current smoking as compared to never smoking among Canadian young adults. A cohort of 1270 young adults, followed for 10 years, completed a self-administered questionnaire. In multivariable analyses, the best final model for both genders did not include the psychosocial and attitudinal categories, but did contain variables in the demographic, family and friends, and lifestyle categories. Interventions for reducing smoking among young adults may be similar for males and females, a conclusion that differs from conclusions based on findings from younger age groups.

  6. Cigarette Smoking is Associated with Body Shape Concerns and Bulimia Symptoms Among Young Adult Females

    PubMed Central

    Kendzor, Darla E.; Adams, Claire E.; Stewart, Diana W.; Baillie, Lauren E.; Copeland, and Amy L.

    2014-01-01

    Elevated rates of cigarette smoking have been reported among individuals with Bulimia Nervosa. However, little is known about eating disorder symptoms within non-clinical samples of smokers. The purpose of the present study was to compare the eating disorder symptoms of young adult female smokers (n = 184) and non-smokers (n = 56), to determine whether smokers were more likely to endorse bulimic symptoms and report greater body shape concern than non-smokers. Analyses indicated that smokers scored significantly higher than non-smokers on the Body Shape Questionnaire, p = .03, and the Bulimia Test-Revised, p = .006. In addition, a higher proportion of smokers than non-smokers scored ≥ 85 on the Bulimia Test-Revised, p = .05, suggesting the possibility that Bulimia Nervosa diagnoses were more prevalent among smokers. No differences were found between smokers and non-smokers on other measures of eating behavior. Overall, findings suggest that smoking is specifically associated with symptoms of Bulimia Nervosa and body shape concern among young adult females. PMID:19171320

  7. Cigarette smoking is associated with body shape concerns and bulimia symptoms among young adult females.

    PubMed

    Kendzor, Darla E; Adams, Claire E; Stewart, Diana W; Baillie, Lauren E; Copeland, Amy L

    2009-01-01

    Elevated rates of cigarette smoking have been reported among individuals with Bulimia Nervosa. However, little is known about eating disorder symptoms within non-clinical samples of smokers. The purpose of the present study was to compare the eating disorder symptoms of young adult female smokers (n=184) and non-smokers (n=56), to determine whether smokers were more likely to endorse bulimic symptoms and report greater body shape concern than non-smokers. Analyses indicated that smokers scored significantly higher than non-smokers on the Body Shape Questionnaire, p=.03, and the Bulimia Test-Revised, p=.006. In addition, a higher proportion of smokers than non-smokers scored > or = 85 on the Bulimia Test-Revised, p=.05, suggesting the possibility that Bulimia Nervosa diagnoses were more prevalent among smokers. No differences were found between smokers and non-smokers on other measures of eating behavior. Overall, findings suggest that smoking is specifically associated with symptoms of Bulimia Nervosa and body shape concern among young adult females.

  8. Dysmenorrhea: Prevalence and Impact on Quality of Life among Young Adult Jordanian Females.

    PubMed

    Al-Jefout, Moamar; Seham, Abu-Fraijeh; Jameel, Hijazeen; Randa, Al-Qaisi; Ola, Al-Ma'aitah; Oday, Al-Ma'aitah; Luscombe, Georgina

    2015-06-01

    To establish the prevalence and impact on quality of life of dysmenorrhea among young adult Jordanian females. Cross-sectional study based on quantitative self-reported anonymous questionnaire. University-based study. A total of 272 female medical students (aged 19-25 years). None. Self-reports of menstruation-related pain symptoms and methods of dealing with them. Of study subjects 152/272 (55.8%) participants had moderate and severe dysmenorrhea. Of them, 55.8% had a family history of severe dysmenorrhea compared with 33.1% of those without dysmenorrhea (χ2 = 13.40, df = 1, P < .001). There was strong association between severity of dysmenorrhea and poor university attendance (χ(2) = 45.35, df = 2, P < .001), poor social activities (χ2 = 32.06, df = 2, P < .001), poor relationships with family (χ2 = 18.46, df = 2, P < .001) and friends (χ2 = 19.14, df = 2, P < .001), and poor sport activities (χ2 = 12.15, df = 2, P = .002). Dysmenorrhea worsens during examination periods in 50% of cases. The most common pain symptom was low back pain (60.2%). Body mass index, family monthly income and early age at menarche had no correlation with the occurrence of dysmenorrhea. Of those with dysmenorrhea, 69.4% were using analgesics. Mothers were the main source of information regarding menstruation. Dysmenorrhea is highly prevalent among young adult Jordanian females and seems to negatively affect quality of life, particularly as related to university attendance and performance and social relationships. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  9. Development of rat female genital cortex and control of female puberty by sexual touch

    PubMed Central

    Lenschow, Constanze; Sigl-Glöckner, Johanna

    2017-01-01

    Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch. PMID:28934203

  10. Development of rat female genital cortex and control of female puberty by sexual touch.

    PubMed

    Lenschow, Constanze; Sigl-Glöckner, Johanna; Brecht, Michael

    2017-09-01

    Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

  11. Identification of a novel simian parvovirus in cynomolgus monkeys with severe anemia. A paradigm of human B19 parvovirus infection.

    PubMed Central

    O'Sullivan, M G; Anderson, D C; Fikes, J D; Bain, F T; Carlson, C S; Green, S W; Young, N S; Brown, K E

    1994-01-01

    Although human B19 parvovirus infection has been clearly associated with a number of distinct syndromes (including severe anemia, abortion, and arthritis), detailed knowledge of its pathogenesis has been hindered by the lack of a suitable animal model. We have identified a novel simian parvovirus in cynomolgus monkeys with severe anemia. Sequencing of a 723-bp fragment of cloned viral DNA extracted from serum revealed that the simian parvovirus has 65% homology at the DNA level with the human B19 parvovirus but little homology with other known parvoviruses. Light microscopic examination of bone marrow from infected animals showed intranuclear inclusion bodies, and ultrastructural studies showed viral arrays characteristic of parvoviruses. Another striking feature was the presence of marked dyserythropoiesis in cells of the erythroid lineage, raising the possibility that B19 parvovirus infection may underlie related dyserythropoietic syndromes in human beings. Affected animals had concurrent infection with the immunosuppressive type D simian retrovirus, analogous to HIV patients who develop severe anemia because of infection with B19 parvovirus. The remarkable similarities between the simian and B19 parvoviruses suggest that experimentally infected cynomolgus monkeys may serve as a useful animal model of human B19 infection. Images PMID:8163659

  12. Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice.

    PubMed

    Pocar, Paola; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano

    2017-05-01

    Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation.

    PubMed

    Ponce, R; Armstrong, K; Andrews, K; Hensler, J; Waggie, K; Heffernan, J; Reynolds, T; Rogge, M

    2005-01-01

    Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

  14. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

    PubMed

    Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

    2013-07-19

    HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  15. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

    PubMed Central

    Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Le Grand, Roger; Fomsgaard, Anders

    2013-01-01

    HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. PMID:26344115

  16. Filarial abscess: Aspiration of adult gravid female worm from submandibular region, an unusual presentation.

    PubMed

    Afrose, Ruquiya; Alam, Mohammad Feroz; Ahmad, Syed Shamshad; Naim, Mohammed

    2017-01-01

    Microfilaria is a major public health problem in tropical and subtropical countries and is an endemic problem in India. Wuchereria bancrofti is the most common filarial infection. In some cases, microfilariae and adult filarial worm have been incidentally detected in fine-needle aspirates of various lesions; detection of microfilaria from subcutaneous site or from abscess site is even rarer. We here report an unusual case of Bancroftian microfilariasis in a 68-year-old female coming from endemic area presenting with right submandibular abscess. Our aim is to highlight the chances of finding microfilaria and adult worm in cytology of an unsuspected case at an unusual site.

  17. Filarial abscess: Aspiration of adult gravid female worm from submandibular region, an unusual presentation

    PubMed Central

    Afrose, Ruquiya; Alam, Mohammad Feroz; Ahmad, Syed Shamshad; Naim, Mohammed

    2017-01-01

    Microfilaria is a major public health problem in tropical and subtropical countries and is an endemic problem in India. Wuchereria bancrofti is the most common filarial infection. In some cases, microfilariae and adult filarial worm have been incidentally detected in fine-needle aspirates of various lesions; detection of microfilaria from subcutaneous site or from abscess site is even rarer. We here report an unusual case of Bancroftian microfilariasis in a 68-year-old female coming from endemic area presenting with right submandibular abscess. Our aim is to highlight the chances of finding microfilaria and adult worm in cytology of an unsuspected case at an unusual site. PMID:28182103

  18. Factors affecting survival of adult female white-tailed deer after coyote establishment in South Carolina

    Treesearch

    John C. Kilgo; Mark Vukovich; Michael J. Conroy; H. Scott Ray; Charles Ruth

    2016-01-01

    Recent evidence from the southeastern United States of high predation rates by coyotes (Canis latrans) on white-tailed deer (Odocoileus virginianus) fawns combined with reports of predation on adult female deer have prompted concern among wildlifemanagers and hunters regarding the effects ondeer populations.We examined survival rates and causes of...

  19. Coping with incest: the relationship between recollections of childhood coping and adult functioning in female survivors of incest.

    PubMed

    Brand, Bethany L; Alexander, Pamela C

    2003-06-01

    One hundred and one adult female survivors' recollections of coping with childhood incest, abuse characteristics, and current functioning in adulthood were studied. Analyses controlling for characteristics of the trauma indicated that recollections of using avoidance coping and seeking social support were related to poor adult functioning whereas recollections of using distancing coping were related to better functioning. As a set of variables, abuse characteristics also predicted a significant amount of variance in adult functioning. Implications for future research were discussed.

  20. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

    PubMed

    Lumbroso, Delphine; Joseph, Vincent

    2009-08-01

    We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.

  1. Cowpox virus infection of cynomolgus macaques as a model of hemorrhagic smallpox.

    PubMed

    Johnson, Reed F; Yellayi, Srikanth; Cann, Jennifer A; Johnson, Anthony; Smith, Alvin L; Paragas, Jason; Jahrling, Peter B; Blaney, Joseph E

    2011-09-30

    Hemorrhagic smallpox was a rare but severe manifestation of variola virus infection that resulted in nearly 100% mortality. Here we describe intravenous (IV) inoculation of cowpox virus Brighton Red strain in cynomolgus macaques (Macaca fascicularis) which resulted in disease similar in presentation to hemorrhagic smallpox in humans. IV inoculation of macaques resulted in a uniformly lethal disease within 12 days post-inoculation in two independent experiments. Clinical observations and hematological and histopathological findings support hemorrhagic disease. Cowpox virus replicated to high levels in blood (8.0-9.0 log(10) gene copies/mL) and tissues including lymph nodes, thymus, spleen, bone marrow, and lungs. This unique model of hemorrhagic orthopoxvirus infection provides an accessible means to further study orthopoxvirus pathogenesis and to identify virus-specific and nonspecific therapies. Such studies will serve to complement the existing nonhuman primate models of more classical poxviral disease. Published by Elsevier Inc.

  2. Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

    PubMed Central

    Geisbert, Thomas W.; Hensley, Lisa E.; Larsen, Tom; Young, Howard A.; Reed, Douglas S.; Geisbert, Joan B.; Scott, Dana P.; Kagan, Elliott; Jahrling, Peter B.; Davis, Kelly J.

    2003-01-01

    Ebola virus (EBOV) infection causes a severe and fatal hemorrhagic disease that in many ways appears to be similar in humans and nonhuman primates; however, little is known about the development of EBOV hemorrhagic fever. In the present study, 21 cynomolgus monkeys were experimentally infected with EBOV and examined sequentially over a 6-day period to investigate the pathological events of EBOV infection that lead to death. Importantly, dendritic cells in lymphoid tissues were identified as early and sustained targets of EBOV, implicating their important role in the immunosuppression characteristic of EBOV infections. Bystander lymphocyte apoptosis, previously described in end-stage tissues, occurred early in the disease-course in intravascular and extravascular locations. Of note, apoptosis and loss of NK cells was a prominent finding, suggesting the importance of innate immunity in determining the fate of the host. Analysis of peripheral blood mononuclear cell gene expression showed temporal increases in tumor necrosis factor-related apoptosis-inducing ligand and Fas transcripts, revealing a possible mechanism for the observed bystander apoptosis, while up-regulation of NAIP and cIAP2 mRNA suggest that EBOV has evolved additional mechanisms to resist host defenses by inducing protective transcripts in cells that it infects. The sequence of pathogenetic events identified in this study should provide new targets for rational prophylactic and chemotherapeutic interventions. PMID:14633608

  3. Sexual Abuse Perpetrated by Adult and Juvenile Females: An Ultimate Attempt to Resolve a Conflict Associated with Maternal Identity

    ERIC Educational Resources Information Center

    Tardif, M.; Auclair, N.; Jacob, M.; Carpentier, J.

    2005-01-01

    Objective:: The purpose of this article is to report the descriptive and phenomenological aspects of adult females (AF) and juvenile females (JF) who sexually abuse children and adolescents. A major focus is to study the relational problems during childhood and adulthood of this specific population and how they echo the relational aspects of their…

  4. Alprazolam as an in vivo probe for studying induction of CYP3A in cynomolgus monkeys.

    PubMed

    Ohtsuka, Tatsuyuki; Yoshikawa, Takahiro; Kozakai, Kazumasa; Tsuneto, Yumi; Uno, Yasuhiro; Utoh, Masahiro; Yamazaki, Hiroshi; Kume, Toshiyuki

    2010-10-01

    Induction of the cytochrome P450 (P450) enzyme is a major concern in the drug discovery processes. To predict the clinical significance of enzyme induction, it is helpful to investigate pharmacokinetic alterations of a coadministered drug in a suitable animal model. In this study, we focus on the induction of CYP3A, which is involved in the metabolism of approximately 50% of marketed drugs and is inducible in both the liver and intestine. As a marker substrate for CYP3A activity, alprazolam (APZ) was selected and characterized using recombinant CYP3A enzymes expressed in Escherichia coli. Both human CYP3A4 and its cynomolgus P450 ortholog predominantly catalyzed APZ 4-hydroxylation with sigmoidal kinetics. When administered intravenously and orally to cynomolgus monkeys, APZ had moderate clearance; its first-pass extraction ratio after oral dosing was estimated to be 0.09 in the liver and 0.45 in the intestine. Pretreatment with multiple doses of rifampicin (20 mg/kg p.o. for 5 days), a known CYP3A inducer, significantly decreased plasma concentrations of APZ after intravenous and oral administrations (0.5 mg/kg), and first-pass extraction ratios were increased to 0.39 in the liver and 0.63 in the intestine. The results were comparable to those obtained in clinical drug-drug interaction (DDI) reports related to CYP3A induction, although the rate of recovery of CYP3A activity seemed to be slower than rates estimated in clinical studies. In conclusion, pharmacokinetic studies using APZ as a probe in monkeys may provide useful information regarding the prediction of clinical DDIs due to CYP3A induction.

  5. Cryopreservation of Cynomolgus Macaque (Macaca fascicularis) Sperm by Using a Commercial Egg-Yolk–Free Freezing Medium

    PubMed Central

    Yan, Yaping; Ao, Lei; Wang, Hong; Duan, Yanchao; Chang, Shaohui; Chen, Bingbing; Zhi, Dalong; Li, Sujuan; Niu, Yuyu; Ji, Weizhi; Si, Wei

    2016-01-01

    Conventional TRIS–egg yolk (TEY) freezing medium for the cryopreservation of NHP sperm has the risk of contamination due to widespread zoonotic diseases. This study was aimed at determining the optimal glycerol concentration, freezing rate, and holding time in liquid N2 vapor for the cryopreservation of cynomolgus macaque sperm by using a commercial egg-yolk–free freezing medium (SC medium) designed for human sperm cryopreservation. Sperm motility and acrosomal integrity after freezing were assessed. Sperm in SC medium (dilution ratio, 3:1) frozen at cooling rates of –67° and –183°C/min in liquid N2 vapor showed higher post-thaw motility than did samples frozen at –435 °C/min. At the cooling rate of –183 °C/min and dilution in SC medium at a 3:1 ratio, post-thaw motility was higher after a holding time of 10 min than after 30 min (recommended by the manufacturer). In addition, post-thaw motility of sperm frozen in SC medium was higher with dilution ratios of 3:1, 4.5:1, and 6:1 compared with 9:1, 10.5:1, and 12:1, and the sample diluted 12:1 showed the lowest percentage of thawed sperm with intact acrosomes. Sperm showed higher post-thaw motility after freezing in TEY than in SC medium; acrosomal integrity did not differ between the 2 media. Our results indicated that cynomolgus macaque sperm can be cryopreserved successfully by using a commercial egg-yolk–free freezing medium, which provides an option for genetic preservation with decreased zoonotic risk in this important NHP species. PMID:27931311

  6. Adolescent Female Cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ9-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring.

    PubMed

    Pitsilis, George; Spyridakos, Dimitrios; Nomikos, George G; Panagis, George

    2017-01-01

    Marijuana is currently the most commonly abused illicit drug. According to recent studies, cannabinoid use occurring prior to pregnancy can impact brain plasticity and behavior in future generations. The purpose of the present study was to determine whether adolescent exposure of female rats to Δ 9 -tetrahydrocannabinol (Δ 9 -THC) induces transgenerational effects on the reward-facilitating effects of Δ 9 -THC and d -amphetamine in their adult male offspring. Female Sprague-Dawley rats received Δ 9 -THC (0.1 or 1 mg/kg, i.p.) or vehicle during postnatal days 28-50. As adults, females were mated with drug-naïve males. We then assessed potential alterations of the Δ 9 -THC's (0, 0.1, 0.5, and 1 mg/kg, i.p.) and d -amphetamine's (0, 0.1, 0.5, and 1 mg/kg, i.p.) reward-modifying effects using the curve-shift variant of the intracranial self-stimulation (ICSS) procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ 9 -THC was abolished in the F1 offspring of females that were exposed to Δ 9 -THC (0.1 or 1 mg/kg), whereas the reward-attenuating effect of the 1 mg dose of Δ 9 -THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d -amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ 9 -THC (1 mg/kg and 0.1 or 1 mg, respectively). The present results reveal that female Δ 9 -THC exposure during adolescence can diminish the reward-facilitating effects of Δ 9 -THC and d -amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure. It is speculated that Δ 9 -THC exposure during female adolescence may affect neural mechanisms that are shaping reward-related behavioral responses in a subsequent generation, as indicated by the shifts in the reward-facilitating effects of commonly used and abused drugs.

  7. Effect of road transportation on the serum biochemical parameters of cynomolgus monkeys and beagle dogs.

    PubMed

    Ochi, Takehiro; Yamada, Azusa; Naganuma, Yuki; Nishina, Noriko; Koyama, Hironari

    2016-06-01

    To determine the effect of long-distance (approximately 600 km) road transportation on the blood biochemistry of laboratory animals, we investigated the changes in serum biochemical parameters in healthy cynomolgus monkeys and beagle dogs transported by truck from Osaka to Tsukuba, Japan. The concentrations of serum cortisol, total bilirubin and aspartate aminotransferase in monkeys increased during transportation. Serum cortisol and total bilirubin levels in dogs also increased during transportation, but serum triglyceride decreased. Serum parameter values in truck-transported monkeys and dogs returned to baseline levels within two weeks following arrival. Taken together, these results suggest that a two-week acclimation period is the minimum duration required for adaptation following road transportation.

  8. Immunogenicity of recombinant measles vaccine expressing fusion protein of respiratory syncytial virus in cynomolgus monkeys.

    PubMed

    Sawada, Akihito; Yunomae, Kiyokazu; Nakayama, Tetsuo

    2018-02-01

    Respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants. Effective vaccines are currently being sought, but no vaccine is thus far available. In our previous study, recombinant AIK-C measles vaccine expressing the RSV fusion protein (MVAIK/RSV/F) was developed and protective immunity against RSV demonstrated in cotton rats. In the present study, the immunogenicity and protective effects were investigated in three cynomolgus monkeys immunized with MVAIK/RSV/F. Neutralizing test antibodies against RSV were detected and no infectious virus was recovered from the lungs of monkeys immunized with MVAIK/RSV/F after challenge. MVAIK/RSV/F has the potential to inhibit RSV infection. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

  9. Ladies first: Female and male adult height in Switzerland, 1770-1930.

    PubMed

    Koepke, Nikola; Floris, Joël; Pfister, Christian; Rühli, Frank J; Staub, Kaspar

    2018-05-01

    When investigating the well-being of a society, the living conditions of females are of special importance, not only due to the immediate impact for those directly involved, but also because of the potential intergenerational effects. Studying the dimorphism in the mean height helps to depict variation in the basic biological sex difference due to gender-related factors that potentially determine net nutrition. To expand knowledge of diachronic development in Swiss well-being conditions we investigate changes in the height of adult females born 1770-1930, and compare the series with data on contemporary males from the same sources: We employ a sample of N = 21'028 women and N = 21'329 men from passport-, convict-, maternity hospital-, and voluntary World War II army auxiliary records. The secular height trend is found both in males, from the 1870s/1880s, and in females starting with the 1840s/1850s birth cohorts. During the decades under study, mean height increased from 157 cm to 164 cm in female and 167 cm to 172 cm in male passport applicants, 154 cm to 159 cm in female and 167 cm to 169 cm in male convicts, 159 cm to 163 cm in female auxiliaries, and 155 cm to 159 cm in females giving birth in the maternity hospital of Basel. Because females seem to have started the secular trend in height earlier than their male contemporaries, the height dimorphism decreased during the second half of the 19th century. Differences between socio-economic status (SES) and data sources are found in both females and males: Women with low SES were significantly shorter than those of the other SES groups in all sources (on average 1.40 cm, p-values between 0.00 and 0.03). In men we found individuals of upper SES to be significantly taller (on average 1.96 cm, p-value = 0.00-0.10). Concerning differences between the sources, overall, passport applicants were the tallest for men as well as women; in females the individuals measured at the

  10. Estimating total population size for adult female sea turtles: Accounting for non-nesters

    USGS Publications Warehouse

    Kendall, W.L.; Richardson, J.I.; Rees, Alan F.

    2008-01-01

    Assessment of population size and changes therein is important to sea turtle management and population or life history research. Investigators might be interested in testing hypotheses about the effect of current population size or density (number of animals per unit resource) on future population processes. Decision makers might want to determine a level of allowable take of individual turtles of specified life stage. Nevertheless, monitoring most stages of sea turtle life histories is difficult, because obtaining access to individuals is difficult. Although in-water assessments are becoming more common, nesting females and their hatchlings remain the most accessible life stages. In some cases adult females of a given nesting population are sufficiently philopatric that the population itself can be well defined. If a well designed tagging study is conducted on this population, survival, breeding probability, and the size of the nesting population in a given year can be estimated. However, with published statistical methodology the size of the entire breeding population (including those females skipping nesting in that year) cannot be estimated without assuming that each adult female in this population has the same probability of nesting in a given year (even those that had just nested in the previous year). We present a method for estimating the total size of a breeding population (including nesters those skipping nesting) from a tagging study limited to the nesting population, allowing for the probability of nesting in a given year to depend on an individual's nesting status in the previous year (i.e., a Markov process). From this we further develop estimators for rate of growth from year to year in both nesting population and total breeding population, and the proportion of the breeding population that is breeding in a given year. We also discuss assumptions and apply these methods to a breeding population of hawksbill sea turtles (Eretmochelys imbricata) from

  11. New Insights into the Comorbidity between ADHD and Major Depression in Adolescent and Young Adult Females

    ERIC Educational Resources Information Center

    Biederman, Joseph; Ball, Sarah W.; Monuteaux, Michael C.; Mick, Eric; Spencer, Thomas J.; McCreary, Michelle; Cote, Michelle; Faraone, Stephen V.

    2008-01-01

    The association between attention-deficit/hyperactivity disorder (ADHD) and major depression (MD) in adolescent and young adult females is evaluated. Findings indicate that MD emerging in the context of ADHD is an impairing and severe comorbidity that needs to be considered further clinically and scientifically.

  12. Cynomolgus macaques naturally infected with Trypanosoma cruzi-I exhibit an overall mixed pro-inflammatory/modulated cytokine signature characteristic of human Chagas disease.

    PubMed

    Vitelli-Avelar, Danielle Marquete; Sathler-Avelar, Renato; Mattoso-Barbosa, Armanda Moreira; Gouin, Nicolas; Perdigão-de-Oliveira, Marcelo; Valério-Dos-Reis, Leydiane; Costa, Ronaldo Peres; Elói-Santos, Silvana Maria; Gomes, Matheus de Souza; Amaral, Laurence Rodrigues do; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Dick, Edward J; Hubbard, Gene B; VandeBerg, Jane F; VandeBerg, John L

    2017-02-01

    Non-human primates have been shown to be useful models for Chagas disease. We previously reported that natural T. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human Chagas disease. In the present study, we further characterize the cytokine-mediated microenvironment to provide supportive evidence of the utility of cynomolgus macaques as a model for drug development for human Chagas disease. In this cross-sectional study design, flow cytometry and systems biology approaches were used to characterize the ex vivo and in vitro T. cruzi-specific functional cytokine signature of circulating leukocytes from TcI-T. cruzi naturally infected cynomolgus macaques (CH). Results showed that CH presented an overall CD4+-derived IFN-γ pattern regulated by IL-10-derived from CD4+ T-cells and B-cells, contrasting with the baseline profile observed in non-infected hosts (NI). Homologous TcI-T. cruzi-antigen recall in vitro induced a broad pro-inflammatory cytokine response in CH, mediated by TNF from innate/adaptive cells, counterbalanced by monocyte/B-cell-derived IL-10. TcIV-antigen triggered a more selective cytokine signature mediated by NK and T-cell-derived IFN-γ with modest regulation by IL-10 from T-cells. While NI presented a cytokine network comprised of small number of neighborhood connections, CH displayed a complex cross-talk amongst network elements. Noteworthy, was the ability of TcI-antigen to drive a complex global pro-inflammatory network mediated by TNF and IFN-γ from NK-cells, CD4+ and CD8+ T-cells, regulated by IL-10+CD8+ T-cells, in contrast to the TcIV-antigens that trigger a modest network, with moderate connecting edges. Altogether, our findings demonstrated that CH present a pro-inflammatory/regulatory cytokine signature similar to that observed in human Chagas disease. These data bring additional insights that further validate these non

  13. Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pocar, Paola, E-mail: paola.pocar@unimi.it; Fianda

    Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring.more » In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation.

  14. Embryonic exposure to benzo(a)pyrene inhibits reproductive capability in adult female zebrafish and correlation with DNA methylation.

    PubMed

    Gao, Dongxu; Lin, Jing; Ou, Kunlin; Chen, Ying; Li, Hongbin; Dai, Qinhua; Yu, Zhenni; Zuo, Zhenghong; Wang, Chonggang

    2018-05-09

    This study was conducted to investigate the effects of embryonic short-term exposure to benzo(a)pyrene (BaP), a model polycyclic aromatic hydrocarbon, on ovarian development and reproductive capability in adult female zebrafish. In 1-year-old fish after embryonic exposure to BaP for 96 h, the gonadosomatic indices and the percentage of mature oocytes were significantly decreased in the 0.5, 5 and 50 nmol/L treatments. The spawned egg number, the fertilization rate and the hatching success were significantly reduced, while the malformation rate of the F1 unexposed larvae were increased. The mRNA levels of follicle-stimulating hormone, luteinizing hormone, ovarian cytochrome P450 aromatase cyp19a1a and cyp19b, estrogen receptor esr1 and esr2, and hepatic vitellogenin vtg1 and vtg2 genes, were down-regulated in adult female zebrafish that were exposed to BaP during embryonic stage. Both 17β-estradiol and testosterone levels were reduced in the ovary of adult females. The methylation levels of the gonadotropin releasing hormone (GnRH) gene gnrh3 were significantly increased in the adult zebrafish brain, and those of the GnRH receptor gene gnrhr3 were elevated both in the larvae exposed to BaP and in the adult brain, which might cause the down-regulation of the mRNA levels of gnrh3 and gnrhr3. This epigenetic change caused by embryonic exposure to BaP might be a reason for physiological changes along the brain-pituitary-gonad axis. These results suggest that short-term exposure in early life should be included and evaluated in any risk assessment of pollutant exposure to the reproductive health of fish. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. The sexually dimorphic behaviour of adult Drosophila suzukii: elevated female locomotor activity and loss of siesta is a post-mating response.

    PubMed

    Ferguson, Calum T J; O'Neill, Tara L; Audsley, Neil; Isaac, R Elwyn

    2015-12-01

    The polyphagous Drosophila suzukii is a highly invasive species that causes extensive damage to a wide range of berry and stone fruit crops. A better understanding of its biology and especially its behaviour will aid the development of new control strategies. We investigated the locomotor behaviour of D. suzukii in a semi-natural environment resembling a typical summer in northern England and show that adult female D. suzukii are at least 4-fold more active during daylight hours than adult males. This result was reproduced in several laboratory environments and was shown to be a robust feature of mated, but not virgin, female flies. Both males and virgin females kept on a 12 h light:12 h dark (12LD) cycle and constant temperature displayed night-time inactivity (sleep) followed by weak activity in the morning, an afternoon period of quiescence (siesta) and then a prominent evening peak of activity. Both the siesta and the sharp evening peak at lights off were severely reduced in females after mating. Flies of either sex entrained in 12LD displayed a circadian pattern of activity in constant darkness confirming the importance of an endogenous clock in regulating adult activity. This response of females to mating is similar to that elicited in female Drosophila melanogaster by the male sex peptide (SP). We used mass spectrometry to identify a molecular ion (m/z, 5145) corresponding to the poly-hydroxylated SP of D. suzukii and to show that this molecule is transferred to the female reproductive tract during copulation. We propose that the siesta experienced by male and virgin female D. suzukii is an adaptation to avoid unnecessary exposure to the afternoon sun, but that mated females faced with the challenge of obtaining resources for egg production and finding oviposition sites take greater risks, and we suggest that the change in female behaviour is induced by the male SP. © 2015. Published by The Company of Biologists Ltd.

  16. Network Analysis of Intrinsic Functional Brain Connectivity in Male and Female Adult Smokers: A Preliminary Study.

    PubMed

    Moran-Santa Maria, Megan M; Vanderweyen, Davy C; Camp, Christopher C; Zhu, Xun; McKee, Sherry A; Cosgrove, Kelly P; Hartwell, Karen J; Brady, Kathleen T; Joseph, Jane E

    2018-06-07

    The goal of this study was to conduct a preliminary network analysis (using graph-theory measures) of intrinsic functional connectivity in adult smokers, with an exploration of sex differences in smokers. Twenty-seven adult smokers (13 males; mean age = 35) and 17 sex and age-matched controls (11 males; mean age = 35) completed a blood oxygen level-dependent resting state functional magnetic resonance imaging experiment. Data analysis involved preprocessing, creation of connectivity matrices using partial correlation, and computation of graph-theory measures using the Brain Connectivity Toolbox. Connector hubs and additional graph-theory measures were examined for differences between smokers and controls and correlations with nicotine dependence. Sex differences were examined in a priori regions of interest based on prior literature. Compared to nonsmokers, connector hubs in smokers emerged primarily in limbic (parahippocampus) and salience network (cingulate cortex) regions. In addition, global influence of the right insula and left nucleus accumbens was associated with higher nicotine dependence. These trends were present in male but not female smokers. Network communication was altered in smokers, primarily in limbic and salience network regions. Network topology was associated with nicotine dependence in male but not female smokers in regions associated with reinforcement (nucleus accumbens) and craving (insula), consistent with the idea that male smokers are more sensitive to the reinforcing aspects of nicotine than female smokers. Identifying alterations in brain network communication in male and female smokers can help tailor future behavioral and pharmacological smoking interventions. Male smokers showed alterations in brain networks associated with the reinforcing effects of nicotine more so than females, suggesting that pharmacotherapies targeting reinforcement and craving may be more efficacious in male smokers.

  17. Estimation of stature from the foot and its segments in a sub-adult female population of North India

    PubMed Central

    2011-01-01

    Background Establishing personal identity is one of the main concerns in forensic investigations. Estimation of stature forms a basic domain of the investigation process in unknown and co-mingled human remains in forensic anthropology case work. The objective of the present study was to set up standards for estimation of stature from the foot and its segments in a sub-adult female population. Methods The sample for the study constituted 149 young females from the Northern part of India. The participants were aged between 13 and 18 years. Besides stature, seven anthropometric measurements that included length of the foot from each toe (T1, T2, T3, T4, and T5 respectively), foot breadth at ball (BBAL) and foot breadth at heel (BHEL) were measured on both feet in each participant using standard methods and techniques. Results The results indicated that statistically significant differences (p < 0.05) between left and right feet occur in both the foot breadth measurements (BBAL and BHEL). Foot length measurements (T1 to T5 lengths) did not show any statistically significant bilateral asymmetry. The correlation between stature and all the foot measurements was found to be positive and statistically significant (p-value < 0.001). Linear regression models and multiple regression models were derived for estimation of stature from the measurements of the foot. The present study indicates that anthropometric measurements of foot and its segments are valuable in the estimation of stature. Foot length measurements estimate stature with greater accuracy when compared to foot breadth measurements. Conclusions The present study concluded that foot measurements have a strong relationship with stature in the sub-adult female population of North India. Hence, the stature of an individual can be successfully estimated from the foot and its segments using different regression models derived in the study. The regression models derived in the study may be applied successfully for the

  18. Using adult Aedes aegypti females to predict areas at risk for dengue transmission: A spatial case-control study.

    PubMed

    Parra, Maisa Carla Pereira; Fávaro, Eliane Aparecida; Dibo, Margareth Regina; Mondini, Adriano; Eiras, Álvaro Eduardo; Kroon, Erna Geessien; Teixeira, Mauro Martins; Nogueira, Mauricio Lacerda; Chiaravalloti-Neto, Francisco

    2018-06-01

    Traditional indices for measuring dengue fever risk in a given area are based on the immature forms of the vector (larvae and pupae surveys). However, this is inefficient because only adult female mosquitoes actually transmit the virus. Based on these assumptions, our objective was to evaluate the association between an entomological index obtained from adult mosquito traps and the occurrence of dengue in a hyperendemic area. Additionally, we compared its cost to that of the Breteau Index (BI). We performed this study in São José do Rio Preto, SP, Brazil, between the epidemiological weeks of 36/2012 and 19/2013. BG-Sentinel and BG-Mosquitito traps were installed to capture adult mosquitoes. Positive and negative cases of dengue fever were computed and geocoded. We generated biweekly thematic maps of the entomological index, generated by calculating the number of adult Aedes aegypti females (NAF) per 100 households during a week by kriging, and based on the number of mosquitoes captured. The relation between the occurrence of dengue fever and the NAF was tested using a spatial case-control design and a generalized additive model and was controlled by the coordinates of the positive and negative cases of dengue fever. Our analyses showed that increases in dengue fever cases occurred in parallel with increases in the number of Ae. aegypti females. The entomological index produced in our study correlates positively with the incidence of dengue, particularly during intervals when vector control measures were applied less intensively. The operational costs of our index were lower than those of the BI: NAF used 71.5% less human resources necessary to measure the BI. Spatial analysis techniques and the number of adult Ae. aegypti females were used to produce an indicator of dengue risk. The index can be applied at various levels of spatial aggregation for an entire study area, as well as for sub-areas, such as city blocks. Even though the index is adequate to predict

  19. Organ doses for reference adult male and female undergoing computed tomography estimated by Monte Carlo simulations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Choonsik; Kim, Kwang Pyo; Long, Daniel

    2011-03-15

    Purpose: To develop a computed tomography (CT) organ dose estimation method designed to readily provide organ doses in a reference adult male and female for different scan ranges to investigate the degree to which existing commercial programs can reasonably match organ doses defined in these more anatomically realistic adult hybrid phantomsMethods: The x-ray fan beam in the SOMATOM Sensation 16 multidetector CT scanner was simulated within the Monte Carlo radiation transport code MCNPX2.6. The simulated CT scanner model was validated through comparison with experimentally measured lateral free-in-air dose profiles and computed tomography dose index (CTDI) values. The reference adult malemore » and female hybrid phantoms were coupled with the established CT scanner model following arm removal to simulate clinical head and other body region scans. A set of organ dose matrices were calculated for a series of consecutive axial scans ranging from the top of the head to the bottom of the phantoms with a beam thickness of 10 mm and the tube potentials of 80, 100, and 120 kVp. The organ doses for head, chest, and abdomen/pelvis examinations were calculated based on the organ dose matrices and compared to those obtained from two commercial programs, CT-EXPO and CTDOSIMETRY. Organ dose calculations were repeated for an adult stylized phantom by using the same simulation method used for the adult hybrid phantom. Results: Comparisons of both lateral free-in-air dose profiles and CTDI values through experimental measurement with the Monte Carlo simulations showed good agreement to within 9%. Organ doses for head, chest, and abdomen/pelvis scans reported in the commercial programs exceeded those from the Monte Carlo calculations in both the hybrid and stylized phantoms in this study, sometimes by orders of magnitude. Conclusions: The organ dose estimation method and dose matrices established in this study readily provides organ doses for a reference adult male and female for

  20. Anaerobic cycling performance characteristics in prepubescent, adolescent and young adult females.

    PubMed

    Doré, E; Bedu, M; França, N M; Van Praagh, E

    2001-05-01

    The purpose of this study was to determine whether the relationships between short-term power and body dimensions in young females were similar whatever the age of the individuals. A cohort of 189 prepubescent (mean age 9.5 years), adolescent (mean age 14.4 years) and young adult (mean age 18.2 years) females performed three all-out sprints on a friction-loaded cycle ergometer against three braking forces corresponding to applied loads of 25, 50 and 75 g.kg-1 body mass (BM). For each sprint, peak power including flywheel inertia was calculated. Results showed that a braking load of 75 g.kg-1 BM was too high for prepubescent and adolescent girls. Therefore, when measuring short-term cycling performance in heterogeneous female populations, a braking load of 50 g.kg-1 BM (0.495 N.kg-1 BM) is recommended. During growth, cycling peak power (CPP; defined as the highest peak power obtained during the three sprints) increased, as did total BM, fat-free mass (FFM) and lean leg volume (LLV) (P < 0.001). Analysis of covariance revealed that the slopes of the linear relationships between CPP and biometric characteristics were similar in the three groups (P > 0.7 for the CPP/BM and CPP/FFM relationships, and P > 0.2 for the CPP/LLV relationship). However, the adjusted means were always significantly higher in young women (P < 0.001) compared with both of the other groups. Although differences in performance during anaerobic cycling in growing females are primarily dependent upon body dimensions, other as yet undetermined factors may be involved during late adolescence.

  1. Variation of electrolaryngographically derived closed quotient for trained and untrained adult female singers.

    PubMed

    Howard, D M

    1995-06-01

    The derivation of larynx closed quotient (CQ) measures from the electrolarynogograph output is discussed and data are presented for a group of trained and untrained adult female singers (N = 26) for a sung two-octave G major scale. Statistically significant trends are observed between the trained and untrained groups that suggest for the trained group: (a) CQ tends to be lower for pitches below D4 and higher for pitches above B4, and (b) the gradient [CQ/log(F0)] tends to correlate positively with the number of years singing training/experience. These data are compared with those reported previously for an adult male group, and it is suggested that CQ could be a useful parameter to include in a real-time visual display for singing training.

  2. Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys

    PubMed Central

    Abbott, David H; Tarantal, Alice F; Dumesic, Daniel A

    2010-01-01

    Old World monkeys provide naturally-occurring and experimentally-induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally-induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia, and increased incidence of type 2 diabetes that characterize early gestated-exposed PA adults. These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin-glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood. PMID

  3. Positive Adult Support and Depression Symptoms in Adolescent Females: The Partially Mediating Role of Eating Disturbances

    ERIC Educational Resources Information Center

    Linville, Deanna; O'Neil, Maya; Huebner, Angela

    2011-01-01

    This study examined linkages between depression symptoms (DEP) and positive adult support (PAS) in female adolescents and the partially mediating influence of eating disturbances (ED). Structural equation modeling was used to establish measurement models for each of the latent constructs, determine the relationships among the latent constructs,…

  4. Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

    PubMed Central

    Pawluski, Jodi L.; van Donkelaar, Eva; Abrams, Zipporah; Steinbusch, Harry W. M.; Charlier, Thierry D.

    2014-01-01

    Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat. PMID:24757568

  5. Fenofibrate Metabolism in the Cynomolgus Monkey using Ultraperformance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry-Based MetabolomicsS⃞

    PubMed Central

    Liu, Aiming; Patterson, Andrew D.; Yang, Zongtao; Zhang, Xinying; Liu, Wei; Qiu, Fayang; Sun, He; Krausz, Kristopher W.; Idle, Jeffrey R.; Gonzalez, Frank J.; Dai, Renke

    2009-01-01

    Fenofibrate, widely used for the treatment of dyslipidemia, activates the nuclear receptor, peroxisome proliferator-activated receptor α. However, liver toxicity, including liver cancer, occurs in rodents treated with fibrate drugs. Marked species differences occur in response to fibrate drugs, especially between rodents and humans, the latter of which are resistant to fibrate-induced cancer. Fenofibrate metabolism, which also shows species differences, has not been fully determined in humans and surrogate primates. In the present study, the metabolism of fenofibrate was investigated in cynomolgus monkeys by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS)-based metabolomics. Urine samples were collected before and after oral doses of fenofibrate. The samples were analyzed in both positive-ion and negative-ion modes by UPLC-QTOFMS, and after data deconvolution, the resulting data matrices were subjected to multivariate data analysis. Pattern recognition was performed on the retention time, mass/charge ratio, and other metabolite-related variables. Synthesized or purchased authentic compounds were used for metabolite identification and structure elucidation by liquid chromatographytandem mass spectrometry. Several metabolites were identified, including fenofibric acid, reduced fenofibric acid, fenofibric acid ester glucuronide, reduced fenofibric acid ester glucuronide, and compound X. Another two metabolites (compound B and compound AR), not previously reported in other species, were characterized in cynomolgus monkeys. More importantly, previously unknown metabolites, fenofibric acid taurine conjugate and reduced fenofibric acid taurine conjugate were identified, revealing a previously unrecognized conjugation pathway for fenofibrate. PMID:19251819

  6. Relative influence of human harvest, carnivores, and weather on adult female elk survival across western North America

    USGS Publications Warehouse

    Brodie, Jedediah; Johnson, Heather; Mitchell, Michael; Zager, Peter; Proffitt, Kelly; Hebblewhite, Mark; Kauffman, Matthew; Johnson, Bruce; Bissonette, John; Bishop, Chad; Gude, Justin; Herbert, Jeff; Hersey, Kent R.; Hurley, Mark; Lukacs, Paul M.; McCorquodale, Scott; McIntire, Eliot; Nowak, Josh; Sawyer, Hall; Smith, Douglas; White, P.J.

    2013-01-01

    Well-informed management of harvested species requires understanding how changing ecological conditions affect demography and population dynamics, information that is lacking for many species. We have limited understanding of the relative influence of carnivores, harvest, weather and forage availability on elk Cervus elaphus demography, despite the ecological and economic importance of this species. We assessed adult female survival, a key vital rate for population dynamics, from 2746 radio-collared elk in 45 populations across western North America that experience wide variation in carnivore assemblage, harvest, weather and habitat conditions. Proportional hazard analysis revealed that 'baseline' (i.e. not related to human factors) mortality was higher with very high winter precipitation, particularly in populations sympatric with wolves Canis lupus. Mortality may increase via nutritional stress and heightened vulnerability to predation in snowy winters. Baseline mortality was unrelated to puma Puma concolor presence, forest cover or summer forage productivity. Cause-specific mortality analyses showed that wolves and all carnivore species combined had additive effects on baseline elk mortality, but only reduced survival by <2%. When human factors were included, ‘total’ adult mortality was solely related to harvest; the influence of native carnivores was compensatory. Annual total mortality rates were lowest in populations sympatric with both pumas and wolves because managers reduced female harvest in areas with abundant or diverse carnivores. Mortality from native carnivores peaked in late winter and early spring, while harvest-induced mortality peaked in autumn. The strong peak in harvest-induced mortality during the autumn hunting season decreased as the number of native carnivore species increased. Synthesis and applications. Elevated baseline adult female elk mortality from wolves in years with high winter precipitation could affect elk abundance as

  7. When Your "Problem" Becomes Mine: Adult Female Siblings' Perspectives of Having a Brother with a Disability

    ERIC Educational Resources Information Center

    Pompeo, Michelle N.

    2009-01-01

    This study is a retrospective look at adult female siblings' perspectives of their childhoods and present identities based on having a brother with a disability. This paper focuses on siblings' experiences within educational and public domains, and how such experiences have shaped their personalities and career choices. Qualitative findings were…

  8. Factor Structure Invariance of the Kaufman Adolescent and Adult Intelligence Test across Male and Female Samples

    ERIC Educational Resources Information Center

    Immekus, Jason C.; Maller, Susan J.

    2010-01-01

    Multisample confirmatory factor analysis (MCFA) and latent mean structures analysis (LMS) were used to test measurement invariance and latent mean differences on the Kaufman Adolescent and Adult Intelligence Scale[TM] (KAIT) across males and females in the standardization sample. MCFA found that the parameters of the KAIT two-factor model were…

  9. An Enhanced Pre- and Postnatal Development Study in Cynomolgus Monkeys with Tabalumab: A Human IgG4 Monoclonal Antibody.

    PubMed

    Breslin, William J; Hilbish, Kim G; Martin, Jennifer A; Halstead, Carolyn A; Newcomb, Deanna L; Chellman, Gary J

    2015-06-01

    Tabalumab, a human IgG4 monoclonal antibody (mAb) with neutralizing activity against both soluble and membrane B-cell activating factor (BAFF), has been under development for the treatment of autoimmune diseases. The purpose of this study was to determine the potential adverse effects of maternal tabalumab exposure on pregnancy, parturition, and lactation of the mothers and on the growth, viability, and development of the offspring through postnatal day (PND) 204. Tabalumab was administered by subcutaneous injection to presumed pregnant cynomolgus monkeys (16-19 per group) every 2 weeks from gestation day (GD) 20 to 22 until parturition at doses of 0, 0.3, or 30 mg/kg. Evaluations in mothers and infants included clinical signs, body weight, toxicokinetics, blood lymphocyte phenotyping, T-cell-dependent antibody response (infants only), antitherapeutic antibody (ATA), organ weights (infants only), and gross and microscopic histopathology. Infants were also examined for external and visceral morphologic and neurobehavioral development. There were no adverse tabalumab-related effects on maternal or infant endpoints. An expected pharmacological decrease in peripheral blood B-lymphocytes occurred in adults and infants; however, B-cell recovery was evident by PND154 in adults and infants at 0.3 mg/kg and by PND204 in infants at 30 mg/kg. At 30 mg/kg, a reduced IgM antibody response to T-cell-dependent antigen keyhole limpet hemocyanin (KLH) was observed following primary immunization. Following secondary KLH immunization, all infants in both dose groups mounted anti-KLH IgM and IgG antibody responses similar to control. Placental and mammary transfer of tabalumab was demonstrated. In conclusion, the no-observed-adverse-effect level for maternal and developmental toxicity was 30 mg/kg, the highest dose tested. Exposures at 30 mg/kg provide a margin of safety of 16× the anticipated clinical exposure. © 2015 Wiley Periodicals, Inc.

  10. Selection and Investigation of a Primate Model of Spontaneous Degenerative Knee Osteoarthritis, the Cynomolgus Monkey (Macaca Fascicularis).

    PubMed

    Liu, Gang; Zhang, Lei; Zhou, Xin; Zhang, Bao L; Guo, Guang X; Xu, Ping; Wang, Guo Y; Fu, Shi J

    2018-07-01

    BACKGROUND The aim of this study was to identify a primate model of degenerative knee osteoarthritis (KOA) that may be more relevant for research studies on degenerative KOA in humans. MATERIAL AND METHODS Sixteen specific-pathogen-free (SPF) male cynomolgus monkeys (Macaca fascicularis) were divided into group A (n=8), an old group (22.0-25.3 years of age), and group B (n=8), a young group (3.0-5.2 years of age). For each primate, the behavior was observed, knee circumference was measured, knee joint X-rays were performed, and peripheral blood white blood cell (WBC) counts were measured, and the Kellgren and Lawrence (K-L) system was used for the classification of osteoarthritis. An enzyme-linked immunoassay (ELISA) was performed on knee joint fluid to measure levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)13. Changes in articular cartilage were evaluated using the Brittberg score and the Mankin histopathology grading score, respectively. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot were used to measure the expression of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and the findings in the two groups of primates were compared. RESULTS Seven old aged primates in group A were compared with group B, and showed significant differences in WBC count, synovial fluid IL-1β, TGF-β1, and MMP13 levels, expression levels of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and in the Brittberg and Mankin scores (all, P<0.05). CONCLUSIONS Cynomolgus monkeys (Macaca fascicularis) might be a model for age-related degenerative KOA.

  11. Comparison of the effects of pathogenic simian human immunodeficiency virus strains SHIV-89.6P and SHIV-KU2 in cynomolgus macaques.

    PubMed

    Pawar, Santosh N; Mattila, Joshua T; Sturgeon, Timothy J; Lin, Philana Ling; Narayan, Opendra; Montelaro, Ronald C; Flynn, Joanne L

    2008-04-01

    Factors explaining why human immunodeficiency virus (HIV) enhances the risk of reactivated tuberculosis (TB) are poorly understood. Unfortunately, experimental models of HIV-induced reactivated TB are lacking. We examined whether cynomolgus macaques, which accurately model latent TB in humans, could be used to model pathogenesis of HIV infection in the lungs and associated lymph nodes. These experiments precede studies modeling the effects of HIV infection on latent TB. We infected two groups of macaques with chimeric simian-human immunodeficiency viruses (SHIV-89.6P and SHIV-KU2) and followed viral titers and immunologic parameters including lymphocytes numbers and phenotype in the blood, bronchoalveolar lavage cells, and lymph nodes over the course of infection. Tissues from the lungs, liver, kidney, spleen, and lymph nodes were similarly examined at necropsy. Both strains produced dramatic CD4(+) T cell depletion. Plasma titers were not different between viruses, but we found more SHIV-89.6P in the lungs. Both viruses induced similar patterns of cell activation markers. SHIV-89.6P induced more IFN-gamma expression than SHIV-KU2. These results indicate SHIV-89.6P and SHIV-KU2 infect cynomolgus macaques and may be used to accurately model effects of HIV infection on latent TB.

  12. Differential Effects of Sex Pheromone Compounds on Adult Female Sea Lamprey (Petromyzon marinus) Locomotor Patterns.

    PubMed

    Walaszczyk, Erin J; Goheen, Benjamin B; Steibel, Juan Pedro; Li, Weiming

    2016-06-01

    Synchronization of male and female locomotor activity plays a critical role in ensuring reproductive success, especially in semelparous species. The goal of this study was to elucidate the effects of individual chemical signals, or pheromones, on the locomotor activity in the sea lamprey (Petromyzon marinus). In their native habitat, adult preovulated females (POF) and ovulated females (OF) are exposed to sex pheromone compounds that are released from spermiated males and attract females to nests during their migration and spawning periods. In this study, locomotor activity of individual POF and OF was measured hourly in controlled laboratory conditions using an automated video-tracking system. Differences in the activity between a baseline day (no treatment exposure) and a treatment day (sex pheromone compound or control exposure) were examined for daytime and nighttime periods. Results showed that different pheromone compound treatments affected both POF and OF sea lamprey (p < 0.05) but in different ways. Spermiated male washings (SMW) and one of its main components, 7α,12α,24-trihydroxy-5α-cholan-3-one 24 sulfate (3kPZS), decreased activity of POF during the nighttime. SMW also reduced activity in POF during the daytime. In contrast, SMW increased activity of OF during the daytime, and an additional compound found in SMW, petromyzonol sulfate (PZS), decreased the activity during the nighttime. In addition, we examined factors that allowed us to infer the overall locomotor patterns. SMW increased the maximum hourly activity during the daytime, decreased the maximum hourly activity during the nighttime, and reduced the percentage of nocturnal activity in OF. Our findings suggest that adult females have evolved to respond to different male compounds in regards to their locomotor activity before and after final maturation. This is a rare example of how species-wide chemosensory stimuli can affect not only the amounts of activity but also the overall locomotor

  13. Evaluation of Serum Lipid, Thyroid, and Hepatic Clinical Chemistries in Association With Serum Perfluorooctanesulfonate (PFOS) in Cynomolgus Monkeys After Oral Dosing With Potassium PFOS

    PubMed Central

    Allen, Bruce C.; Andres, Kara L.; Ehresman, David J.; Falvo, Ria; Provencher, Anne; Olsen, Geary W.; Butenhoff, John L.

    2017-01-01

    Abstract An oral dose study with perfluorooctanesulfonate (PFOS) was undertaken to identify potential associations between serum PFOS and changes in serum clinical chemistry parameters in purpose-bred young adult cynomolgus monkeys (Macaca fascicularis). In this study, control group (n = 6/sex) was sham-dosed with vehicle (0.5% Tween 20 and 5% ethanol in water), low-dose group (n = 6/sex) received 1 single K+PFOS dose (9 mg/kg), and high-dose group (n = 4–6/sex) received 3 separate K+ PFOS doses (11–17.2 mg/kg). Monkeys were given routine checkups and observed carefully for health problems on a daily basis. Scheduled blood samples were drawn from all monkeys prior to, during, and after K+PFOS administration for up to 1 year and they were analyzed for PFOS concentrations and clinical chemistry markers for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. No mortality occurred during the study. All the monkeys were healthy, gained weight, and were released back to the colony at the end of the study. The highest serum PFOS achieved was approximately 165 μg/ml. When compared with time-matched controls, administration of K+PFOS to monkeys did not result in any toxicologically meaningful or clinically relevant changes in serum clinical measurements for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. A slight reduction in serum cholesterol (primarily the high-density lipoprotein fraction), although not toxicologically significant, was observed. The corresponding lower-bound fifth percentile benchmark concentrations (BMCL1sd) were 74 and 76 μg/ml for male and female monkeys, respectively. Compared to the 2013–2014 geometric mean serum PFOS level of 4.99 ng/ml (0.00499 μg/ml) in US general population reported by CDC NHANES, this represents 4 orders of magnitude for margin of exposure. PMID:28115654

  14. Self-characterizations of adult female informal caregivers: gender identity and the bearing of burden.

    PubMed

    Kramer, Maeona K

    2005-01-01

    Gender identity is a powerful aspect of self that shapes values, attitudes, and conduct. Family caregivers, particularly women, tend to forgo institutionalization of care recipients even when care demands are overwhelming. The reluctance of women to relinquish care raises questions about the relationship between gender identity and the bearing of burden. To illuminate the relationship between gender and burden, 36 adult women caring for highly dependent adults were asked to describe the nature of "self"; that is, how they characterized themselves as a person. Results were tabulated and critically examined in relation to stereotypical gender traits, as well as social and political processes that create gender dichotomies. Overall, self-characterizations indicated caregivers had internalized stereotypical female gender traits that support and facilitate the enduring of burden.

  15. Balancing Work, Family, and Student Roles: A Phenomenological Study of the Adult Female Graduate Online Learner

    ERIC Educational Resources Information Center

    Rousseau, Charlene X.

    2012-01-01

    The purpose of this phenomenological study was to gain an understanding of the lived experiences of female adult learners pursuing graduate degrees online. As online graduate programs have become increasingly popular and more readily available in the last decade, more women than men are enrolling in online graduate programs in addition to…

  16. Cocaine-induced locomotor activity is increased by prior handling in adolescent but not adult female rats

    PubMed Central

    Maldonado, Antoniette M.; Kirstein, Cheryl L.

    2017-01-01

    Adolescence is a period of transition that is associated with increased levels of stress and a heightened propensity to initiate drug use. Neuronal development is still occurring during this transitional period, which includes the continued development of the dopamine system during the adolescent period. In the present study, the effects of pre-test handling on cocaine-induced locomotor activity were investigated among female adolescent and young adult rats upon presentation to a novel environment. On postnatal days (PND) 41–44 and 56–59 animals were handled (b.i.d.) in the colony room for 3 min. On PND 45 or PND 60, animals were removed from the colony room, weighed, and administered an acute injection of either cocaine or saline and presented to a novel environment where behavior was recorded for 30 min. Adolescent females (PND 45) that were handled prior to cocaine administration demonstrated elevated levels of cocaine-induced activity relative to their age-matched non-handled counterparts and also to their handled-adult counterparts. In contrast, among non-handled animals, young adults (PND 60) exhibited elevated drug-induced locomotion at several time points during the trial. Non-handled adolescent animals demonstrated the previously described “hyporesponsive” behavioral profile relative to their non-handled adult counterparts. The results from the present experiment indicate that adolescent animals may be more sensitive to basic laboratory manipulations such as pre-test handling, and care must be taken when utilizing adolescent animals in behavioral testing. Handling appears to be a sensitive manipulation in elucidating differences in cocaine-induced behavioral activation between ages. PMID:16176824

  17. Developmental origins of pregnancy loss in the adult female common marmoset monkey (Callithrix jacchus).

    PubMed

    Rutherford, Julienne N; deMartelly, Victoria A; Layne Colon, Donna G; Ross, Corinna N; Tardif, Suzette D

    2014-01-01

    The impact of the intrauterine environment on the developmental programming of adult female reproductive success is still poorly understood and potentially underestimated. Litter size variation in a nonhuman primate, the common marmoset monkey (Callithrix jacchus), allows us to model the effects of varying intrauterine environments (e.g. nutrient restriction, exposure to male womb-mates) on the risk of losing fetuses in adulthood. Our previous work has characterized the fetuses of triplet pregnancies as experiencing intrauterine nutritional restriction. We used over a decade of demographic data from the Southwest National Primate Research Center common marmoset colony. We evaluated differences between twin and triplet females in the number of pregnancies they produce and the proportion of those pregnancies that ended in fetal loss. We found that triplet females produced the same number of total offspring as twin females, but lost offspring during pregnancy at a significantly higher rate than did twins (38% vs. 13%, p = 0.02). Regardless of their own birth weight or the sex ratio of the litter the experienced as fetuses, triplet females lost more fetuses than did twins. Females with a male littermate experienced a significant increase in the proportion of stillbirths. These striking findings anchor pregnancy loss in the mother's own fetal environment and development, underscoring a "Womb to Womb" view of the lifecourse and the intergenerational consequences of development. This has important translational implications for understanding the large proportion of human stillbirths that are unexplained. Our findings provide strong evidence that a full understanding of mammalian life history and reproductive biology requires a developmental foundation.

  18. Analysis of Factors Causing Adult Female Learners to Drop out of E-Learning Courses in Korea

    ERIC Educational Resources Information Center

    Kim, Sung-Wan; Park, Soon-Shin

    2015-01-01

    The purpose of this study was to investigate the factors that influence adult female learners' dropout in e-learning courses, and to suggest possible solutions to problem of high dropout rates in Korea. To identify the factors, we analyzed the literature and developed a questionnaire consisting of 9 possible factors and 16 items. Data gathered…

  19. Differences in sperm storage and remating propensity between adult females of two morphotypes of the Anastrepha fraterculus (Diptera: Tephritidae) cryptic species complex.

    PubMed

    Abraham, S; Rull, J; Mendoza, M; Liendo, M C; Devescovi, F; Roriz, A K; Kovaleski, A; Segura, D F; Vera, M T

    2014-06-01

    The South American fruit fly, Anastrepha fraterculus, is a complex of cryptic species composed of at least seven morphotypes. Some of them, such as the Peruvian and Brazilian 1 morphotypes (which include Argentinean populations), exhibit strong pre-copulatory isolation, yet it is possible to obtain heterotypic crosses when forcing copulation of adults under laboratory conditions. The cross involving Peruvian males and Argentinean females produces F1 offspring with reduced viability in terms of egg hatch. This low hatchability could be caused by a reduced amount of sperm transferred to and stored by females mated with heterotypic males, which in turn could affect their post-copulatory behaviour. To test these hypotheses, we investigated sperm transfer and female mating and remating behaviour for homotypic and heterotypic crosses between adults of two morphotypes (Brazilian 1 [Argentina] and Peruvian [Peru]) of the A. fraterculus cryptic species complex. As reported before, Argentinean males and females mated earlier in the day than the other three mating combinations. Peruvian females engaged in shorter copulation times than Argentinean females. Peruvian females tended to store smaller quantities of sperm than Argentinean females, and almost a half of the crosses involving Argentinean males and Peruvian females were unsuccessful (no sperm transfer). However, there was no evidence that the cross between Peruvian males and Argentinean females resulted in storage of a critically small amount of sperm (posing risk of sperm shortage). Argentinean females were more willing to remate than Peruvian females, irrespective of male morphotype, but latency to remating was not affected by male or female morphotype. This study shows that mating behaviour differs between some of the A. fraterculus complex morphotypes, with female but not male morphotype determining female likelihood to remate.

  20. Divergent hypoxia tolerance in adult males and females of the plainfin midshipman (Porichthys notatus).

    PubMed

    LeMoine, Christophe M R; Bucking, Carol; Craig, Paul M; Walsh, Patrick J

    2014-01-01

    In the summer, the plainfin midshipman (Poricththys notatus) migrates to reproduce in the nearshore environment, where oxygen levels are influenced by the tidal cycles. Parental males establish nests under rocks in the intertidal zone, where they reside until the eggs they guard are fully developed. In contrast, females and sneaker males leave the nests shortly after spawning. We examined the physiological resistance and metabolic response of parental male and female adult midshipman to hypoxia to test whether they exhibited sex-specific differences reflecting their reproductive strategies. Further, we assessed whether metabolic enzymes and metabolites were differentially enriched in tissues of parental males and females to explain the differences observed in their hypoxia tolerance. While parental males and females exhibited similar depression of their oxygen consumption in response to graded hypoxia, parental males could withstand significantly longer exposures to severe hypoxic stress. At the biochemical level, parental males showed higher hepatic glycogen reserves and higher glycolytic enzyme capacities in gills and skeletal muscles than females. Although some of these enzymatic variations could be explained by differences in body size, we also observed a significant effect of sex on some of these factors. These results suggest that parental male midshipman may benefit from sexual dimorphism at the whole-organismal (larger body size) and biochemical (enzyme activities) levels, conferring on them a higher glycolytic potential to sustain the extensive hypoxia bouts they experience in nature.

  1. Agreement of SpO2, SaO2 and ScO2 in anesthetized cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Young, Simon S; Skeans, Susan M; Lamca, James E; Chapman, Richard W

    2002-07-01

    To assess the agreement between three measurements of arterial oxygen saturation (SpO 2 , SaO 2 and ScO 2 ) in anesthetized cynomolgus monkeys. Prospective study. Eleven mature, male cynomolgus monkeys (Macaca fasicularis). Monkeys were anesthetized with intramuscular ketamine followed by intravenous propofol. The trachea of each was intubated and the lungs ventilated. Arterial oxygen saturation was measured with a Nonin 8500 V pulse oximeter, using a lingual clip on the cheek. Arterial blood samples were taken from an indwelling catheter. Inspired oxygen concentration was varied from 12 to 20%, and 88 paired arterial blood samples and saturation measurements were taken. Arterial oxygen saturation in the blood samples was measured using a cooximeter. The saturation was also calculated from the arterial oxygen tension using the Adair equation. The results were compared using Bland and Altman's method. The pulse oximeter readings were 2.7% higher than that of the cooximeter, with a limit of agreement of -3.9 to 9.3%. The pulse oximeter readings were 1.8% higher than the calculated saturation, with a limit of agreement of -6.5% to 10.1%. The cooximeter readings were 0.9% lower than the calculated saturation, with a limit of agreement of -5.6% to 3.8%. The agreement between SpO 2 and other measurements of arterial oxygen saturation in this study is typical for this technique. The bias and limits of agreement are consistent with reports in other species. The Nonin 8500 V is a useful pulse oximeter for clinical use in primates. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  2. Mate Choice in Adult Female Bengalese Finches: Females Express Consistent Preferences for Individual Males and Prefer Female-Directed Song Performances

    PubMed Central

    Dunning, Jeffery L.; Pant, Santosh; Bass, Aaron; Coburn, Zachary; Prather, Jonathan F.

    2014-01-01

    In the process of mate selection by female songbirds, male suitors advertise their quality through reproductive displays in which song plays an important role. Females evaluate the quality of each signal and the associated male, and the results of that evaluation guide expression of selective courtship displays. Some studies reveal broad agreement among females in their preferences for specific signal characteristics, indicating that those features are especially salient in female mate choice. Other studies reveal that females differ in their preference for specific characteristics, indicating that in those cases female evaluation of signal quality is influenced by factors other than simply the physical properties of the signal. Thus, both the physical properties of male signals and specific traits of female signal evaluation can impact female mate choice. Here, we characterized the mate preferences of female Bengalese finches. We found that calls and copulation solicitation displays are equally reliable indicators of female preference. In response to songs from an array of males, each female expressed an individual-specific song preference, and those preferences were consistent across tests spanning many months. Across a population of females, songs of some males were more commonly preferred than others, and females preferred female-directed songs more than undirected songs, suggesting that some song features are broadly attractive. Preferences were indistinguishable for females that did or did not have social experience with the singers, indicating that female preference is strongly directed by song features rather than experiences associated with the singer. Analysis of song properties revealed several candidate parameters that may influence female evaluation. In an initial investigation of those parameters, females could be very selective for one song feature yet not selective for another. Therefore, multiple song parameters are evaluated independently

  3. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring.

    PubMed

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A

    2016-04-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Effects of Adult Female Rat Androgenization on Brain Morphology and Metabolomic Profile.

    PubMed

    Perez-Laso, Carmen; Cerdan, Sebastián; Junque, Carme; Gómez, Ángel; Ortega, Esperanza; Mora, Mireia; Avendaño, Carlos; Gómez-Gil, Esther; Del Cerro, María Cruz Rodríguez; Guillamon, Antonio

    2017-07-06

    Androgenization in adult natal women, as in transsexual men (TM), affects brain cortical thickness and the volume of subcortical structures. In order to understand the mechanism underlying these changes we have developed an adult female rat model of androgenization. Magnetic resonance imaging and spectroscopy were used to monitor brain volume changes, white matter microstructure and ex vivo metabolic profiles over 32 days in androgenized and control subjects. Supraphysiological doses of testosterone prevents aging decrease of fractional anisotropy values, decreased general cortical volume and the relative concentrations of glutamine (Gln) and myo-Inositol (mI). An increase in the N-acetylaspartate (NAA)/mI ratio was detected d. Since mI and Gln are astrocyte markers and osmolytes, we suspect that the anabolic effects of testosterone change astrocyte osmolarity so as to extrude Mi and Gln from these cells in order to maintain osmotic homeostasis. This mechanism could explain the brain changes observed in TM and other individuals receiving androgenic anabolic steroids. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

    PubMed Central

    Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

    2016-01-01

    Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

  6. Developmental Origins of Pregnancy Loss in the Adult Female Common Marmoset Monkey (Callithrix jacchus)

    PubMed Central

    Rutherford, Julienne N.; deMartelly, Victoria A.; Layne Colon, Donna G.; Ross, Corinna N.; Tardif, Suzette D.

    2014-01-01

    Background The impact of the intrauterine environment on the developmental programming of adult female reproductive success is still poorly understood and potentially underestimated. Litter size variation in a nonhuman primate, the common marmoset monkey (Callithrix jacchus), allows us to model the effects of varying intrauterine environments (e.g. nutrient restriction, exposure to male womb-mates) on the risk of losing fetuses in adulthood. Our previous work has characterized the fetuses of triplet pregnancies as experiencing intrauterine nutritional restriction. Methodology/Principal Findings We used over a decade of demographic data from the Southwest National Primate Research Center common marmoset colony. We evaluated differences between twin and triplet females in the number of pregnancies they produce and the proportion of those pregnancies that ended in fetal loss. We found that triplet females produced the same number of total offspring as twin females, but lost offspring during pregnancy at a significantly higher rate than did twins (38% vs. 13%, p = 0.02). Regardless of their own birth weight or the sex ratio of the litter the experienced as fetuses, triplet females lost more fetuses than did twins. Females with a male littermate experienced a significant increase in the proportion of stillbirths. Conclusions/Significance These striking findings anchor pregnancy loss in the mother’s own fetal environment and development, underscoring a "Womb to Womb" view of the lifecourse and the intergenerational consequences of development. This has important translational implications for understanding the large proportion of human stillbirths that are unexplained. Our findings provide strong evidence that a full understanding of mammalian life history and reproductive biology requires a developmental foundation. PMID:24871614

  7. Finite Element Analysis of Denosumab Treatment Effects on Vertebral Strength in Ovariectomized Cynomolgus Monkeys.

    PubMed

    Lee, David C; Varela, Aurore; Kostenuik, Paul J; Ominsky, Michael S; Keaveny, Tony M

    2016-08-01

    Finite element analysis has not yet been validated for measuring changes in whole-bone strength at the hip or spine in people after treatment with an osteoporosis agent. Toward that end, we assessed the ability of a clinically approved implementation of finite element analysis to correctly quantify treatment effects on vertebral strength, comparing against direct mechanical testing, in cynomolgus monkeys randomly assigned to one of three 16-month-long treatments: sham surgery with vehicle (Sham-Vehicle), ovariectomy with vehicle (OVX-Vehicle), or ovariectomy with denosumab (OVX-DMAb). After treatment, T12 vertebrae were retrieved, scanned with micro-CT, and mechanically tested to measure compressive strength. Blinded to the strength data and treatment codes, the micro-CT images were coarsened and homogenized to create continuum-type finite element models, without explicit porosity. With clinical translation in mind, these models were then analyzed for strength using the U.S. Food and Drug Administration (FDA)-cleared VirtuOst software application (O.N. Diagnostics, Berkeley, CA, USA), developed for analysis of human bones. We found that vertebral strength by finite element analysis was highly correlated (R(2)  = 0.97; n = 52) with mechanical testing, independent of treatment (p = 0.12). Further, the size of the treatment effect on strength (ratio of mean OVX-DMAb to mean OVX-Vehicle, as a percentage) was large and did not differ (p = 0.79) between mechanical testing (+57%; 95% CI [26%, 95%]) and finite element analysis (+51% [20%, 88%]). The micro-CT analysis revealed increases in cortical thickness (+45% [19%, 73%]) and trabecular bone volume fraction (+24% [8%, 42%]). These results show that a preestablished clinical finite element analysis implementation-developed for human bone and clinically validated in fracture-outcome studies-correctly quantified the observed treatment effects of denosumab on vertebral strength in cynomolgus monkeys. One

  8. Female Adult Learners in Rural Community Colleges: A Case Study of Role Perception and Navigation for Student Mothers

    ERIC Educational Resources Information Center

    Thompson, Tara Lynn

    2013-01-01

    Female adult learners, the fastest growing subpopulation in community colleges, face challenges navigating domestic, professional, and academic roles and take time off from school to reconcile issues with multiple role navigation; thus, their education is disjointed and staggered, creating barriers to persistence. This interpretive design…

  9. Blood vitamin D(3) metabolite concentrations of adult female bearded dragons (Pogona vitticeps) remain stable after ceasing UVb exposure.

    PubMed

    Oonincx, D G A B; van de Wal, M D; Bosch, G; Stumpel, J B G; Heijboer, A C; van Leeuwen, J P T M; Hendriks, W H; Kik, M

    2013-07-01

    Vitamin D deficiency can lead to several health problems collectively called metabolic bone disease (MBD). One commonly kept reptile species prone to develop MBD if managed incorrectly is the bearded dragon (Pogona vitticeps). This study aimed to determine the extent to which adult female bearded dragons fed a diet low in vitamin D can use stored vitamin D and its metabolites to maintain plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations after discontinuing UVb exposure. Blood samples of healthy adult female bearded dragons, exposed to UVb radiation for over 6 months were collected (day 0) after which UVb exposure was discontinued for 83 days and blood was collected. Blood plasma was analysed for concentrations of total Ca, total P, ionized Ca, uric acid, 25(OH)D(3) and 1,25(OH)(2)D(3). There was no significant change in plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations during the study. While total Ca and P in whole blood was found to significantly decrease over time (P < 0.0088 and 0.0016, respectively), values were within the reference range. Plasma ionized Ca tended (P = 0.0525) to decrease during the study. Adult female bearded dragons, previously exposed to UVb, are able to maintain blood vitamin D metabolite concentrations when UVb exposure is discontinued for a period of up to 83 days. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Standardization of magnetocardiography in nonhuman primates

    NASA Astrophysics Data System (ADS)

    Seki, Yusuke; Muneyuki, Kenta; Kandori, Akihiko; Tsukada, Keiji; Terao, Keiji; Ageyama, Naohide

    2008-03-01

    To establish the electrophysiological mappings of nonhuman primates by using magnetocardiogram (MCG) data and obtain the normal values of MCG parameters, we used 64-channel superconducting quantum interference devices to measure 8 × 8 MCG data for 95 cynomolgus monkeys (Macaca fascicularis, 51 female and 44 male). The PQ interval, QRS duration, QT interval and QTc were respectively 79 ± 14 ms, 42 ± 7 ms, 222 ± 23 ms and 363 ± 25 (mean ± SD), and these parameters did not differ significantly between female and male monkeys. These results indicate the normal values of the MCG parameters of the cynomolgus monkey and should facilitate animal experiments in magnetocardiography.

  11. Smooth-muscle-specific gene transfer with the human maxi-k channel improves erectile function and enhances sexual behavior in atherosclerotic cynomolgus monkeys.

    PubMed

    Christ, George J; Andersson, Karl-Erik; Williams, Koudy; Zhao, Weixin; D'Agostino, Ralph; Kaplan, Jay; Aboushwareb, Tamer; Yoo, James; Calenda, Giulia; Davies, Kelvin P; Sellers, Rani S; Melman, Arnold

    2009-12-01

    Despite the advent of effective oral therapies for erectile dysfunction (ED), many patients are not successfully treated, and side effects have been documented. To further evaluate the potential utility of naked DNA-based gene transfer as an attractive treatment option for ED. The effects of gene transfer on erectile function and sexual behavior were evaluated in eight male cynomolgus monkeys with ED secondary to moderately severe, diet-induced atherosclerosis. Following establishment of baseline characteristics, animals were subjected to intracavernous injection of a smooth-muscle-specific gene transfer vector (pSMAA-hSlo) encoding the pore-forming subunit of the human large-conductance, calcium-sensitive potassium channel (Maxi-K). For the sexual behavior studies, 2 wk of baseline data were obtained, and then animals were placed in the presence of estrogen-implanted females (n=2) three times per week for 30 min, and sexual behavior was recorded. The intracavernous pressure response to papaverine injection was also monitored. Dramatic changes in erectile function and sexual behavior were observed after intracorporal gene transfer. The frequency of partial (6±2 to 10±2) and full (2±1.5 to 5±1.4) erections were significantly increased, with a parallel 2-3-fold increase in the duration of the observed erections. The frequency and latency of ejaculation were increased and decreased, respectively. Frequency and duration of grooming by the female were increased, and the latency decreased. Increased latency and decreased frequency of body contact was also observed, and this is characteristic of the typical drop in consort intimacy that occurs after mating in most macaque species. In addition, an increased responsiveness to intracavernous papaverine injection was observed. The data indicate that intracorporal Maxi-K-channel gene transfer enhances erectile capacity and sexual behavior; the data imply that increased erectile function per se may lead to increased sexual

  12. Transcriptome of the adult female malaria mosquito vector Anopheles albimanus.

    PubMed

    Martínez-Barnetche, Jesús; Gómez-Barreto, Rosa E; Ovilla-Muñoz, Marbella; Téllez-Sosa, Juan; García López, David E; Dinglasan, Rhoel R; Ubaida Mohien, Ceereena; MacCallum, Robert M; Redmond, Seth N; Gibbons, John G; Rokas, Antonis; Machado, Carlos A; Cazares-Raga, Febe E; González-Cerón, Lilia; Hernández-Martínez, Salvador; Rodríguez López, Mario H

    2012-05-30

    Human Malaria is transmitted by mosquitoes of the genus Anopheles. Transmission is a complex phenomenon involving biological and environmental factors of humans, parasites and mosquitoes. Among more than 500 anopheline species, only a few species from different branches of the mosquito evolutionary tree transmit malaria, suggesting that their vectorial capacity has evolved independently. Anopheles albimanus (subgenus Nyssorhynchus) is an important malaria vector in the Americas. The divergence time between Anopheles gambiae, the main malaria vector in Africa, and the Neotropical vectors has been estimated to be 100 My. To better understand the biological basis of malaria transmission and to develop novel and effective means of vector control, there is a need to explore the mosquito biology beyond the An. gambiae complex. We sequenced the transcriptome of the An. albimanus adult female. By combining Sanger, 454 and Illumina sequences from cDNA libraries derived from the midgut, cuticular fat body, dorsal vessel, salivary gland and whole body, we generated a single, high-quality assembly containing 16,669 transcripts, 92% of which mapped to the An. darlingi genome and covered 90% of the core eukaryotic genome. Bidirectional comparisons between the An. gambiae, An. darlingi and An. albimanus predicted proteomes allowed the identification of 3,772 putative orthologs. More than half of the transcripts had a match to proteins in other insect vectors and had an InterPro annotation. We identified several protein families that may be relevant to the study of Plasmodium-mosquito interaction. An open source transcript annotation browser called GDAV (Genome-Delinked Annotation Viewer) was developed to facilitate public access to the data generated by this and future transcriptome projects. We have explored the adult female transcriptome of one important New World malaria vector, An. albimanus. We identified protein-coding transcripts involved in biological processes that may

  13. Elevated androstenedione in young adult but not early adolescent prenatally androgenized female rats.

    PubMed

    Shah, Ami B; Nivar, Isaac; Speelman, Diana L

    2018-01-01

    Elevated testosterone (T) is routinely reported as a marker of hyperandrogenemia in rodent models for polycystic ovary syndrome (PCOS). In women with PCOS, elevated serum androstenedione (A4) is associated with more severe phenotypes, including a positive correlation with serum T, DHEAS, free androgen index (FAI), LH, and LH/FSH ratio. Furthermore, A4, along with calculated free T and FAI, was identified as one of the best predictors of PCOS in adult women of all ages (18 to > 50 y). The objective of this study was to investigate serum A4 levels in early adolescent and young adult prenatally androgenized (PNA) female rats, a model for PCOS. Pregnant rats were injected with 5 mg T daily during gestational days 16-19 (PNA rats, experimental group) or an equal volume of vehicle (control group). Female offspring of both groups had tail vein blood drawn for serum analysis at 8 and 16 weeks of age. ELISAs were used to quantify serum A4 and T levels. Serum A4 and T were elevated in 16-week-old PNA rats compared to controls. There was no significant difference in either hormone at 8 weeks of age. The PNA rats demonstrated elevated serum A4 and T in young adulthood, as has been observed in women with PCOS, further validating this as a model for PCOS and underscoring the importance of serum A4 elevation as a parameter inherent to PCOS and a rodent model for the disorder. Significant A4 elevation develops between early adolescence and early adulthood in this PNA rat model.

  14. Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats.

    PubMed

    Trejter, Marcin; Jopek, Karol; Celichowski, Piotr; Tyczewska, Marianna; Malendowicz, Ludwik K; Rucinski, Marcin

    2015-01-01

    Adrenocortical activity in various species is sensitive to androgens and estrogens. They may affect adrenal cortex growth and functioning either via central pathways (CRH and ACTH) or directly, via specific receptors expressed in the cortex and/or by interfering with adrenocortical enzymes, among them those involved in steroidogenesis. Only limited data on expression of androgen and estrogen receptors in adrenal glands are available. Therefore the present study aimed to characterize, at the level of mRNA, expression of these receptors in specific components of adrenal cortex of intact adult male and female rats. Studies were performed on adult male and female (estrus) Wistar rats. Total RNA was isolated from adrenal zona glomerulosa (ZG) and fasciculate/reticularis (ZF/R). Expression of genes were evaluated by means of Affymetrix® Rat Gene 1.1 ST Array Strip and QPCR. By means of Affymetrix® Rat Gene 1.1 ST Array we examined adrenocortical sex differences in the expression of nearly 30,000 genes. All data were analyzed in relation to the adrenals of the male rats. 32 genes were differentially expressed in ZG, and 233 genes in ZF/R. In the ZG expression levels of 24 genes were lower and 8 higher in female rats. The more distinct sex differences were observed in the ZF/R, in which expression levels of 146 genes were lower and 87 genes higher in female rats. Performed analyses did not reveal sex differences in the expression levels of both androgen (AR) and estrogen (ER) receptor genes in the adrenal cortex of male and female rats. Therefore matrix data were validated by QPCR. QPCR revealed higher expression levels of AR gene both in ZG and ZF/R of male than female rats. On the other hand, QPCR did not reveal sex-related differences in the expression levels of ERα, ERβ and non-genomic GPR30 (GPER-1) receptor. Of those genes expression levels of ERα genes were the highest. In studied adrenal samples the relative expression of ERα mRNA was higher than ERβ m

  15. Flight Capacity of Bactrocera dorsalis (Diptera: Tephritidae) Adult Females Based on Flight Mill Studies and Flight Muscle Ultrastructure

    PubMed Central

    Chen, Peng; Yuan, Ruiling; Wang, Xiaowei; Xu, Jin

    2015-01-01

    The oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), is considered a major economic threat in many regions worldwide. To better comprehend flight capacity of B. dorsalis and its physiological basis, a computer-monitored flight mill was used to study flight capacity of B. dorsalis adult females of various ages, and the changes of its flight muscle ultrastructures were studied by transmission electron microscopy. The flight capacity (both speed and distance) changed significantly with age of B. dorsalis female adults, peaking at about 15 d; the myofibril diameter of the flight muscle of test insects at 15-d old was the longest, up to 1.56 µm, the sarcomere length at 15-d old was the shortest, averaging at 1.37 µm, volume content of mitochondria of flight muscle at 15-d old reached the peak, it was 32.64%. This study provides the important scientific data for better revealing long-distance movement mechanism of B. dorsalis. PMID:26450591

  16. Reproductive development of male goat kids reared with or without permanent contact with adult females until 10 months of age.

    PubMed

    Lacuesta, L; Orihuela, A; Ungerfeld, R

    2015-01-01

    Adult male ruminants that were reared in contact with females display greater sexual behavior than those reared in single male groups. The aim of the experiment was to compare the reproductive development of prepubertal male kids reared with or without direct permanent contact with adult females until they were 10 months old. Seventeen Saanen male kids were maintained in two groups until 44 weeks of age: kids reared in permanent direct contact with four adult goats (group FEM, N = 8) and kids that remained isolated from females (group ISO, N = 9). All goats in the FEM group became pregnant approximately when bucks attained 28 weeks of age. Scrotal circumference and testosterone concentration were measured, and semen was obtained by electroejaculation to avoid female contact in the ISO group. Scrotal circumference was greater in FEM kids at 12 and 14 weeks of age (P < 0.0001) and testosterone when they were 20 and 22 weeks old (P < 0.0001). Testosterone concentration was greater in ISO kids from 28 to 44 weeks of age. All semen characteristics increased with age (P < 0.0001). Individual motility was greater in FEM kids than that in ISO kids at 15 and 17 weeks (P < 0.005); mass motility was greater in ISO than that in FEM kids at 32 weeks (P < 0.05); total number of spermatozoa/ejaculate was greater in ISO kids at 30, 32, and 40 weeks and in FEM kids at 43 weeks (P < 0.005); total number of motile spermatozoa was greater in ISO kids at 32 and 40 weeks, whereas at 43 weeks, it was greater in FEM kids (P < 0.005). It was concluded that permanent contact with adult goats had transient and short-time positive effects in male kids' reproductive traits during prepubertal development. However, positive effects stopped after goats used as stimulus became pregnant. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Motivational dynamics underlying eating regulation in young and adult female dieters: relationships with healthy eating behaviours and disordered eating symptoms.

    PubMed

    Verstuyf, Joke; Vansteenkiste, Maarten; Soetens, Barbara; Soenens, Bart

    2016-06-01

    To investigate whether type of goals and motives underlying females' eating regulation are associated differentially with daily eating behaviours, dependent upon weight and age category. 99 late adolescent female dieters (Mage = 18.94) and 98 adult female dieters (Mage = 45.06), 23.6% of which were overweight, completed a questionnaire and a 7-day diary assessment. Descriptive analysis and path analysis were performed to investigate the research questions. Healthy eating behaviours (HEHS), drive for thinness and binge eating symptoms (EDI). Appearance-focused and controlled eating regulation were positively related to disordered eating symptoms throughout the week. In contrast, autonomous and health-focused eating regulation were associated positively with healthy eating behaviours and were either related negatively or unrelated to disordered eating symptoms. Mean level differences in motivation and eating behaviours emerged according to age and weight status. However, the examined structural model was similar for late adolescent and adult dieters and only few differences emerged between normal-weight and overweight dieters. Dieters' type of motivation helps to explain when eating regulation relates to healthy and disordered eating symptoms.

  18. Salivary testosterone measurement by liquid chromatography tandem mass spectrometry in adult males and females.

    PubMed

    Keevil, B G; MacDonald, P; Macdowall, W; Lee, D M; Wu, F C W

    2014-05-01

    Salivary testosterone (Sal-T) may be a useful surrogate of serum free testosterone. The study aims were to use a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) assay to determine whether Sal-T concentrations accurately reflect Sal-T concentrations in both sexes and to investigate practical aspects of sample collection. Saliva and serum samples were collected in 104 male and 91 female subjects. A more sensitive LC-MS/MS assay was developed to enable Sal-T quantitation in the low concentrations found in females. Saliva (200 µL) was extracted with 1 mL of methyl-tert-butyl ether following the addition of D5-testosterone. Quantitation was performed using a Waters TQ-S mass spectrometer. The assay achieved a lower limit of quantification of 5 pmol/L, sufficiently sensitive to measure testosterone in female saliva. Sal-T showed a diurnal variation but samples taken at weekly and monthly intervals showed no significant differences. Sal-T was stable at ambient temperature for up to 5 days, after freeze-thawing and 3 years frozen storage. Reference intervals for Sal-T were 93-378 pmol/L in males and 5-46 pmol/L in females. Sal-T correlated significantly with serum calculated free-T in males (r = 0.71, P < 0.001) and in females (r = 0.39, P < 0.001). These results confirm that testosterone can be reliably and accurately measured by LC-MS/MS in both adult male and female saliva samples. These results lay the foundation for further exploration of the clinical application of Sal- T as a reliable alternative to serum testosterone in the diagnosis and management of androgen disorders and assessment of androgen status in clinical research.

  19. Inter-segmental motions of the foot: differences between younger and older healthy adult females.

    PubMed

    Lee, Dong Yeon; Seo, Sang Gyo; Kim, Eo Jin; Lee, Doo Jae; Bae, Kee Jeong; Lee, Kyoung Min; Choi, In Ho

    2017-01-01

    Although accumulative evidence exists that support the applicability of multi-segmental foot models (MFMs) in evaluating foot motion in various pathologic conditions, little is known of the effect of aging on inter-segmental foot motion. The objective of this study was to evaluate differences in inter-segmental motion of the foot between older and younger adult healthy females during gait using a MFM with 15-marker set. One hundred symptom-free females, who had no radiographic evidence of osteoarthritis, were evaluated using MFM with 15-marker set. They were divided into young ( n  = 50, 20-35 years old) and old ( n  = 50, 60-69 years old) groups. Coefficients of multiple correlations were evaluated to assess the similarity of kinematic curve. Inter-segmental angles (hindfoot, forefoot, and hallux) were calculated at each gait phase. To evaluate the effect of gait speed on intersegmental foot motion, subgroup analysis was performed according to the similar speed of walking. Kinematic curves showed good or excellent similarity in most parameters. Range of motion in the sagittal ( p  < 0.001) and transverse ( p  = 0.001) plane of the hallux, and sagittal ( p  = 0.023) plane of the forefoot was lower in older females. The dorsiflexion ( p  = 0.001) of the hallux at terminal stance and pre-swing phases was significantly lower in older females. When we compared young and older females with similar speed, these differences remained. Although the overall kinematic pattern was similar between young and older females, reduced range of inter-segmental motion was observed in the older group. Our results suggest that age-related changes need to be considered in studies evaluating inter-segmental motion of the foot.

  20. Peripubertal Vitamin D3 Deficiency Delays Puberty and Disrupts the Estrous Cycle in Adult Female Mice1

    PubMed Central

    Dicken, Cary L.; Israel, Davelene D.; Davis, Joe B.; Sun, Yan; Shu, Jun; Hardin, John; Neal-Perry, Genevieve

    2012-01-01

    ABSTRACT The mechanism(s) by which vitamin D3 regulates female reproduction is minimally understood. We tested the hypothesis that peripubertal vitamin D3 deficiency disrupts hypothalamic-pituitary-ovarian physiology. To test this hypothesis, we used wild-type mice and Cyp27b1 (the rate-limiting enzyme in the synthesis of 1,25-dihydroxyvitamin D3) null mice to study the effect of vitamin D3 deficiency on puberty and reproductive physiology. At the time of weaning, mice were randomized to a vitamin D3-replete or -deficient diet supplemented with calcium. We assessed the age of vaginal opening and first estrus (puberty markers), gonadotropin levels, ovarian histology, ovarian responsiveness to exogenous gonadotropins, and estrous cyclicity. Peripubertal vitamin D3 deficiency significantly delayed vaginal opening without affecting the number of GnRH-immunopositive neurons or estradiol-negative feedback on gonadotropin levels during diestrus. Young adult females maintained on a vitamin D3-deficient diet after puberty had arrested follicular development and prolonged estrous cycles characterized by extended periods of diestrus. Ovaries of vitamin D3-deficient Cyp27b1 null mice responded to exogenous gonadotropins and deposited significantly more oocytes into the oviducts than mice maintained on a vitamin D3-replete diet. Estrous cycles were restored when vitamin D3-deficient Cyp27b1 null young adult females were transferred to a vitamin D3-replete diet. This study is the first to demonstrate that peripubertal vitamin D3 sufficiency is important for an appropriately timed pubertal transition and maintenance of normal female reproductive physiology. These data suggest vitamin D3 is a key regulator of neuroendocrine and ovarian physiology. PMID:22572998

  1. Interleukin-13 neutralization by two distinct receptor blocking mechanisms reduces immunoglobulin E responses and lung inflammation in cynomolgus monkeys.

    PubMed

    Kasaian, Marion T; Tan, Xiang-Yang; Jin, Macy; Fitz, Lori; Marquette, Kimberly; Wood, Nancy; Cook, Timothy A; Lee, Julie; Widom, Angela; Agostinelli, Rita; Bree, Andrea; Schlerman, Franklin J; Olland, Stephane; Wadanoli, Michael; Sypek, Joseph; Gill, Davinder; Goldman, Samuel J; Tchistiakova, Lioudmila

    2008-06-01

    Interleukin (IL)-13 is a key cytokine driving allergic and asthmatic responses and contributes to airway inflammation in cynomolgus monkeys after segmental challenge with Ascaris suum antigen. IL-13 bioactivity is mediated by a heterodimeric receptor (IL-13Ralpha1/IL-4Ralpha) and can be inhibited in vitro by targeting IL-13 interaction with either chain. However, in cytokine systems, in vitro neutralization activity may not always predict inhibitory function in vivo. To address the efficacy of two different IL-13 neutralization mechanisms in a primate model of atopic disease, two humanized monoclonal antibodies to IL-13 were generated, with highly homologous properties, differing in epitope recognition. Ab01 blocks IL-13 interaction with IL-4Ralpha, and Ab02 blocks IL-13 interaction with IL-13Ralpha1. In a cynomolgus monkey model of IgE responses to A. suum antigen, both Ab01 and Ab02 effectively reduced serum titers of Ascaris-specific IgE and diminished ex vivo Ascaris-triggered basophil histamine release, assayed 8 weeks after a single administration of antibody. The two antibodies also produced comparable reductions in pulmonary inflammation after lung segmental challenge with Ascaris antigen. Increased serum levels of IL-13, lacking demonstrable biological activity, were seen postchallenge in animals given either anti-IL-13 antibody but not in control animals given human IgG of irrelevant specificity. These findings demonstrate a potent effect of IL-13 neutralization on IgE-mediated atopic responses in a primate system and show that IL-13 can be efficiently neutralized by targeting either the IL-4Ralpha-binding epitope or the IL-13Ralpha1-binding epitope.

  2. The influence of infant-caregiver experiences on amygdala Bdnf, OXTr, and NPY expression in developing and adult male and female rats.

    PubMed

    Hill, Kathryn T; Warren, Megan; Roth, Tania L

    2014-10-01

    Previous work with various animal models has demonstrated that alterations in the caregiving environment produce long-term changes in anxiety-related and social behaviors, as well as amygdala gene expression. We previously introduced a rodent model in which the timing and duration of exposure to maltreatment or nurturing care outside the home cage can be controlled to assess neurobiological outcomes. Here we sought to determine whether our brief experimental conditions produce changes in gene expression within the developing and adult amygdala. Using a candidate gene approach, we examined fold mRNA changes for the Brain-derived neurotrophic factor (Bdnf), Oxytocin receptor (OXTr), and Neuropeptide Y (NPY) genes, which are all highly expressed in the amygdala and play important roles in anxiety-related and social behaviors. In adults, significant group differences were detected for only Bdnf, with higher levels of Bdnf mRNA for females that had been exposed to maltreatment and males exposed to nurturing care outside the home cage relative to littermate controls. For pups, significant group differences were detected for only OXTr, with lower levels of OXTr mRNA in females exposed to maltreatment. Finally, for adolescents, maltreated-females showed significant changes in Bdnf (decreased), OXTr (decreased), and NPY (increased) mRNA relative to controls. These data illustrate the ability of brief, but repeated exposure to different caregiving environments during the first postnatal week to have long-term effects on gene expression within the developing and adult amygdala, especially for females. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Teriparatide versus low-dose bisphosphonates before and after surgery for adult spinal deformity in female Japanese patients with osteoporosis.

    PubMed

    Seki, Shoji; Hirano, Norikazu; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Suzuki, Kayo; Watanabe, Kenta; Makino, Hiroto; Kanamori, Masahiko; Kimura, Tomoatsu

    2017-08-01

    Complications of adult spinal deformity surgery are problematic in osteoporotic individuals. We compared outcomes between Japanese patients treated perioperatively with teriparatide vs. low-dose bisphosphonates. Fifty-eight osteoporotic adult Japanese female patients were enrolled and assigned to perioperative teriparatide (33 patients) and bisphosphonate (25 patients) groups in non-blinded fashion. Pre- and post-operative X-ray and computed tomography imaging were used to assess outcome, and rates were compared between the groups and according to age. Pain scores and Oswestry Disability Indices (ODI) were calculated before and 2 years after surgery. Adjacent vertebral fractures and implant failure, fusion failure, and poor pain and ODI outcomes were significantly more common in the bisphosphonates group than the teriparatide group. Perioperative administration of teriparatide is more effective than that of low-dose bisphosphonates in preventing complications and maintaining fusion rates in osteoporotic Japanese females with spinal deformities undergoing surgery.

  4. Effects of azadirachtin on the biology of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) adult female, the main vector of American visceral leishmaniasis.

    PubMed

    De Andrade-Coelho, Cláudia Alves; De Souza, Nataly Araujo; Silva, Vanderlei Campos; Souza, Adelson A; Gonzalez, Marcelo Salabert; Rangel, Elizabeth Ferreira

    2014-07-01

    The effects of azadirachtin A added to the sucrose diet of the adult females on the mortality, oviposition, and hatching of the sand fly vector of American visceral leishmaniasis Lutzomyia longipalpis (Lutz & Neiva, 1912) were investigated. Concentrations of 0.1, 1.0, and 10.0 microg/mg of azadirachtin significantly increased insect mortality in comparison with control insects. The same dose also significantly reduced oviposition but not hatching. After a long development period, significantly fewer adult insects were obtained from eggs hatching by azadirachtin-treated females in a dose-response manner. These results indicate that azadirachtin is a potent sterilizer that could be used against the development of Lu. longipalpis populations and as a tool for studying physiological and biochemical processes in phlebotomine species.

  5. Longitudinal changes in reproductive hormones and menstrual cyclicity in cynomolgus monkeys during strenuous exercise training: abrupt transition to exercise-induced amenorrhea.

    PubMed

    Williams, N I; Caston-Balderrama, A L; Helmreich, D L; Parfitt, D B; Nosbisch, C; Cameron, J L

    2001-06-01

    Cross-sectional studies of exercise-induced reproductive dysfunction have documented a high proportion of menstrual cycle disturbances in women involved in strenuous exercise training. However, longitudinal studies have been needed to examine individual susceptibility to exercise-induced reproductive dysfunction and to elucidate the progression of changes in reproductive function that occur with strenuous exercise training. Using the female cynomolgus monkey (Macaca fascicularis), we documented changes in menstrual cyclicity and patterns of LH, FSH, estradiol, and progesterone secretion as the animals developed exercise-induced amenorrhea. As monkeys gradually increased running to 12.3 +/- 0.9 km/day, body weight did not change significantly although food intake remained constant. The time spent training until amenorrhea developed varied widely among animals (7-24 months; mean = 14.3 +/- 2.2 months) and was not correlated with initial body weight, training distance, or food intake. Consistent changes in function of the reproductive axis occurred abruptly, one to two menstrual cycles before the development of amenorrhea. These included significant declines in plasma reproductive hormone concentrations, an increase in follicular phase length, and a decrease in luteal phase progesterone secretion. These data document a high level of interindividual variability in the development of exercise-induced reproductive dysfunction, delineate the progression of changes in reproductive hormone secretion that occur with exercise training, and illustrate an abrupt transition from normal cyclicity to an amenorrheic state in exercising individuals, that is not necessarily associated with weight loss.

  6. Single-cell transcriptome of early embryos and cultured embryonic stem cells of cynomolgus monkeys

    PubMed Central

    Nakamura, Tomonori; Yabuta, Yukihiro; Okamoto, Ikuhiro; Sasaki, Kotaro; Iwatani, Chizuru; Tsuchiya, Hideaki; Saitou, Mitinori

    2017-01-01

    In mammals, the development of pluripotency and specification of primordial germ cells (PGCs) have been studied predominantly using mice as a model organism. However, divergences among mammalian species for such processes have begun to be recognized. Between humans and mice, pre-implantation development appears relatively similar, but the manner and morphology of post-implantation development are significantly different. Nevertheless, the embryogenesis just after implantation in primates, including the specification of PGCs, has been unexplored due to the difficulties in analyzing the embryos at relevant developmental stages. Here, we present a comprehensive single-cell transcriptome dataset of pre- and early post-implantation embryo cells, PGCs and embryonic stem cells (ESCs) of cynomolgus monkeys as a model of higher primates. The identities of each transcriptome were also validated rigorously by other way such as immunofluorescent analysis. The information reported here will serve as a foundation for our understanding of a wide range of processes in the developmental biology of primates, including humans. PMID:28649393

  7. Comparison of Saliva Collection Methods for the Determination of Salivary Cortisol Levels in Rhesus Macaques (Macaca mulatta), Cynomolgus Macaques (Macaca fascicularis), and African Green Monkeys (Chlorocebus aethiops)

    PubMed Central

    Rapp-Santos, Kamala J; Altamura, Louis A; Norris, Sarah L; Lugo-Roman, Luis A; Rico, Pedro J; Hofer, Christian C

    2017-01-01

    The ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of NHP. In this study, 2 methods of collecting saliva (a commercial collection device and passive drool) and the resulting free salivary cortisol levels were compared with total serum cortisol concentration in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis) and African green monkeys (Chlorocebus aethiops) at 2 collection time points. Serum and salivary cortisol levels were determined using a competitive quantitative ELISA. In addition, both saliva collection methods were evaluated for volume collected and ease of use. Compared with passive drool, the experimental collection device was more reliable in collecting sufficient volumes of saliva, and the resulting salivary cortisol values demonstrated stronger correlation with serum cortisol concentration in all species and collection days except cynomolgus macaques on day 1. This saliva collection device allows quick and reliable sample collection for the determination of salivary cortisol levels. In addition, the results might provide a useful tool for evaluating hypothalamic-pituitary-adrenal axis activity or the physiologic stress reaction in NHP as well as a biomarker of psychologic stress states in a variety of situations. PMID:28315649

  8. The Sun, Moon, Wind, and Biological Imperative–Shaping Contrasting Wintertime Migration and Foraging Strategies of Adult Male and Female Northern Fur Seals (Callorhinus ursinus)

    PubMed Central

    Sterling, Jeremy T; Springer, Alan M.; Iverson, Sara J.; Johnson, Shawn P.; Pelland, Noel A.; Johnson, Devin S.; Lea, Mary-Anne; Bond, Nicholas A.

    2014-01-01

    Adult male and female northern fur seals (Callorhinus ursinus) are sexually segregated in different regions of the North Pacific Ocean and Bering Sea during their winter migration. Explanations for this involve interplay between physiology, predator-prey dynamics, and ecosystem characteristics, however possible mechanisms lack empirical support. To investigate factors influencing the winter ecology of both sexes, we deployed five satellite-linked conductivity, temperature, and depth data loggers on adult males, and six satellite-linked depth data loggers and four satellite transmitters on adult females from St. Paul Island (Bering Sea, Alaska, USA) in October 2009. Males and females migrated to different regions of the North Pacific Ocean: males wintered in the Bering Sea and northern North Pacific Ocean, while females migrated to the Gulf of Alaska and California Current. Horizontal and vertical movement behaviors of both sexes were influenced by wind speed, season, light (sun and moon), and the ecosystem they occupied, although the expression of the behaviors differed between sexes. Male dive depths were aligned with the depth of the mixed layer during daylight periods and we suspect this was the case for females upon their arrival to the California Current. We suggest that females, because of their smaller size and physiological limitations, must avoid severe winters typical of the northern North Pacific Ocean and Bering Sea and migrate long distances to areas of more benign environmental conditions and where prey is shallower and more accessible. In contrast, males can better tolerate often extreme winter ocean conditions and exploit prey at depth because of their greater size and physiological capabilities. We believe these contrasting winter behaviors 1) are a consequence of evolutionary selection for large size in males, important to the acquisition and defense of territories against rivals during the breeding season, and 2) ease environmental

  9. The sun, moon, wind, and biological imperative-shaping contrasting wintertime migration and foraging strategies of adult male and female northern fur seals (Callorhinus ursinus).

    PubMed

    Sterling, Jeremy T; Springer, Alan M; Iverson, Sara J; Johnson, Shawn P; Pelland, Noel A; Johnson, Devin S; Lea, Mary-Anne; Bond, Nicholas A

    2014-01-01

    Adult male and female northern fur seals (Callorhinus ursinus) are sexually segregated in different regions of the North Pacific Ocean and Bering Sea during their winter migration. Explanations for this involve interplay between physiology, predator-prey dynamics, and ecosystem characteristics, however possible mechanisms lack empirical support. To investigate factors influencing the winter ecology of both sexes, we deployed five satellite-linked conductivity, temperature, and depth data loggers on adult males, and six satellite-linked depth data loggers and four satellite transmitters on adult females from St. Paul Island (Bering Sea, Alaska, USA) in October 2009. Males and females migrated to different regions of the North Pacific Ocean: males wintered in the Bering Sea and northern North Pacific Ocean, while females migrated to the Gulf of Alaska and California Current. Horizontal and vertical movement behaviors of both sexes were influenced by wind speed, season, light (sun and moon), and the ecosystem they occupied, although the expression of the behaviors differed between sexes. Male dive depths were aligned with the depth of the mixed layer during daylight periods and we suspect this was the case for females upon their arrival to the California Current. We suggest that females, because of their smaller size and physiological limitations, must avoid severe winters typical of the northern North Pacific Ocean and Bering Sea and migrate long distances to areas of more benign environmental conditions and where prey is shallower and more accessible. In contrast, males can better tolerate often extreme winter ocean conditions and exploit prey at depth because of their greater size and physiological capabilities. We believe these contrasting winter behaviors 1) are a consequence of evolutionary selection for large size in males, important to the acquisition and defense of territories against rivals during the breeding season, and 2) ease environmental

  10. [A rare case of diencephalic cachexia in an adult female with cranio-pharyngioma].

    PubMed

    Klochkova, I S; Astaf'eva, L I; Konovalov, A N; Kadashev, B A; Kalinin, P L; Sharipov, O I; Kutin, M A; Sidneva, Yu G; Shishkina, L V; Pronin, I N

    Diencephalic cachexia (DС) is progressive weight loss despite a normal caloric intake and a satisfactory state of health, which is caused by hypothalamic lesions. This is a rare (about 100 cases were reported) and potentially fatal disorder of unknown pathogenesis. At present, there is no effective pharmacological therapy for the disorder. Cachexia may regress only if the tumor reduces in size, therefore the timely diagnosis and treatment are of vital importance for the patient. DС is typical of early childhood, and only a few cases have been reported in adults. We present a rare case of DС in a 24-year-old female with papillary craniopharyngioma.

  11. All about FAX: a Female Adult voXel phantom for Monte Carlo calculation in radiation protection dosimetry.

    PubMed

    Kramer, R; Khoury, H J; Vieira, J W; Loureiro, E C M; Lima, V J M; Lima, F R A; Hoff, G

    2004-12-07

    The International Commission on Radiological Protection (ICRP) has created a task group on dose calculations, which, among other objectives, should replace the currently used mathematical MIRD phantoms by voxel phantoms. Voxel phantoms are based on digital images recorded from scanning of real persons by computed tomography or magnetic resonance imaging (MRI). Compared to the mathematical MIRD phantoms, voxel phantoms are true to the natural representations of a human body. Connected to a radiation transport code, voxel phantoms serve as virtual humans for which equivalent dose to organs and tissues from exposure to ionizing radiation can be calculated. The principal database for the construction of the FAX (Female Adult voXel) phantom consisted of 151 CT images recorded from scanning of trunk and head of a female patient, whose body weight and height were close to the corresponding data recommended by the ICRP in Publication 89. All 22 organs and tissues at risk, except for the red bone marrow and the osteogenic cells on the endosteal surface of bone ('bone surface'), have been segmented manually with a technique recently developed at the Departamento de Energia Nuclear of the UFPE in Recife, Brazil. After segmentation the volumes of the organs and tissues have been adjusted to agree with the organ and tissue masses recommended by ICRP for the Reference Adult Female in Publication 89. Comparisons have been made with the organ and tissue masses of the mathematical EVA phantom, as well as with the corresponding data for other female voxel phantoms. The three-dimensional matrix of the segmented images has eventually been connected to the EGS4 Monte Carlo code. Effective dose conversion coefficients have been calculated for exposures to photons, and compared to data determined for the mathematical MIRD-type phantoms, as well as for other voxel phantoms.

  12. Risk Factors and Protective Factors in Relation to Subjective Health among Adult Female Victims of Child Sexual Abuse

    ERIC Educational Resources Information Center

    Jonzon, Eva; Lindblad, Frank

    2006-01-01

    Objective: To investigate the relationships between risk and protective factors and health outcome in a sample of adult females who had been victims of child sexual abuse. Method: Both person- and variable-oriented analyses were applied to questionnaire data from a non-clinical group of women (n=152) reporting sexual abuse during childhood.…

  13. A novel disease affecting the predatory mite Phytoseiulus persimilis (Acari, Phytoseiidae): 1. Symptoms in adult females.

    PubMed

    Schütte, Conny; Kleijn, Prisca W; Dicke, Marcel

    2006-01-01

    Adult female Phytoseiulus persimilis Athias-Henriot (Acari, Phytoseiidae) of one of our laboratory populations showed a lower degree of attraction to herbivore-induced plant volatiles than other laboratory populations. We hypothesized earlier that this consistent change in foraging behavior is a symptom of a disease, as it is a contagious phenomenon. Here we describe more symptoms by comparing mated females of this population (non-responding (NR) population) with mated females of other populations that are strongly attracted to herbivore-induced plant volatiles (responding populations). The most apparent characteristic of the NR population was the presence of numerous dorso-ventrally flattened females (76% of all females). These females had a normal size after mating but shrank during adulthood. Independent of their age, shrunken females did not reproduce and died a few days after shrinking. In addition to these profound differences in short term performance, females from the NR-population showed behavioral changes, including a lower degree of attraction to herbivore-induced plant volatiles, a higher tendency to leave a prey-patch and a lower predation rate. Moreover, about half of the live females of the NR-population carried birefringent dumbbell-shaped crystals in the legs whereas live females of a responding population carried crystals only in the lumen of the Malpighian tubules and the rectum. The symptom 'crystals in the legs' was correlated with low reproduction. Energy dispersive X-ray diffraction of these crystals revealed that they contain calcium and phosphorus along with carbon and oxygen. Crystals with comparable elemental compositions and the same characteristic concentric layering are well known in insects, where they are thought to play a major role in detoxification of calcium and heavy metals, and in storage of phosphorus. The fraction of predators carrying a white spot in the distal part of the opisthosoma, due to accumulation of excretory

  14. Breeding sex ratios in adult leatherback turtles (Dermochelys coriacea) may compensate for female-biased hatchling sex ratios.

    PubMed

    Stewart, Kelly R; Dutton, Peter H

    2014-01-01

    For vertebrates with temperature-dependent sex determination, primary (or hatchling) sex ratios are often skewed, an issue of particular relevance to concerns over effects of climate change on populations. However, the ratio of breeding males to females, or the operational sex ratio (OSR), is important to understand because it has consequences for population demographics and determines the capacity of a species to persist. The OSR also affects mating behaviors and mate choice, depending on the more abundant sex. For sea turtles, hatchling and juvenile sex ratios are generally female-biased, and with warming nesting beach temperatures, there is concern that populations may become feminized. Our purpose was to evaluate the breeding sex ratio for leatherback turtles at a nesting beach in St. Croix, USVI. In 2010, we sampled nesting females and later sampled their hatchlings as they emerged from nests. Total genomic DNA was extracted and all individuals were genotyped using 6 polymorphic microsatellite markers. We genotyped 662 hatchlings from 58 females, matching 55 females conclusively to their nests. Of the 55, 42 females mated with one male each, 9 mated with 2 males each and 4 mated with at least 3 males each, for a multiple paternity rate of 23.6%. Using GERUD1.0, we reconstructed parental genotypes, identifying 47 different males and 46 females for an estimated breeding sex ratio of 1.02 males for every female. Thus we demonstrate that there are as many actively breeding males as females in this population. Concerns about female-biased adult sex ratios may be premature, and mate choice or competition may play more of a role in sea turtle reproduction than previously thought. We recommend monitoring breeding sex ratios in the future to allow the integration of this demographic parameter in population models.

  15. Breeding Sex Ratios in Adult Leatherback Turtles (Dermochelys coriacea) May Compensate for Female-Biased Hatchling Sex Ratios

    PubMed Central

    Stewart, Kelly R.; Dutton, Peter H.

    2014-01-01

    For vertebrates with temperature-dependent sex determination, primary (or hatchling) sex ratios are often skewed, an issue of particular relevance to concerns over effects of climate change on populations. However, the ratio of breeding males to females, or the operational sex ratio (OSR), is important to understand because it has consequences for population demographics and determines the capacity of a species to persist. The OSR also affects mating behaviors and mate choice, depending on the more abundant sex. For sea turtles, hatchling and juvenile sex ratios are generally female-biased, and with warming nesting beach temperatures, there is concern that populations may become feminized. Our purpose was to evaluate the breeding sex ratio for leatherback turtles at a nesting beach in St. Croix, USVI. In 2010, we sampled nesting females and later sampled their hatchlings as they emerged from nests. Total genomic DNA was extracted and all individuals were genotyped using 6 polymorphic microsatellite markers. We genotyped 662 hatchlings from 58 females, matching 55 females conclusively to their nests. Of the 55, 42 females mated with one male each, 9 mated with 2 males each and 4 mated with at least 3 males each, for a multiple paternity rate of 23.6%. Using GERUD1.0, we reconstructed parental genotypes, identifying 47 different males and 46 females for an estimated breeding sex ratio of 1.02 males for every female. Thus we demonstrate that there are as many actively breeding males as females in this population. Concerns about female-biased adult sex ratios may be premature, and mate choice or competition may play more of a role in sea turtle reproduction than previously thought. We recommend monitoring breeding sex ratios in the future to allow the integration of this demographic parameter in population models. PMID:24505403

  16. Females Lead Population Collapse of the Endangered Hawaii Creeper

    PubMed Central

    Freed, Leonard A.; Cann, Rebecca L.

    2013-01-01

    Population collapses result from drastic environmental changes, but the sexes may differ in vulnerability. Collapse of the endangered Hawaii creeper (Oreomystis mana) at Hakalau Forest National Wildlife Refuge resulted from food limitation associated with increased numbers of an introduced bird (Japanese white-eye, Zosterops japonicus), which competes with the creeper for food. Both creeper sexes had stunted bill growth and the greatest change in molt of native species in the community. With a surge in numbers of white-eyes, a recent cohort of adult females had very low survival after breeding, while adult males from the same cohort, and older females and males, continued to have high survival. Lower female survival resulted in a significantly more male-biased adult sex ratio. Recent low female survival was based on a great cost of reproduction, indicated by molt-breeding overlap that was previously avoided, and lower fat during the lengthy fledgling period. The difference in female survival between cohorts was associated with stunted bills from being reared in and then breeding in an increasingly poor food environment. Trend analysis of survey data indicate that the bird is declining throughout the refuge, with males being 72–80% of adults left six years after the white-eye increased. Competition over time was consistent with that previously documented over space on the Island of Hawaii. Adaptive management to recover the bird in this protected area needs to focus on improving both adult female survival and the adult sex ratio. PMID:23861831

  17. Females lead population collapse of the endangered Hawaii creeper.

    PubMed

    Freed, Leonard A; Cann, Rebecca L

    2013-01-01

    Population collapses result from drastic environmental changes, but the sexes may differ in vulnerability. Collapse of the endangered Hawaii creeper (Oreomystis mana) at Hakalau Forest National Wildlife Refuge resulted from food limitation associated with increased numbers of an introduced bird (Japanese white-eye, Zosterops japonicus), which competes with the creeper for food. Both creeper sexes had stunted bill growth and the greatest change in molt of native species in the community. With a surge in numbers of white-eyes, a recent cohort of adult females had very low survival after breeding, while adult males from the same cohort, and older females and males, continued to have high survival. Lower female survival resulted in a significantly more male-biased adult sex ratio. Recent low female survival was based on a great cost of reproduction, indicated by molt-breeding overlap that was previously avoided, and lower fat during the lengthy fledgling period. The difference in female survival between cohorts was associated with stunted bills from being reared in and then breeding in an increasingly poor food environment. Trend analysis of survey data indicate that the bird is declining throughout the refuge, with males being 72-80% of adults left six years after the white-eye increased. Competition over time was consistent with that previously documented over space on the Island of Hawaii. Adaptive management to recover the bird in this protected area needs to focus on improving both adult female survival and the adult sex ratio.

  18. Responses of Four Adolescent Females to Adolescent Fiction with Strong Female Characters.

    ERIC Educational Resources Information Center

    Carico, Kathleen M.

    A study examined the effects of a reader response approach to literature in which literature is viewed as a medium for exploration and the effects of such an approach on a group of young women. Subjects of the study were four female middle school students, with the adult female researcher as participant observer. Books chosen for…

  19. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

    PubMed Central

    Bimber, Benjamin N.; Reed, Jason S.; Uebelhoer, Luke S.; Bhusari, Amruta; Hammond, Katherine B.; Klug, Alex; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus; Sacha, Jonah B.

    2016-01-01

    Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago. Despite the ability of Rhesus CMV (RhCMV) laboratory strain 68–1 to replicate efficiently in MCM fibroblasts and potently inhibit antigen presentation to MCM T cells in vitro, RhCMV 68–1 failed to productively infect MCM in vivo, even in the absence of host CD8+ T and NK cells. In contrast, RhCMV clone 68–1.2, genetically repaired to express the homologues of the HCMV anti-apoptosis gene UL36 and epithelial cell tropism genes UL128 and UL130 absent in 68–1, efficiently infected MCM as evidenced by the induction of transgene-specific T cells and virus shedding. Recombinant variants of RhCMV 68–1 and 68–1.2 revealed that expression of either UL36 or UL128 together with UL130 enabled productive MCM infection, indicating that multiple layers of cross-species restriction operate even between closely related hosts. Cumulatively, these results implicate cell tropism and evasion of apoptosis as critical determinants of CMV transmission across primate species barriers, and extend the macaque model of human CMV infection and immunology to MCM, a nonhuman primate species with uniquely simplified host immunogenetics. PMID:27829026

  20. Older maternal age is associated with depression, anxiety, and stress symptoms in young adult female offspring.

    PubMed

    Tearne, Jessica E; Robinson, Monique; Jacoby, Peter; Allen, Karina L; Cunningham, Nadia K; Li, Jianghong; McLean, Neil J

    2016-01-01

    The evidence regarding older parental age and incidence of mood disorder symptoms in offspring is limited, and that which exists is mixed. We sought to clarify these relationships by using data from the Western Australian Pregnancy Cohort (Raine) Study. The Raine Study provided comprehensive data from 2,900 pregnancies, resulting in 2,868 live born children. A total of 1,220 participants completed the short form of the Depression Anxiety Stress Scale (DASS-21) at the 20-year cohort follow-up. We used negative binomial regression analyses with log link and with adjustment for known perinatal risk factors to examine the extent to which maternal and paternal age at childbirth predicted continuous DASS-21 index scores. In the final multivariate models, a maternal age of 30-34 years was associated with significant increases in stress DASS-21 scores in female offspring relative to female offspring of 25- to 29-year-old mothers. A maternal age of 35 years and over was associated with increased scores on all DASS-21 scales in female offspring. Our results indicate that older maternal age is associated with depression, anxiety, and stress symptoms in young adult females. Further research into the mechanisms underpinning this relationship is needed. (c) 2016 APA, all rights reserved.

  1. A Case Study on the Impacts of Connective Technology on Self-Efficacy and Self-Regulated Learning of Female Adult Students Managing Work-Life Balance

    ERIC Educational Resources Information Center

    Sheetz, Tracey L.

    2014-01-01

    Adults frequently define their lives as "hectic" and "overextended;" yet, many make the decision to return to school and add the role of student into their busy lives. This research study explored and explained the impact of connective technology on self-efficacy and self-regulated learning of female adult students balancing…

  2. Photo-anthropometric study on face among Garo adult females of Bangladesh.

    PubMed

    Akhter, Z; Banu, M L A; Alam, M M; Hossain, S; Nazneen, M

    2013-08-01

    Facial anthropometry has well-known implications in health-related fields. Measurement of human face is used in identification of person in Forensic medicine, Plastic surgery, Orthodontics, Archeology, Hair-style design and examination of the differences between races and ethnicities. Facial anthropometry provides an indication of the variations in facial shape in a specified population. Bangladesh harbours many cultures and people of different races because of the colonial rules of the past regimes. Standards based on ethnic or racial data are desirable because these standards reflect the potentially different patterns of craniofacial growth resulting from racial, ethnic and sexual differences. In the above context, the present study was attempted to establish ethnic specific anthropometric data for the Christian Garo adult females of Bangladesh. The study was an observational, cross-sectional and primarily descriptive in nature with some analytical components and it was carried out with a total number of 100 Christian Garo adult females aged between 25-45 years. Three vertical facial dimensions such as facial height from 'trichion' to 'gnathion', nasal length and total vermilion height were measured by photographic method. Though these measurements were taken by photographic method but they were converted into actual size using one of the physically measured variables between two angles of the mouth (chilion to chilion). The data were then statistically analyzed by computation to find out its normatic value. The study also observed the possible 'correlation' between the facial height from 'trichion' to 'gnathion' with nasal length and total vermilion height. Multiplication factors were estimated for estimating facial height from nasal length and total vermilion height. Comparison were made between 'estimated' values with the 'measured' values by using't' test. The mean (+/- SD) of nasal length and total vermilion height were 4.53 +/- 0.36 cm and 1.63 +/- 0.23 cm

  3. Female Adults with Patellofemoral Pain Are Characterized by Widespread Hyperalgesia, Which Is Not Affected Immediately by Patellofemoral Joint Loading.

    PubMed

    Pazzinatto, Marcella Ferraz; de Oliveira Silva, Danilo; Barton, Christian; Rathleff, Michael Skovdal; Briani, Ronaldo Valdir; de Azevedo, Fábio Mícolis

    2016-10-01

    Compare pressure pain thresholds (PPTs) at the knee and a site remote to the knee in female adults with patellofemoral pain (PFP) to pain-free controls before and after a patellofemoral joint (PFJ) loading protocol designed to aggravate symptoms. Cross-sectional study SETTING: Participants were recruited via advertisements in fitness centers, public places for physical activity and universities. Thirty-eight females with patellofemoral pain, and 33 female pain-free controls. All participant performed a novel PFJ loading protocol involving stair negotiation with an extra load equivalent 35% of body mass. PPTs and current knee pain (measured on a visual analogue scale) was assessed before and after the loading protocol. PPTs were measured at four sites around the knee and one remote site on the upper contralateral limb. Females with PFP demonstrated significantly lower PPTs locally and remote to the knee, both before and after the PFJ loading protocol when compared to control group. Following the loading protocol, PPTs at knee were significantly reduced by 0.54 kgf (95%CI = 0.33; 0.74) for quadriceps tendon, 0.38 kgf (95%CI = 0.14; 0.63) for medial patella, and 0.44 kgf (95%CI = 0.18; 0.69) for lateral patella. No significant change in PPT remote to the knee was observed - 0.10 kgf (95%CI = -0.04; 0.24). Female adults with PFP have local and widespread hyperalgesia compared to pain free controls. A novel loading protocol designed to aggravate symptoms, lowers the PPTs locally at the knee but has no effect on PPT on the upper contralateral limb. This suggests widespread hyperalgesia is not affected by acute symptom aggravation. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles.

    PubMed

    Barrett, C E; Arambula, S E; Young, L J

    2015-07-21

    Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity and brain oxytocin receptor (OTR) density on adult social attachment in female prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from postnatal day 1-14. Adult subjects were tested on the partner preference (PP) test to assess social attachment and OTR density in the brain was quantified. Neonatal social isolation impaired female PP formation, without affecting OTR density. Accumbal OTR density was, however, positively correlated with the percent of time spent huddling with the partner in neonatally isolated females. Females with high accumbal OTR binding were resilient to neonatal isolation. These results are consistent with the hypothesis that parental nurturing shapes neural systems underlying social relationships by enhancing striatal OTR signaling. Thus, we next determined whether early touch, mimicking parental licking and grooming, stimulates hypothalamic OT neuron activity. Tactile stimulation induced immediate-early gene activity in OT neurons in neonates. Finally, we investigated whether pharmacologically potentiating OT release using a melanocortin 3/4 agonist, melanotan-II (10 mg kg(-1) subcutaneously), would mitigate the social isolation-induced impairments in attachment behavior. Neonatal melanotan-II administration buffered against the effects of early isolation on partner preference formation. Thus, variation in accumbal OTR density and early OT release induced by parental nurturing may moderate susceptibility to early adverse experiences, including neglect.

  5. The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles

    PubMed Central

    Barrett, C E; Arambula, S E; Young, L J

    2015-01-01

    Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity and brain oxytocin receptor (OTR) density on adult social attachment in female prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from postnatal day 1–14. Adult subjects were tested on the partner preference (PP) test to assess social attachment and OTR density in the brain was quantified. Neonatal social isolation impaired female PP formation, without affecting OTR density. Accumbal OTR density was, however, positively correlated with the percent of time spent huddling with the partner in neonatally isolated females. Females with high accumbal OTR binding were resilient to neonatal isolation. These results are consistent with the hypothesis that parental nurturing shapes neural systems underlying social relationships by enhancing striatal OTR signaling. Thus, we next determined whether early touch, mimicking parental licking and grooming, stimulates hypothalamic OT neuron activity. Tactile stimulation induced immediate-early gene activity in OT neurons in neonates. Finally, we investigated whether pharmacologically potentiating OT release using a melanocortin 3/4 agonist, melanotan-II (10 mg kg−1 subcutaneously), would mitigate the social isolation-induced impairments in attachment behavior. Neonatal melanotan-II administration buffered against the effects of early isolation on partner preference formation. Thus, variation in accumbal OTR density and early OT release induced by parental nurturing may moderate susceptibility to early adverse experiences, including neglect. PMID:26196439

  6. Azelaic acid in the treatment of acne in adult females: case reports.

    PubMed

    Vargas-Diez, E; Hofmann, M A; Bravo, B; Malgazhdarova, G; Katkhanova, O A; Yutskovskaya, Y

    2014-01-01

    Acne, one of the most common skin problems in dermatological practice, is a condition that affects not only adolescents but also adults. While approximately 80% of cases occurring in adulthood are persistent from teenage years, around 20% are described as 'late-onset' disease, appearing for the first time in adulthood. The disease can be triggered by hormonal changes (including a change from one contraceptive to another), or it can be induced by certain nonhormonal medications, emotional stress, and various underlying diseases such as polycystic ovary syndrome. In many cases acne becomes a chronic skin condition with undulating activity, including improvement and relapse phases, and is often experienced as a major psychological burden. It is, therefore, even more important to provide an effective as well as a safe and tolerable treatment. The spectrum of topical acne treatments has expanded substantially in recent years and various topical medications are available, ranging from azelaic acid, antibiotics, retinoids and benzoyl peroxide to several fixed combinations of these active compounds. The following case collection illustrates how 15% azelaic acid gel, as a well-established monotherapy, can be successfully employed to treat mild-to-moderate forms of adult female acne. © 2013 S. Karger AG, Basel.

  7. Effects of long-term construction noise on health of adult female Wistar rats.

    PubMed

    Zymantiene, J; Zelvyte, R; Pampariene, I; Aniuliene, A; Juodziukyniene, N; Kantautaite, J; Oberauskas, V

    2017-03-28

    The aim of this study was to investigate the influence of long-term building construction noise from refurbishment, which including vibration, on some physiological parameters and histopathological changes of organs of Wistar rats. Twenty 12 month old female rats were divided into two groups: rats group I (n = 10) were exposed to long-term construction noise and rats group II (n = 10) were kept under normal noise level. Study results revealed that long-term construction noise from building refurbishment has an influence on body weight, haematological and some serum biochemical parameters affects caecal microbiota, and causes histopathological changes in the organs of adult female Wistar rats. It was noticed that rats in group I exihibited significantly higher mean values for total protein, albumin and lower values for glucose, AST, ALT, blood urea nitrogen, haematological and caecal microbiota parameters than rats in group II. The most common pathologies were determined in the kidney, liver and lungs. Other observed pathologies were lymphadenopathy, catarrhal inflammation of the intestines, spleen hyperplasia and mammary gland adenofibroma. Single cases were subcutaneous fibroma in the thoracic region, abortus with uterine inflammation and thymus hyperplasia with formation of cysts were found.

  8. Angiostrongylus cantonensis: identification and characterization of microRNAs in male and female adults.

    PubMed

    Chen, Mu-Xin; Ai, Lin; Xu, Min-Jun; Zhang, Ren-Li; Chen, Shao-Hong; Zhang, Yong-Nian; Guo, Jian; Cai, Yu-Chun; Tian, Li-Guang; Zhang, Ling-Ling; Zhu, Xing-Quan; Chen, Jia-Xu

    2011-06-01

    Angiostrongylus cantonensis causes eosinophilic meningitis and eosinophilic pleocytosis in humans and is of significant socio-economic importance globally. microRNAs (miRNAs) are endogenous small non-coding RNAs that play crucial roles in gene expression regulation, cellular function and defense, homeostasis and pathogenesis. They have been identified in a diverse range of organisms. The objective of this study was to determine and characterize miRNAs of female and male adults of A. cantonensis by Solexa deep sequencing. A total of 8,861,260 and 10,957,957 high quality reads with 20 and 23 conserved miRNAs were obtained in females and males, respectively. No new miRNA sequence was found. Nucleotide bias analysis showed that uracil was the prominent nucleotide, particularly at positions of 1, 10, 14, 17 and 22, approximately at the beginning, middle and the end of the conserved miRNAs. To our knowledge, this is the first report of miRNA profiles in A. cantonensis, which may represent a new platform for studying regulation of genes and their networks in A. cantonensis. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Anabolic effects of chrysin on the ventral male prostate and female prostate of adult gerbils (Meriones unguiculatus).

    PubMed

    Campos, Mônica S; Ribeiro, Naiara C S; de Lima, Rodrigo F; Santos, Mariana B; Vilamaior, Patrícia S L; Regasini, Luis O; Biancardi, Manoel F; Taboga, Sebastião R; Santos, Fernanda C A

    2018-03-07

    Chrysin is a bioflavonoid found in fruits, flowers, tea, honey and wine, which has antioxidant, anti-inflammatory, antiallergic and anticarcinogenic properties. This flavone has also been considered as beneficial for reproduction due its testosterone-boosting potential. Thus, the aim of this study was to evaluate the effects of chrysin on the prostate and gonads of male and female adult gerbils. In addition, a comparative analysis of the effects of testosterone on these same organs was conducted. Ninety-day-old male and female gerbils were treated with chrysin (50mgkg-1day-1) or testosterone cypionate (1mgkg-1week-1) for 21 days. The ventral male prostate and female prostate were dissected out for morphological, morphometric-stereological and ultrastructural assays. Testes and ovaries were submitted to morphological and morphometric---stereological analyses. Chrysin treatment caused epithelial hyperplasia and stromal remodelling of the ventral male and female prostate. Ultrastructurally, male and female prostatic epithelial cells in the chrysin group presented marked development of the organelles involved in the biosynthetic-secretory pathway, whereas cellular toxicity was observed only in female glands. Chrysin preserved normal testicular morphology and increased the number of growing ovarian follicles. Comparatively, testosterone treatment was detrimental to the prostate and gonads, since foci of prostatic intraepithelial neoplasia and gonadal degeneration were observed in both sexes. Thus, under the experimental conditions of this study, chrysin was better tolerated than testosterone in the prostate and gonads.

  10. Enduring influences of peripubertal/adolescent stressors on behavioral response to estradiol and progesterone in adult female mice.

    PubMed

    Laroche, Julie; Gasbarro, Lauren; Herman, James P; Blaustein, Jeffrey D

    2009-08-01

    Exposure to stressors during particular stages of development leads to acute and long-term physiological and behavioral changes. We have reported that shipping mice during the peripubertal/adolescent period results in decreased induction of feminine sexual behavior by estradiol and progesterone in adult female mice. To study further the factors involved in this decreased behavioral response, female mice were exposed to a variety of experimental stressors when 6 wk old. Effects of peripubertal/adolescent exposure to these stressors on acute plasma corticosterone levels and changes in body weight and adult behavioral response to estradiol and progesterone were assessed. Although restraint for three daily 3-h periods, 36-h food deprivation, or a multiple stressor regimen acutely increased plasma corticosterone levels and reduced body weight, only exposure to particular doses of the bacterial endotoxin lipopolysaccharide (LPS; 1-1.5 mg/kg body weight, doses that induced moderate levels of sickness behavior in these studies) resulted in reduced behavioral response to estradiol and progesterone in adulthood. Like the effects of shipping, the effects of LPS on adult feminine sexual behavior appear most robust when injected at 6 wk old and are limited to exposure during a vulnerable period at approximately 4-6 wk of age. Therefore, an immune stressor during the peripubertal/adolescent period, but not restraint, food restriction, or a combined stressor, has an enduring influence on behavioral response to estradiol and progesterone. This demonstrates that the decreased response to estradiol and progesterone is not a general response to all stressors during this developmental stage.

  11. Comparison of the vaginal environment in rhesus and cynomolgus macaques pre- and post-lactobacillus colonization.

    PubMed

    Daggett, Gregory J; Zhao, Chunxia; Connor-Stroud, Fawn; Oviedo-Moreno, Patricia; Moon, Hojin; Cho, Michael W; Moench, Thomas; Anderson, Deborah J; Villinger, Francois

    2017-10-01

    Rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (HIV) prevention strategies. However, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this study. We tested the vaginal environment of rhesus and cynomolgus macaques longitudinally to characterize the normal microflora based on Nugent scores and pH. This evaluation was extended after colonization of the vaginal space with Lactobacilli in an effort to recreate NHP models representing the healthy human vaginal environment. Nugent scores and pH differed significantly between species, although data from both species were suggestive of stable bacterial vaginosis. Colonization with Lactobacilli was successful in both species leading to lower Nugent score and pH, although rhesus macaques appeared better able to sustain Lactobacillus spp over time. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. The role of adolescent behaviors in the female-male disparity in obesity incidence in US black and white young adults.

    PubMed

    Robinson, Whitney R; Stevens, June; Kaufman, Jay S; Gordon-Larsen, Penny

    2010-07-01

    In the United States, black women are at much greater risk for obesity than black men. We explored whether adolescent behaviors (family dinners, hours of television, playing sports with mother, playing sports with father, bouts of physical activity) were associated with gender disparity in 6-year obesity incidence in young adulthood. We used data from the nationally representative National Longitudinal Study of Adolescent Health to examine adolescent behaviors in nonimmigrant black (n = 1,503) and white (n = 4,452) youths in 1994-95 (aged 11-19 years) and 1995-96 (aged 12-20). We assessed gender disparity in obesity incidence (female incidence minus male incidence) during young adulthood (2001-02; aged 18-26). Standardized gender disparities were calculated using race- and gender-stratified, covariate-adjusted logistic regression models in which males and females were set to the same distributions of adolescent behaviors. In adolescence, black females reported less leisure-time physical activity and lower likelihood of playing sports with either parent compared with black males. Setting adolescent behaviors equal for black males and females did not reduce the estimated gender disparity in obesity incidence (nonstandardized: 9.8 percentage points (95% confidence interval (CI): 4.5, 15.1); fully standardized: 10.2 percentage points (5.2, 15.2)). There was little gender disparity in whites before or after adjustments. To our knowledge, this is the first study to examine to what extent behavioral differences during adolescence might account for gender disparity in obesity incidence in black young adults. Male-female differences in these adolescent behaviors did not appear to underlie the gender gap in young adult obesity.

  13. A Diversified Recruitment Approach Incorporating Social Media Leads to Research Participation Among Young Adult-Aged Female Cancer Survivors.

    PubMed

    Gorman, Jessica R; Roberts, Samantha C; Dominick, Sally A; Malcarne, Vanessa L; Dietz, Andrew C; Su, H Irene

    2014-06-01

    Purpose: Cancer survivors in their adolescent and young adult (AYA) years are an understudied population, possibly in part because of the high effort required to recruit them into research studies. The aim of this paper is to describe the specific recruitment strategies used in four studies recruiting AYA-aged female cancer survivors and to identify the highest yielding approaches. We also discuss challenges and recommendations. Methods: We recruited AYA-aged female cancer survivors for two studies conducted locally and two conducted nationally. Recruitment strategies included outreach and referral via: healthcare providers and clinics; social media and the internet; community and word of mouth; and a national fertility information hotline. We calculated the yield of each recruitment approach for the local and national studies by comparing the number that participated to the number of potential participants. Results: We recruited a total of 534 participants into four research studies. Seventy-one percent were diagnosed as young adults and 61% were within 3 years of their cancer diagnosis. The highest-yielding local recruitment strategy was healthcare provider and clinic referral. Nationally, social media and internet outreach yielded the highest rate of participation. Overall, internet-based recruitment resulted in the highest number and yield of participants. Conclusion: Our results suggest that outreach through social media and the internet are effective approaches to recruiting AYA-aged female cancer survivors. Forging collaborative relationships with survivor advocacy groups' members and healthcare providers also proved beneficial.

  14. A Diversified Recruitment Approach Incorporating Social Media Leads to Research Participation Among Young Adult-Aged Female Cancer Survivors

    PubMed Central

    Gorman, Jessica R.; Roberts, Samantha C.; Dominick, Sally A.; Malcarne, Vanessa L.; Dietz, Andrew C.

    2014-01-01

    Purpose: Cancer survivors in their adolescent and young adult (AYA) years are an understudied population, possibly in part because of the high effort required to recruit them into research studies. The aim of this paper is to describe the specific recruitment strategies used in four studies recruiting AYA-aged female cancer survivors and to identify the highest yielding approaches. We also discuss challenges and recommendations. Methods: We recruited AYA-aged female cancer survivors for two studies conducted locally and two conducted nationally. Recruitment strategies included outreach and referral via: healthcare providers and clinics; social media and the internet; community and word of mouth; and a national fertility information hotline. We calculated the yield of each recruitment approach for the local and national studies by comparing the number that participated to the number of potential participants. Results: We recruited a total of 534 participants into four research studies. Seventy-one percent were diagnosed as young adults and 61% were within 3 years of their cancer diagnosis. The highest-yielding local recruitment strategy was healthcare provider and clinic referral. Nationally, social media and internet outreach yielded the highest rate of participation. Overall, internet-based recruitment resulted in the highest number and yield of participants. Conclusion: Our results suggest that outreach through social media and the internet are effective approaches to recruiting AYA-aged female cancer survivors. Forging collaborative relationships with survivor advocacy groups' members and healthcare providers also proved beneficial. PMID:24940529

  15. A simple orchidometric method for the preliminary assessment of maturity status in male cynomolgus monkeys (Macaca fascicularis) used for nonclinical safety studies.

    PubMed

    Ku, Warren W; Pagliusi, Frank; Foley, George; Roesler, Alfred; Zimmerman, Thomas

    2010-01-01

    The identification and use of mature male non-human primates in nonclinical toxicology studies could be important for evaluating candidate drugs for which the profile of toxicity may differ depending on sexual maturity. This investigation sought to establish operational criteria to complement the current standard of histological evaluation for defining sexual maturity in male cynomolgus monkeys (Macaca fascicularis) used for toxicology studies, and to identify a practical non-invasive measure to select mature males for study. Retrospectively, the relationships between body weight, testicular weight and testis histology were established in control males (n=126) used in previous toxicology studies. Prospectively, testicular volumes were measured in-life by orchidometry using comparative scrotal palpation (n=23 males used for study), then compared to testicular weights measured at necropsy. Consistent with previous literature, a weak relationship was observed between body weight and testicular weight. There was, however, a very good relationship between testicular weight and histological maturation level, which was based upon microscopic examination of testes, epididymides and prostates. Orchidometric measurement of testicular volume was found to be a reasonable predictor of testicular weight and served to rapidly select sexually mature males for study, and a total testicular volume (left and right combined) of >20 ml correlated with the histological appearance of maturity. Based upon this preliminary exploratory study, the initial simple measurement of testicular volume by orchidometry may provide a non-invasive alternative approach for assessing the sexual maturity of male cynomolgus monkeys in research colonies or during toxicology studies that will require more thorough validation. Copyright 2009 Elsevier Inc. All rights reserved.

  16. Effects of permethrin and amitraz on gas exchange and water loss in unfed adult females of Amblyomma americanum (Acari: Ixodidae)

    USDA-ARS?s Scientific Manuscript database

    Effects of permethrin and amitraz on metabolism of the lone star tick, Amblyomma americanum, were examined using a flow-through carbon dioxide (CO2) and water vapor analyzer. Untreated adult female ticks exhibited a distinct discontinuous gas exchange pattern (DGEP) with no measurable water loss. Si...

  17. Weight-Related Correlates of Psychological Dysregulation in Adolescent and Young Adult (AYA) Females with Severe Obesity

    PubMed Central

    Gowey, Marissa A.; Reiter-Purtill, Jennifer; Becnel, Jennifer; Peugh, James; Mitchell, James E.; Zeller, Meg H.

    2016-01-01

    Objective Severe obesity is the fastest growing pediatric subgroup of excess weight levels. Psychological dysregulation (i.e., impairments in regulating cognitive, emotional, and/or behavioral processes) has been associated with obesity and poorer weight loss outcomes. The present study explored associations of dysregulation with weight-related variables among adolescent and young adult (AYA) females with severe obesity. Methods Fifty-four AYA females with severe obesity (MBMI=48.71 kg/m2; Mage=18.29, R=15–21 years; 59.3% White) completed self-report measures of psychological dysregulation and weight-related constructs including meal patterns, problematic eating behaviors, and body and weight dissatisfaction, as non-surgical comparison participants in a multi-site study of adolescent bariatric surgery outcomes. Pearson and bivariate correlations were conducted and stratified by age group to analyze associations between dysregulation subscales (affective, behavioral, cognitive) and weight-related variables. Results Breakfast was the most frequently skipped meal (consumed 3–4 times/week). Eating out was common (4–5 times/week) and mostly occurred at fast-food restaurants. Evening hyperphagia (61.11%) and eating in the absence of hunger (37.04%) were commonly endorsed, while unplanned eating (29.63%), a sense of loss of control over eating (22.22%), eating beyond satiety (22.22%), night eating (12.96%), and binge eating (11.11%) were less common. Almost half of the sample endorsed extreme weight dissatisfaction. Dysregulation was associated with most weight-related attitudes and behaviors of interest in young adults but select patterns emerged for adolescents. Conclusions Higher levels of psychological dysregulation are associated with greater BMI, problematic eating patterns and behaviors, and body dissatisfaction in AYA females with severe obesity. These findings have implications for developing novel intervention strategies for severe obesity in AYAs that may

  18. [Comparative study of the long-term behavioral effects of noopept and piracetam in adult male rats and female rats in postnatal period].

    PubMed

    Voronina, T A; Guzevatykh, L S; Trofimov, S S

    2005-01-01

    Adult male and female rats were treated with the peptide nootrope drug noopept (daily dose, 0.1 mg/kg) and piracetam (200 mg/kg). In the period from 8th to 20th day, both drugs (cognitive enhancers) suppressed the horizontal and vertical activity and the anxiety in test animals as compared to the control group treated with 0.9 % aqueous NaCl solution. Early postnatal injections of the nootropes influenced neither the morphology development nor the behavior of adult female rats in the plus maze, extrapolational escape, passive avoidance, and pain sensitivity threshold tests. Animals in the "intact" group (having received neither drugs not physiological solution, that is, developing in a poor sensor environment), showed less pronounced habituation in the open field test as compared to the control and drug treated groups.

  19. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shen, Lang; Liu, Zhongfen; Gong, Jun

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growthmore » factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure

  20. Sex differences in stress-induced social withdrawal: independence from adult gonadal hormones and inhibition of female phenotype by corncob bedding.

    PubMed

    Trainor, Brian C; Takahashi, Elizabeth Y; Campi, Katharine L; Florez, Stefani A; Greenberg, Gian D; Laman-Maharg, Abigail; Laredo, Sarah A; Orr, Veronica N; Silva, Andrea L; Steinman, Michael Q

    2013-03-01

    There is compelling evidence for important sex differences in behavioral and hormonal responses to psychosocial stress. Here we examined the effects of gonadal hormones on behavioral responses to social defeat stress in monogamous California mice (Peromyscus californicus). Three episodes of social defeat induced social withdrawal in intact females but not males. Gonadectomy blocked corticosterone responses to defeat in females and sensitized male corticosterone responses. However, gonadectomy had no effects on social interaction behavior, suggesting that social withdrawal is not dependent on gonadal hormones in the adult California mouse. In contrast, defeat reduced exploratory behavior in the open field test for intact but not castrated males. We also examined the effects of social defeat on social interaction behavior when California mice were raised on corncob bedding, which has estrogenic properties. In this dataset of over 300 mice, we observed that social defeat did not induce social withdrawal when females were raised on corncob bedding. This finding suggests that the use of corncob in rodent studies could mask important sex differences in the effects of stress on brain and behavior. Although gonadal hormones do not affect social withdrawal behavior in adults, our data suggest that hormones may act earlier in development to induce a more resilient social phenotype. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Adoption consideration and concerns among young adult female cancer survivors.

    PubMed

    Gorman, Jessica R; Whitcomb, Brian W; Standridge, Daniel; Malcarne, Vanessa L; Romero, Sally A D; Roberts, Samantha A; Su, H Irene

    2017-02-01

    We compared adoption consideration between female young adult cancer survivors and women of the same age in the general US population, hypothesizing that cancer survivors who desired children would report greater interest in adoption than an age-adjusted general population sample who desired children. After age-standardizing the cancer survivor cohort to match the age distribution of the 2006-2010 National Survey for Family Growth (NSFG), we estimated adoption consideration among women age 18-35 years who wanted a (another) child in the two cohorts overall and within age groups. We assessed characteristics and concerns related to adoption consideration among cancer survivors. Among cancer survivors, 81.6 % (95 % CI 75.7-87.6) reported that they would consider adoption compared to 40.3 % (95 % CI 40.3-40.3) of women in the general population. While over 80 % of the cancer survivor sample reported that they would consider adoption, only 15 % of cancer survivors reported no concerns about adoption. The most common concerns were desire for a biological child (48 %), expense (45 %), adoption agency candidacy (41 %), and needing more information (39 %). We observed a twofold higher interest in adoption when comparing the cancer survivor with the general population, suggesting that adoption is a consideration for many young women who have survived cancer. Adoption is an important family-building option for those who want to have a child but are unable to or choose not to have a biological child. However, young adult survivors may need more support to understand and navigate this process.

  2. The Long-Term Effects of Childhood Bullying Experiences on Female Adults as It Relates to Their Perception of Themselves and Their Relationships with Women

    ERIC Educational Resources Information Center

    Barcalow, Julia M.

    2013-01-01

    Childhood bullying is a phenomenon that affects many individuals well beyond their childhood. This study looked specifically at female adults, and how the bullying they experienced in their childhood continues to have long-term effects on them in their adult lives. The purpose of this study was to explore the long-term effects that bullying has on…

  3. Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after long-term immunosuppressive therapy

    PubMed Central

    Guimarães, Juliana Rodrigues; Melgaço, Juliana Gil; Kevorkian, Yohan Britto; Bottino, Fernanda de Oliveira; Vieira, Yasmine Rangel; da Silva, Aline Campos de Azevedo; Pinto, Douglas Pereira; da Fonseca, Laís Bastos; Vilhena, Leandro Schiavo; Uiechi, Edilson; da Silva, Maria Cristina Carlan; Moran, Julio; Marchevsky, Renato Sérgio; Cruz, Oswaldo Gonçalves; Otonel, Rodrigo Alejandro Arellano; Alfieri, Amauri Alcindo; de Oliveira, Jaqueline Mendes; Gaspar, Ana Maria Coimbra; Pinto, Marcelo Alves

    2017-01-01

    Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. Immunosuppression was confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels; persistent RNA viremia and viral faecal shedding; and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi, the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis

  4. Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ryan, Patricia C., E-mail: ryanp@medimmune.com; Sleeman, Matthew A.; Rebelatto, Marlon

    Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters othermore » than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus

  5. Allogeneic lymphocytes persist and traffic in feral MHC-matched mauritian cynomolgus macaques.

    PubMed

    Greene, Justin M; Burwitz, Benjamin J; Blasky, Alex J; Mattila, Teresa L; Hong, Jung Joo; Rakasz, Eva G; Wiseman, Roger W; Hasenkrug, Kim J; Skinner, Pamela J; O'Connor, Shelby L; O'Connor, David H

    2008-06-11

    Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer. Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer. MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naïve animals may define the immune mechanisms responsible for protection and guide future vaccine development.

  6. Pulmonary Embolization of Fat and Bone Marrow in Cynomolgus Macaques (Macaca fascicularis)

    PubMed Central

    Fong, Derek L.; Murnane, Robert D.; Hotchkiss, Charlotte E.; Green, Damian J.; Hukkanen, Renee R.

    2011-01-01

    Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. PMID:21819686

  7. Pulmonary embolization of fat and bone marrow in cynomolgus Macaques (Macaca fascicularis).

    PubMed

    Fong, Derek L; Murnane, Robert D; Hotchkiss, Charlotte E; Green, Damian J; Hukkanen, Renee R

    2011-02-01

    Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma.

  8. Testicular Fibrous Hypoplasia in Cynomolgus Monkeys ( Macaca fascicularis): An Incidental, Congenital Lesion.

    PubMed

    Pereira Bacares, Marcia E; Vemireddi, Vimala; Creasy, Dianne

    2017-06-01

    Testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. A retrospective survey of hematoxylin and eosin-stained testicular sections from 722 purpose-bred Asian and 90 Mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. The incidence of the lesion increased markedly over time. No cases occurred between 1999 and 2004. Between 2005 and 2009, the incidence ranged between 8.1% and 11.0% of the monkeys examined and then rose to 26.1% in 2010 and 30.9% in 2011. Overall, the lesion was identified in 10.94% of Asian monkeys with the highest incidence in animals originating from China and Vietnam; severity ranged from minimal to severe and it occurred unilaterally (38.5%) and bilaterally (61.5%). In Mauritian monkeys, the lesion was predominantly minimal in severity, bilateral in distribution, and affected 6.6% of the animals examined. The lesion occurred regardless of sexual maturation status but when present in mature monkeys was often associated with cystic tubular atrophy of the seminiferous epithelium. Based on the morphological characteristics of the lesion and the unilateral/bilateral distribution, the lesion is considered to be a congenital or developmental abnormality.

  9. Spontaneous Findings in the Eyes of Cynomolgus Monkeys ( Macaca fascicularis) of Mauritian Origin.

    PubMed

    Woicke, Jochen; Haile, Solomon; Mysore, Jagannatha; Peden, W Michael; Lejeune, Typhaine; Sanderson, Thomas; Brodie, Thomas

    2018-04-01

    Spontaneous findings noted in the eyes of Mauritian cynomolgus monkeys are described and descriptions are supplemented with illustrations. Findings observed after extensive histopathologic examinations (20 to 44 sections per eye) from 20 control, 17 treatment-naive stock monkeys, and 2 findings noted in drug-treated monkeys that were considered to be spontaneous are included. Also included are findings from 361 control monkeys of routine toxicity studies performed at our laboratories, for most of which a standard histopathological examination of 1 section per eye was conducted. Common observations in monkeys examined extensively and in historical controls were limited to lymphocytic or mononuclear cell infiltrations of the uvea and/or conjunctiva/sclera and, less commonly observed, melanocytoma of the ciliary body or iris. Findings noted only in monkeys examined extensively consisted of inflammation of the conjunctiva, ora serrata cysts, glial nodules, focal degeneration of the retina, cystoid degeneration of the central retina, ballooning degeneration of the ciliary epithelium, cyst of the ciliary body, and decreased pigmentation of the retinal pigment epithelium. Changes recorded only in historical controls included retinal atrophy and nuclear displacement in the retina. Lesions are discussed and compared with pertinent literature.

  10. Differences in male and female spino-pelvic alignment in asymptomatic young adults: a three-dimensional analysis using upright low-dose digital biplanar X-rays.

    PubMed

    Janssen, Michiel M A; Drevelle, Xavier; Humbert, Ludovic; Skalli, Wafa; Castelein, René M

    2009-11-01

    A three-dimensional analysis of spino-pelvic alignment in 60 asymptomatic young adult males and females. To analyze the differences in sagittal spino-pelvic alignment in a group of asymptomatic young adult males and females and describe gender specific reference values. Several spinal disorders like idiopathic scoliosis and Scheuermann's disease have a well-known sex-related prevalence ratio. As spino-pelvic alignment plays an important role in spinal biomechanics, it is imperative to analyze possible differences between the male and female spino-pelvic alignment. Furthermore, in spinal fusion surgery, normal sagittal balance should be recreated as closely as possible. An innovative biplanar ultra low-dose radiographic technique was used to obtain three-dimensional reconstructions of the spine (T1-L5), sacrum, and pelvis in a freestanding position of 30 asymptomatic young male and 30 young female adults. Values were calculated for thoracic kyphosis (T4-T12), lumbar lordosis (L1-S1), total and regional lumbopelvic lordosis (PRT12, PRL2, PRL4, and PRL5), sagittal plumb line of T1, T4, and T9 (HAT1, HAT4, and HAT9), T1-L5 sagittal spinal inclination, T9 sagittal offset, and pelvic parameters (pelvic tilt, sacral slope, and pelvic incidence). In addition, vertebral inclination in the sagittal plane of each vertebra was measured. Differences in spino-pelvic alignment between the sexes were analyzed. The female spine was more dorsally inclined (11 degrees vs. 8 degrees ; P = 0.003). High thoracic and thoracolumbar vertebrae were more dorsally inclined in women than in men. Thoracic kyphosis, lumbar lordosis, regional lumbopelvic lordosis, sagittal plumb lines, T9 sagittal offset, and pelvic parameters were not statistically different between the sexes. These results indicate that the female spine is definitely different from the male spine. The spine as whole and individual vertebrae in certain regions of the normal spine is more backwardly inclined in females than in

  11. Adolescent cannabinoid exposure attenuates adult female sexual motivation but does not alter adulthood CB1R expression or estrous cyclicity

    PubMed Central

    Chadwick, Benjamin; Saylor, Alicia J.; López, Hassan H.

    2013-01-01

    Adolescence is a developmental period characterized by neuronal remodeling and the maturation of adult emotionality, reproductive behavior and social behavior. We examined whether chronic cannabinoid exposure in adolescent rats alters female sexual motivation, estrous cyclicity, sucrose preference, and CB1R expression in adulthood. Female rats were administered with the synthetic cannabinoid agonist, CP-55,940 (0.4 mg/kg, intraperitoneal), daily during adolescent development (PND 35–45). In a subset of subjects, socio-sexual motivation was investigated in adulthood (PND 75–86) using a runway apparatus. Estrous cyclicity was tracked in adulthood via vaginal cytology and a single-mount test. A two-bottle sucrose preference test was also conducted to determine whether predicted changes in socio-sexual motivation might be linked to alterations in hedonic processing. CB1R expression was examined in two separate subsets of subjects, one sacrificed following drug treatment (PND 46) and one before behavioral testing (PND 74). Drug treatment significantly decreased adult preference for a male conspecific (sexual motivation), as assessed by both Run Time and Proximity Time, but did not affect estrous cyclicity or sucrose preference. CP-55,940 treatment also induced immediate, but transient, decreases in CB1R expression in the ventromedial nucleus of the hypothalamus and amygdala. Drug treatment did not affect CB1R expression in the nucleus accumbens (core or shell) or globus pallidus at either time point. We suggest that the endocannabinoid system may play a role in the maturation of neuroendocrine axes and adult female reproductive behavior, and that chronic exposure to cannabinoids during adolescence disrupts these neurodevelopmental processes. PMID:21777606

  12. Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

    PubMed

    Shiina, Takashi; Yamada, Yukiho; Aarnink, Alice; Suzuki, Shingo; Masuya, Anri; Ito, Sayaka; Ido, Daisuke; Yamanaka, Hisashi; Iwatani, Chizuru; Tsuchiya, Hideaki; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Kulski, Jerzy K; Blancher, Antoine

    2015-10-01

    Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86%) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2%, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

  13. Differential behavioral effects of nicotine in adult male and female rats with a history of prenatal methamphetamine exposure.

    PubMed

    Rorabaugh, Boyd; Seeley, Sarah; Evans, Mary; Marengo, Christina; D'Souza, Manoranjan

    2017-06-09

    The goal of the current study was to assess the effects of prenatal methamphetamine (MA)/saline exposure on nicotine-induced stimulant and aversive effects in both male and female adult rats. The aversive effects of nicotine were assessed using the nicotine-induced conditioned taste aversion model (0.4mg/kg, base), while the stimulant effects of nicotine were measured by assessing changes in spontaneous locomotor activity after subcutaneous administration of different doses of nicotine (0, 0.1 & 0.4mg/kg, base). The aversive effects of nicotine were significantly decreased in male, but not in female rats with a history of prenatal MA exposure compared to respective saline controls. No influence of prenatal MA exposure was observed on nicotine-induced increase in locomotor activity in either male or female rats. In conclusion, males with a history of prenatal MA exposure may be more vulnerable to nicotine addiction due to a decrease in nicotine-induced aversive effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.

    PubMed

    Bale, Laurie K; West, Sally A; Conover, Cheryl A

    2017-08-01

    Pregnancy-associated plasma protein-A (PAPP-A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild-type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP-A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)-inducible Cre recombinase-mediated excision of the floxed PAPP-A (fPAPP-A) gene in mice at 5 months of age. fPAPP-A mice, which were either positive (pos) or negative (neg) for Tam-Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP-A/neg and fPAPP-A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP-A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP-A/pos compared to fPAPP-A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP-A/pos mice were lower than fPAPP-A/neg mice at young adult ages (P = 0.002 for 601-800 days) and higher than fPAPP-A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age-specific mortality indicate that female mice with knockdown of PAPP-A gene expression as adults have an extended healthy life span. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  15. Short-term social memory deficits in adult female mice exposed to tannery effluent and possible mechanism of action.

    PubMed

    Estrela, Fernanda Neves; Rabelo, Letícia Martins; Vaz, Boniek Gontijo; de Oliveira Costa, Denys Ribeiro; Pereira, Igor; de Lima Rodrigues, Aline Sueli; Malafaia, Guilherme

    2017-10-01

    The accumulated organic residues in tannery-plant courtyards are an eating attraction to small rodents; however, the contact of these animals with these residues may change their social behavior. Thus, the aim of the present study is to investigate whether the exposure to tannery effluent (TE) can damage the social recognition memory of female Swiss mice, as well as to assess whether vitamin C supplementation could provide information about how TE constituents can damage these animals' memory. We have observed that resident females exposed to TE (without vitamin supplementation) did not explore the anogenital region, their body or chased intruding females for shorter time or with lower frequency during the retest session of the social recognition test, fact that indicates social recognition memory deficit in these animals. Such finding is reinforced by the confirmation that there was no change in the animals' olfactory function during the buried food test, or locomotor changes in females exposed to the pollutant. Since no behavioral change was observed in the females exposed to TE and treated with vitamin C (before or after the exposure), it is possible saying that these social cognitive impairments seem to be directly related to the imbalance between the cellular production of reactive oxygen species and the counteracting antioxidant mechanisms (oxidative stress) in female mice exposed to the pollutant (without vitamin supplementation). Therefore, the present study evidences that the direct contact with tannery effluent, even for a short period-of-time, may cause short-term social memory deficits in adult female Swiss mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The role of adolescent behaviors in the female-male disparity in obesity incidence in U.S. Black and White young adults

    PubMed Central

    Robinson, Whitney R.; Stevens, June; Kaufman, Jay S.; Gordon-Larsen, Penny

    2009-01-01

    In the United States, Black women are at much greater risk for obesity than Black men. We explored whether adolescent behaviors (family dinners, hours of television, playing sports with mother, playing sports with father, bouts of physical activity) were associated with gender disparity in six-year obesity incidence in young adulthood. We used data from the nationally representative National Longitudinal Study of Adolescent Health to examine adolescent behaviors in non-immigrant Black (n=1503) and White (n=4452) youths in 1994–95 (aged 11–19 years) and 1995–96 (aged 12–20). We assessed gender disparity in obesity incidence (female incidence minus male incidence) during young adulthood (2001–02; aged 18–26). Standardized gender disparities were calculated using race- and gender-stratified, covariate-adjusted logistic regression models in which males and females were set to the same distributions of adolescent behaviors. In adolescence, Black females reported less leisure-time physical activity and lower likelihood of playing sports with either parent than Black males. Setting adolescent behaviors equal for Black males and females did not reduce the estimated gender disparity in obesity incidence (non-standardized: 9.8 percentage points [95% CI: 4.5, 15.1]; fully-standardized: 10.2 percentage points [5.2, 15.2]). There was little gender disparity in Whites before or after adjustments. To our knowledge, this is the first study to examine to what extent behavioral differences during adolescence might account for gender disparity in obesity incidence in Black young adults. Male-female differences in these adolescent behaviors did not appear to underlie the gender gap in young adult obesity. PMID:19875993

  17. Reversing song behavior phenotype: testosterone driven induction of singing and measures of song quality in adult male and female canaries (Serinus canaria)

    PubMed Central

    Madison, Farrah N.; Rouse, Melvin L.; Balthazart, Jacques; Ball, Gregory F

    2014-01-01

    In songbirds, such as canaries (Serinus canaria), the song control circuit has been shown to undergo a remarkable change in morphology in response to exogenous testosterone (T). It is also well established that HVC, a telencephalic nucleus involved in song production, is significantly larger in males than in females. T regulates seasonal changes in HVC volume in males and exposure to exogenous T in adult females increases HVC volume and singing activity such that their song becomes more male-like in frequency and structure. However, whether there are sex differences in the ability of T to modulate changes in the song system and song behavior has not been investigated in canaries. In this study, we compared the effects of increasing doses of T on singing and song control nuclei volumes in adult male and female American Singer canaries exposed to identical environmental conditions. Males were castrated and all birds were placed on short days (8L:16D) for 8 weeks. Males and females were implanted either with a 2, 6 or 12 mm long Silastic™ implant filled with crystalline T or an empty 12 mm implant as control. Birds were then housed individually in sound attenuated chambers. Brains were collected from six birds from each group after 1 week or 3 weeks of treatment. Testosterone was not equally effective in increasing singing activity in both males and females. Changes in song quality and occurrence rate took place after a shorter latency in males than in females however, females did undergo marked changes in a number of measures of song behavior if given sufficient time. Males responded with an increase in HVC volume at all three doses. In females, T-induced changes in HVC volume only had limited amplitude and these volumes never reached male-typical levels a suggesting that there are sex differences in the neural substrate that responds to T. PMID:25260250

  18. Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens

    PubMed Central

    Lin, Philana Ling; Coleman, Teresa; Carney, Jonathan P. J.; Lopresti, Brian J.; Tomko, Jaime; Fillmore, Dan; Dartois, Veronique; Scanga, Charles; Frye, L. James; Janssen, Christopher; Klein, Edwin; Barry, Clifton E.

    2013-01-01

    Trials to test new drugs currently in development against tuberculosis in humans are impractical. All animal models to prioritize new regimens are imperfect, but nonhuman primates (NHPs) infected with Mycobacterium tuberculosis develop active tuberculosis (TB) disease with a full spectrum of lesion types seen in humans. Serial 2-deoxy-2-[18F]-fluoro-d-glucose (FDG) positron emission tomography (PET) with computed tomography (CT) imaging was performed on cynomolgus macaques during infection and chemotherapy with individual agents or the four-drug combination therapy most widely used globally. The size and metabolic activity of lung granulomas varied among animals and even within a single animal during development of disease. Individual granulomas within untreated animals had highly local and independent outcomes, some progressing in size and FDG uptake, while others waned, illustrating the highly dynamic nature of active TB. At necropsy, even untreated animals were found to have a proportion of sterile lesions consistent with the dynamics of this infection. A more marked reduction in overall metabolic activity in the lungs (decreased FDG uptake) was associated with effective treatment. A reduction in the size of individual lesions correlated with a lower bacterial burden at necropsy. Isoniazid treatment was associated with a transient increase in metabolic activity in individual lesions, whereas a net reduction occurred in most lesions from rifampin-treated animals. Quadruple-drug therapy resulted in the highest decrease in FDG uptake. The findings of PET-CT imaging may provide an important early correlate of the efficacy of novel combinations of new drugs that can be directly translated to human clinical trials. PMID:23796926

  19. Space and Place and the "American" Legacy: Female Protagonists and the Discovery of Self in Two Novels for Young Adults

    ERIC Educational Resources Information Center

    Glenn, Wendy J.

    2017-01-01

    This qualitative literary analysis explores the intersection of place, space, and identity in two novels for young adults to explore how the provision of a new physical place provides space for independence development among female teen protagonists and the implications of this development given the authors' identities as non-US authors writing…

  20. Tumor necrosis factor-alpha during neonatal brain development affects anxiety- and depression-related behaviors in adult male and female mice.

    PubMed

    Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

    2014-03-15

    A nascent literature suggests that neonatal infection is a risk factor for the development of brain, behavior and hypothalamic-pituitary-adrenal axis which can affect anxiety- and depression-related behaviors in later life. It has been documented that neonatal infection raises the concentrations of tumor necrosis factor-alpha (TNF-α) in neonate rodents and such infections may result in neonatal brain injury, at least in part, through pro-inflammatory cytokines. In addition, previous studies have shown that TNF-α is involved in cellular differentiation, neurogenesis and programmed cell death during the development of the central nervous system. We investigated for the first time whether neonatal exposure to TNF-α can affect body weight, stress-induced corticosterone (COR), anxiety- and depression-related behaviors in adult mice. In the present study, neonatal mice were treated to recombinant mouse TNF-α (0.2, 0.4, 0.7 and 1 μg/kg) or saline on postnatal days 3 and 5, then adult male and female mice were exposed to different behavioral tests. The results indicated that neonatal TNF-α treatment reduced body weight in neonatal period in both sexes. In addition, this study presents findings indicating that high doses of TNF- increase stress-induced COR levels, anxiety- and depression-related behaviors in adult males, but increase levels of anxiety without significantly influencing depression in adult female mice [corrected]. Our findings suggest that TNF-α exposure during neonatal period can alter brain and behavior development in a dose and sex-dependent manner in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Development of sexual behavior in free-ranging female Japanese macaques.

    PubMed

    Leca, Jean-Baptiste; Gunst, Noëlle; Vasey, Paul L

    2014-09-01

    We studied the development of sexual behaviors in female Japanese macaques (Macaca fuscata) living at Arashiyama, Japan, in a group where adult females routinely exhibit sexual interactions with both males and females. Our cross-sectional data on juvenile, adolescent, and adult females supported most of our predictions related to the learning hypothesis, which holds that adolescence serves to provide females with a period in which to practice adult female-like sexual behavioral patterns, including sexual solicitations, sexual mounts, and spatio-temporal coordination during consortships. We found evidence for a gradual acquisition of adult-like behavioral patterns (e.g., more frequent solicitations with body contact, more frequent complete mounts, more diverse solicitation patterns and complete mounting postures, and longer consortships involving prolonged inter-mount grasping behavior between partners), and a gradual disappearance of less effective immature behavioral patterns (e.g., less frequent non-contact solicitations, ambiguous mounting initiations, and incomplete mounts). We distinguished between three major categories of sexual behavioral patterns based on their speed of development, ranging from fast (e.g., diversity in mounting postures and genital stimulation during mounting) to slow (e.g., contact solicitations and grasping behavior between consortship partners), with some being intermediate (e.g., range of solicitation patterns and expression of complete mounts). This study showed that the emergence of both conceptive and non-conceptive adult sexual behaviors can be traced back to immature behavioral patterns in adolescent female Japanese macaques, with a major threshold occurring at the age of 4 years. © 2014 Wiley Periodicals, Inc.

  2. Pregnancy or stress decrease complexity of CA3 pyramidal neurons in the hippocampus of adult female rats.

    PubMed

    Pawluski, J L; Valença, A; Santos, A I M; Costa-Nunes, J P; Steinbusch, H W M; Strekalova, T

    2012-12-27

    Pregnancy is a time of distinct neural, physiological and behavioral plasticity in the female. It is also a time when a growing number of women are vulnerable to stress and experience stress-related diseases, such as depression and anxiety. However, the impact of stress during gestation on the neurobiology of the mother has yet to be determined, particularly with regard to changes in the hippocampus; a brain area that plays an important role in stress-related diseases. Therefore, the aim of the present study was to understand how stress and reproductive state may alter dendritic morphology of CA1 and CA3 pyramidal neurons in the hippocampus. To do this, adult age-matched pregnant and virgin female Wistar rats were divided into two conditions: (1) control and (2) stress. Females in the stress condition were restrained for 1h/day for the last 2 weeks of gestation and at matched time-points in virgin females. Females were sacrificed the day after the last restraint session and brains were processed for Golgi impregnation. Dendritic length and number of branch points were quantified for apical and basal regions of CA1 and CA3 pyramidal neurons. Results show that regardless of reproductive state, stressed females had significantly shorter apical dendrites and fewer apical branch points in CA3 pyramidal cells. In addition, pregnant females, regardless of stress exposure, had less complex CA3 pyramidal neurons, as measured by Sholl analysis. No differences between conditions were seen in morphology of CA1 pyramidal neurons. This work shows that both repeated restraint stress and pregnancy affect dendritic morphology by decreasing complexity of CA3, but not CA1, neurons in the hippocampus. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Development and validation of a liquid chromatography tandem mass spectrometry assay for the quantitation of a protein therapeutic in cynomolgus monkey serum.

    PubMed

    Zhao, Yue; Liu, Guowen; Angeles, Aida; Hamuro, Lora L; Trouba, Kevin J; Wang, Bonnie; Pillutla, Renuka C; DeSilva, Binodh S; Arnold, Mark E; Shen, Jim X

    2015-04-15

    We have developed and fully validated a fast and simple LC-MS/MS assay to quantitate a therapeutic protein BMS-A in cynomolgus monkey serum. Prior to trypsin digestion, a recently reported sample pretreatment method was applied to remove more than 95% of the total serum albumin and denature the proteins in the serum sample. The pretreatment procedure simplified the biological sample prior to digestion, improved digestion efficiency and reproducibility, and did not require reduction and alkylation. The denatured proteins were then digested with trypsin at 60 °C for 30 min and the tryptic peptides were chromatographically separated on an Acquity CSH column (2.1 mm × 50 mm, 1.7 μm) using gradient elution. One surrogate peptide was used for quantitation and another surrogate peptide was selected for confirmation. Two corresponding stable isotope labeled peptides were used to compensate variations during LC-MS detection. The linear analytical range of the assay was 0.50-500 μg/mL. The accuracy (%Dev) was within ± 5.4% and the total assay variation (%CV) was less than 12.0% for sample analysis. The validated method demonstrated good accuracy and precision and the application of the innovative albumin removal sample pretreatment method improved both assay sensitivity and robustness. The assay has been applied to a cynomolgus monkey toxicology study and the serum sample concentration data were in good agreement with data generated using a quantitative ligand-binding assay (LBA). The use of a confirmatory peptide, in addition to the quantitation peptide, ensured the integrity of the drug concentrations measured by the method. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Testing the 'Extreme Female Brain' Theory of Psychosis in Adults with Autism Spectrum Disorder with or without Co-Morbid Psychosis.

    PubMed

    Larson, Felicity V; Lai, Meng-Chuan; Wagner, Adam P; Baron-Cohen, Simon; Holland, Anthony J

    2015-01-01

    Males and females in the general population differ, on average, in their drive for empathizing (higher in females) and systemizing (higher in males). People with autism spectrum disorder (ASD) show a drive for systemizing over empathizing, irrespective of sex, which led to the conceptualisation of ASD as an 'extreme of the typical male brain'. The opposite cognitive profile, an 'extreme of the typical female brain', has been proposed to be linked to conditions such as psychosis and mania/hypomania. We compared an empathizing-over-systemizing bias (for short 'empathizing bias') in individuals with ASD, who had experienced psychotic illness (N = 64) and who had not (N = 71). There were overall differences in the distribution of cognitive style. Adults with ASD who had experienced psychosis were more likely to show an empathizing bias than adults with ASD who had no history of psychosis. This was modulated by IQ, and the group-difference was driven mainly by individuals with above-average IQ. In women with ASD and psychosis, the link between mania/hypomania and an empathizing bias was greater than in men with ASD. The bias for empathizing over systemizing may be linked to the presence of psychosis in people with ASD. Further research is needed in a variety of clinical populations, to understand the role an empathizing bias may play in the development and manifestation of mental illness.

  5. Neonatal programming with testosterone propionate reduces dopamine transporter expression in nucleus accumbens and methylphenidate-induced locomotor activity in adult female rats.

    PubMed

    Dib, Tatiana; Martínez-Pinto, Jonathan; Reyes-Parada, Miguel; Torres, Gonzalo E; Sotomayor-Zárate, Ramón

    2018-07-02

    Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50μLs.c.) or estradiol valerate (EV: 0.1mg/50μLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Amphetamine-induced incentive sensitization of sign-tracking behavior in adolescent and adult female rats

    PubMed Central

    Doremus-Fitzwater, Tamara L.; Spear, Linda P.

    2010-01-01

    Age-specific behavioral and neural characteristics may predispose adolescents to initiate and escalate use of alcohol and drugs. Adolescents may avidly seek novel experiences, including drugs of abuse, because of enhanced incentive motivation for drugs and natural rewards, perhaps especially when that incentive motivation is sensitized by prior drug exposure. Using a Pavlovian conditioned approach (PCA) procedure, sign-tracking (ST) and goal-tracking (GT) behavior was examined in amphetamine-sensitized and control adolescent and adult female Sprague-Dawley rats, with expression of elevated ST behavior used to index enhanced incentive motivation for reward-associated cues. Rats were first exposed to a sensitizing regimen of amphetamine injections (3.0 mg/kg/ml d-amphetamine per day) or given saline (0.9% w/v) once daily for 4 days. Expression of ST and GT was then examined over 8 days of PCA training consisting of 25 pairings of an 8-sec presentation of an illuminated lever immediately followed by response-independent delivery of a banana-flavored food pellet. Results showed that adults clearly displayed more ST behavior than adolescents, reflected via both more contacts with, and shorter latencies to approach, the lever. Prior amphetamine sensitization increased ST (but not GT) behaviors regardless of age. Thus, when indexed via ST, incentive motivation was found to be greater in adults than adolescents, with a prior history of amphetamine exposure generally sensitizing incentive motivation for cues predicting a food reward regardless of age. PMID:21534648

  7. Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus

    PubMed Central

    Rubins, Kathleen H.; Huggins, John W.; Fisher, Robert W.; Johnson, Anthony J.; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E.; Jahrling, Peter B.

    2011-01-01

    Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections – an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions. PMID:21998632

  8. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    PubMed

    Wahl-Jensen, Victoria; Cann, Jennifer A; Rubins, Kathleen H; Huggins, John W; Fisher, Robert W; Johnson, Anthony J; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E; Jahrling, Peter B

    2011-01-01

    Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  9. Oral administration of leaf extracts of Momordica charantia affect reproductive hormones of adult female Wistar rats

    PubMed Central

    Adewale, Osonuga Odusoga; Oduyemi, Osonuga Ifabunmi; Ayokunle, Osonuga

    2014-01-01

    Objective To determine the effect of graded doses of aqueous leaf extracts of Momordica charantia on fertility hormones of female albino rats. Methods Twenty adult, healthy, female Wistar rats were divided into four groups: low dose (LD), moderate dose (MD) and high dose (HD) groups which received 12.5 g, 25.0 g, 50.0 g of the leaf extract respectively and control group that was given with water ad libatum. Result Estrogen levels reduced by 6.40 nmol/L, 10.80 nmol/L and 28.00 nmol/L in the LD, MD and HD groups respectively while plasma progesterone of rats in the LD, MD and HD groups reduced by 24.20 nmol/L, 40.8 nmol/L and 59.20 nmol/L respectively. Conclusion Our study has shown that the antifertility effect of Momordica charantia is achieved in a dose dependent manner. Hence, cautious use of such medication should be advocated especially when managing couples for infertility. PMID:25183143

  10. Effects of environmental variables on surface temperature of breeding adult female northern elephant seals, Mirounga angustirostris, and pups.

    PubMed

    Codde, Sarah A; Allen, Sarah G; Houser, Dorian S; Crocker, Daniel E

    2016-10-01

    Pinnipeds spend extended periods of time on shore during breeding, and some temperate species retreat to the water if exposed to high ambient temperatures. However, female northern elephant seals (Mirounga angustirostris) with pups generally avoid the water, presumably to minimize risks to pups or male harassment. Little is known about how ambient temperature affects thermoregulation of well insulated females while on shore. We used a thermographic camera to measure surface temperature (T s ) of 100 adult female elephant seals and their pups during the breeding season at Point Reyes National Seashore, yielding 782 thermograms. Environmental variables were measured by an onsite weather station. Environmental variables, especially solar radiation and ambient temperature, were the main determinants of mean and maximum T s of both females and pups. An average of 16% of the visible surface of both females and pups was used as thermal windows to facilitate heat loss and, for pups, this area increased with solar radiation. Thermal window area of females increased with mean T s until approximately 26°C and then declined. The T s of both age classes were warmer than ambient temperature and had a large thermal gradient with the environment (female mean 11.2±0.2°C; pup mean 14.2±0.2°C). This large gradient suggests that circulatory adjustments to bypass blubber layers were sufficient to allow seals to dissipate heat under most environmental conditions. We observed the previously undescribed behavior of females and pups in the water and determined that solar radiation affected this behavior. This may have been possible due to the calm waters at the study site, which reduced the risk of neonates drowning. These results may predict important breeding habitat features for elephant seals as solar radiation and ambient temperatures change in response to changing climate. Published by Elsevier Ltd.

  11. Investigation into the mechanism(s) that leads to platelet decreases in cynomolgus monkeys during administration of ISIS-104838, a 2'-MOE-modified antisense oligonucleotide.

    PubMed

    Narayanan, P K; Shen, L; Curtis, B R; Bourdon, M; Nolan, J P; Zhou, F; Christian, B; Gupta, S; Schaubhut, J L; Greenlee, S; Hoffmaster, C; Burel, S; Witztum, J L; Engelhardt, J A; Henry, S P

    2018-05-29

    ISIS 104838, a 2'-O-methoxyethyl (2'-MOE)-modified antisense oligonucleotide (ASO), causes a moderate, reproducible, dose-dependent, but self-limiting decrease in platelet (PLT) counts in monkeys and humans. To determine the etiology of PLT decrease in cynomolgus monkeys, a 12-week repeat dose toxicology study in 5 cynomolgus monkeys given subcutaneous injections of ISIS 104838 (30 to 60 mg/kg/week). Monkeys were also injected intravenously with 111In-oxine-labeled PLTs to investigate PLT sequestration. In response to continued dosing, PLT counts were decreased by 50 to 90% by day 30 in all monkeys. PLT decreases were accompanied by 2- to 4.5-fold increases in immunoglobulin M(IgM), which were typified by a 2-to-5-fold increase in anti-platelet factor 4 (PF4) IgM and anti-PLT IgM, respectively. Monocyte chemotactic protein 1 (MCP-1) increased upon dosing of ISIS 104838, concomitant with a 2- to 6-fold increase in monocyte-derived extracellular vesicles (EVs), indicating monocyte activation but not PLT activation. Despite a 2- to- 3-fold increase in von Willebrand factor (VWF) antigen in all monkeys following ASO administration, only two monkeys showed a 2 to 4-fold increase in endothelial EVs. Additionally, a 25-45% increase in PLT sequestration in liver and spleen was also observed. Collectively, these results suggest the overall increase in total IgM, anti-PLT IgM and/or anti-PF4 IgM, in concert with monocyte activation contributed to increased PLT sequestration in spleen and liver, leading to decreased PLTs in peripheral blood.

  12. Assessing the Long-Term Effects of EMDR: Results from an 18-Month Follow-Up Study with Adult Female Survivors of CSA

    ERIC Educational Resources Information Center

    Edmond, Tonya; Rubin, Allen

    2004-01-01

    This 18-month follow-up study builds on the findings of a randomized experimental evaluation that found qualified support for the short-term effectiveness of Eye Movement Desensitization and Reprocessing (EMDR) in reducing trauma symptoms among adult female survivors of childhood sexual abuse (CSA). The current study provides preliminary evidence…

  13. Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

    PubMed Central

    Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

    2016-01-01

    Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

  14. Prenatal Exposure to Unconventional Oil and Gas Operation Chemical Mixtures Altered Mammary Gland Development in Adult Female Mice.

    PubMed

    Sapouckey, Sarah A; Kassotis, Christopher D; Nagel, Susan C; Vandenberg, Laura N

    2018-03-01

    Unconventional oil and gas (UOG) operations, which combine hydraulic fracturing (fracking) and directional drilling, involve the use of hundreds of chemicals, including many with endocrine-disrupting properties. Two previous studies examined mice exposed during early development to a 23-chemical mixture of UOG compounds (UOG-MIX) commonly used or produced in the process. Both male and female offspring exposed prenatally to one or more doses of UOG-MIX displayed alterations to endocrine organ function and serum hormone concentrations. We hypothesized that prenatal UOG-MIX exposure would similarly disrupt development of the mouse mammary gland. Female C57Bl/6 mice were exposed to ~3, ~30, ~ 300, or ~3000 μg/kg/d UOG-MIX from gestational day 11 to birth. Although no effects were observed on the mammary glands of these females before puberty, in early adulthood, females exposed to 300 or 3000 μg/kg/d UOG-MIX developed more dense mammary epithelial ducts; females exposed to 3 μg/kg/d UOG-MIX had an altered ratio of apoptosis to proliferation in the mammary epithelium. Furthermore, adult females from all UOG-MIX-treated groups developed intraductal hyperplasia that resembled terminal end buds (i.e., highly proliferative structures typically seen at puberty). These results suggest that the mammary gland is sensitive to mixtures of chemicals used in UOG production at exposure levels that are environmentally relevant. The effect of these findings on the long-term health of the mammary gland, including its lactational capacity and its risk of cancer, should be evaluated in future studies. Copyright © 2018 Endocrine Society.

  15. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats.

    PubMed

    Camats, N; García, F; Parrilla, J J; Calaf, J; Martín-Mateo, M; Caldés, M Garcia

    2009-10-02

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F(0)) with reproductive parameters, and in the somatic cells of the resulting foetuses (F(1)) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  16. Methylphenidate mediated change in prosody is specific to the performance of a cognitive task in female adult ADHD patients.

    PubMed

    Bloch, Yuval; Aviram, Shai; Neeman, Ronnie; Braw, Yoram; Nitzan, Uriel; Maoz, Hagai; Mimouni-Bloch, Aviva

    2015-01-01

    Prosody production is highly personalized, related to both the emotional and cognitive state of the speaker and to the task being performed. Fundamental frequency (F main) is a central measurable feature of prosody, associated with having an attention deficit hyperactive disorder (ADHD). Since methylphenidate is an effective therapy for ADHD, we hypothesized that it will affect the fundamental frequency of ADHD patients. The answers of 32 adult ADHD patients were recorded while performing two computerized tasks (cognitive and emotional). Evaluations were performed at baseline and an hour after patients received methylphenidate. A significant effect of methylphenidate was observed on the fundamental frequency, as opposed to other parameters, of prosody. This change was evident while patients performed a cognitive, as opposed to an emotional, task. This change was seen in the 14 female ADHD patients but not in the 18 male ADHD patients. The fundamental frequency while performing a cognitive task without methylphenidate was not different in the female ADHD group, from 22 female controls. This pilot study supports prosodic changes as possible objective and accessible dynamic biological marker of treatment responses specifically in female ADHD.

  17. Gestational N-hexane inhalation alters the expression of genes related to ovarian hormone production and DNA methylation states in adult female F1 rat offspring.

    PubMed

    Li, Hong; Zhang, Chenyun; Ni, Feng; Guo, Suhua; Wang, Wenxiang; Liu, Jing; Lu, Xiaoli; Huang, Huiling; Zhang, Wenchang

    2015-12-15

    Research has revealed that n-hexane can disrupt adult female endocrine functions; however, few reports have focused on endocrine changes in adult F1 females after maternal exposure during gestation. In this study, female Wistar rats inhaled 100, 500, 2500, or 12,500 ppm n-hexane for 4 h daily during their initial 20 gestational days. The F1 female offspring exhibited abnormal oestrus cycles. Compared with the controls, the in vitro-cultured ovarian granulosa cells of the 12,500 ppm group showed significantly reduced in vitro progesterone and oestradiol secretion. Elevated progesterone secretion was observed in the 500 ppm group, and decreased and significantly upregulated mRNA expression of the Star, Cyp11a1, Cyp17a1, and Hsd3b genes was observed in the 12,500 ppm and 500 ppm groups, respectively. The protein expression levels were consistent with the mRNA expression levels. Methylation screening of the promoter regions of these genes was performed using MeDIP-chip and confirmed by methylation-sensitive high-resolution melting (MS-HRM), and the observed methylation state changes of the promoter regions were correlated with the gene expression levels. The results suggest that the hormone levels in the female offspring after gestational n-hexane inhalation correspond to the expression levels and DNA methylation states of the hormone production genes. Copyright © 2015. Published by Elsevier Ireland Ltd.

  18. Are 1994 alcohol production and the sales deregulation policy in Japan associated with increased road traffic fatalities among adult and teenage males and females in Japan?

    PubMed

    Desapriya, Ediriweera; Fujiwara, Takeo; Scime, Giulia; Sasges, Deborah; Pike, Ian; Shimizu, Shinji

    2009-10-01

    International studies have shown a significant association between alcohol availability and traffic crashes that involve alcohol-impaired drivers. A key limitation to previous alcohol availability and motor vehicle crash (MVC) evaluation research is the assumption of population homogeneity in responding to the policies. The present analysis focuses on the evaluation of the impact of alcohol availability on different segments of the Japanese population by comparing MVC fatality rates from before and after implementation of the alcohol deregulation policy in 1994. Poisson regression with robust standard error was used to model the before-to-after change in incidence rate ratios (IRR) in adult males, adult females, teenage males and teenage females. To control potential confounders, unemployment rate, vehicle miles of travel (VMT), vehicle registration, and number of drivers licensed in Japan were added to the model. The exponents of the fitted coefficients are equivalent to incidence rate ratios. Implementation of the policy deregulating alcohol sales and production did not appear to increase traffic fatalities among adult or teenage males or females in Japan. We found that male adult fatalities demonstrated a statistically significant decline following enactment of the deregulation policy in 1994. Contrary to previous research, the findings of this study demonstrated lower rates of fatalities and higher compliance with alcohol-related driving legislation in Japanese society following implementation of the deregulation policy in 1994. Further well designed, nonaligned studies on alcohol availability and traffic fatalities in other countries are urgently needed.

  19. Survival of female Lesser Scaup: Effects of body size, age, and reproductive effort

    USGS Publications Warehouse

    Rotella, J.J.; Clark, R.G.; Afton, A.D.

    2003-01-01

    In birds, larger females generally have greater breeding propensity, reproductive investment, and success than do smaller females. However, optimal female body size also depends on how natural selection acts during other parts of the life cycle. Larger female Lesser Scaup (Aythya affinis) produce larger eggs than do smaller females, and ducklings from larger eggs survive better than those hatching from smaller eggs. Accordingly, we examined patterns of apparent annual survival for female scaup and tested whether natural selection on female body size primarily was stabilizing, a frequent assumption in studies of sexually dimorphic species in which males are the larger sex, or was directional, counter-acting reproductive advantages of large size. We estimated survival using mark-recapture methods for individually marked females from two study sites in Canada (Erickson, Manitoba; St. Denis, Saskatchewan). Structurally larger (adults) and heavier (ducklings) females had lower survival than did smaller individuals in Manitoba; no relationship was detected in adults from Saskatchewan. Survival of adult females declined with indices of increasing reproductive effort at both sites; consequently, the cost of reproduction could explain age-related patterns of breeding propensity in scaup. Furthermore, if larger females are more likely to breed than are smaller females, then cost of reproduction also may help explain why survival was lower for larger females. Overall, we found that advantages of large body size of female scaup during breeding or as young ducklings apparently were counteracted by natural selection favoring lightweight juveniles and structurally smaller adult females through higher annual survival.

  20. Prenatal Stress Impairs Spatial Learning and Memory Associated with Lower mRNA Level of the CAMKII and CREB in the Adult Female Rat Hippocampus.

    PubMed

    Sun, Hongli; Wu, Haibin; Liu, Jianping; Wen, Jun; Zhu, Zhongliang; Li, Hui

    2017-05-01

    Prenatal stress (PS) results in various behavioral and emotional alterations observed in later life. In particular, PS impairs spatial learning and memory processes but the underlying mechanism involved in this pathogenesis still remains unknown. Here, we reported that PS lowered the body weight in offspring rats, particularly in female rats, and impaired spatial learning and memory of female offspring rats in the Morris water maze. Correspondingly, the decreased CaMKII and CREB mRNA in the hippocampus were detected in prenatally stressed female offspring, which partially explained the effect of PS on the spatial learning and memory. Our findings suggested that CaMKII and CREB may be involved in spatial learning and memory processes in the prenatally stressed adult female offspring.

  1. Determinants of female dispersal in Thomas langurs.

    PubMed

    Sterck, E H

    1997-01-01

    Female dispersal occurs in a number of primate species. It may be related to: avoidance of inbreeding, reduction in food competition, reduction of predation risk, or avoidance of infanticide in combination with mate choice. Female dispersal was studied for a 5-year period in a wild population of Thomas langurs (Presbytis thomasi) that lived in one-male multi-female groups. Juvenile and adult individuals of both sexes were seen to disperse. Females appeared to transfer unhindered between groups, mostly from a larger group to a recently formed smaller one. They transferred without their infants and when not pregnant, and seemed to transfer preferentially during periods when extra-group males were harassing their group. During these inter-group encounters extra-group males seemed to try to commit infanticide. Thus, the timing of female transfer was probably closely linked to infanticide avoidance. Moreover, females seemed to transfer when the resident male of their group was no longer a good protector. The observations in the present study suggest that females transferred to reduce the risk of infanticide. Female dispersal may have another ultimate advantage as well, namely inbreeding avoidance. Due to the dispersal of both females and males the social organization of Thomas langurs was rather fluid. New groups were formed when females joined a male; male takeovers were not observed. Bisexual groups had only a limited life span, because all adult females of a bisexual group could emigrate. This pattern of unhindered female dispersal affects male reproductive strategies, and in particular it might lead to infanticidal behavior during inter-group encounters.

  2. Larval Competition Reduces Body Condition in the Female Seed Beetle, Callosobruchus maculatus

    PubMed Central

    Schade, Daynika J.; Vamosi, Steven M.

    2012-01-01

    Early body condition may be important for adult behavior and fitness, and is impacted by a number of environmental conditions and biotic interactions. Reduced fecundity of adult females exposed to larval competition may be caused by reduced body condition or shifts in relative body composition, yet these mechanisms have not been well researched. Here, body mass, body size, scaled body mass index, and two body components (water content and lean dry mass) of adult Callosobruchus maculatus (Fabricius) (Coleoptera: Chrysomelidae: Bruchinae) females exposed to larval competition or reared alone were examined. Experimental females emerged at significantly smaller body mass and body size than control females. Additionally, scaled body mass index and water content, but not lean dry mass, were significantly reduced in experimental females. To our knowledge, these are the first results that demonstrate a potential mechanism for previously documented direct effects of competition on fecundity in female bruchine beetles. PMID:22954282

  3. Larval competition reduces body condition in the female seed beetle, Callosobruchus maculatus.

    PubMed

    Schade, Daynika J; Vamosi, Steven M

    2012-01-01

    Early body condition may be important for adult behavior and fitness, and is impacted by a number of environmental conditions and biotic interactions. Reduced fecundity of adult females exposed to larval competition may be caused by reduced body condition or shifts in relative body composition, yet these mechanisms have not been well researched. Here, body mass, body size, scaled body mass index, and two body components (water content and lean dry mass) of adult Callosobruchus maculatus (Fabricius) (Coleoptera: Chrysomelidae: Bruchinae) females exposed to larval competition or reared alone were examined. Experimental females emerged at significantly smaller body mass and body size than control females. Additionally, scaled body mass index and water content, but not lean dry mass, were significantly reduced in experimental females. To our knowledge, these are the first results that demonstrate a potential mechanism for previously documented direct effects of competition on fecundity in female bruchine beetles.

  4. Male versus Female Attitudes toward Stuttering

    ERIC Educational Resources Information Center

    St. Louis, Kenneth O.

    2012-01-01

    Purpose: The study investigated the extent to which differences existed between public attitudes of males versus females. Method: One hundred adults, 50 males and 50 females, were chosen at random from each of 50 study samples comprising a total of 3371 respondents in a database archive who had completed the "Public Opinion Survey of Human…

  5. Estimating natal dispersal movement rates of female European ducks with multistate modeling

    USGS Publications Warehouse

    Blums, P.; Nichols, J.D.; Hines, J.E.; Lindberg, M.S.; Mednis, A.

    2003-01-01

    1. We used up to 34 years of capture-recapture data from about 22,100 new releases of day-old female ducklings and multistate modelling to test predictions about the influence of environmental, habitat and management factors on natal dispersal probability of three species of ducks within the Engure Marsh, Latvia. 2. The mean natal dispersal distances were very similar (c . 0?6-0?7 km) for all three species and were on average 2?7 times greater than breeding dispersal distances recorded within the same study system. 3. We were unable to confirm the kinship hypothesis and found no evidence that young first-nesting females nested closer to their relatives (either mother or sister) than to the natal nest. 4. Young female northern shovelers, like adults, moved from small islands to the large island when water level was high and vice versa when water level was low before the construction of elevated small islands. Movement probabilities between the two strata were much higher for young shovelers than adults, suggesting that young birds had not yet developed strong fidelity to the natal site. Movements of young female tufted ducks, unlike those of shovelers, were not dependent on water level fluctuations and reflected substantial flexibility in choice of first nesting sites. 5. Data for young birds supported our earlier conclusion that common pochard nesting habitats in black-headed gull colonies were saturated during the entire study period. Young females, like the two adult age groups, moved into and out of colonies with similar probability. Fidelity probability of female pochards to each stratum increased with age, being the lowest (0?62) for young (DK) females, intermediate (0?78) for yearlings (SY) and the highest (0?84) for adult (ASY) females. 6. Young female tufted ducks, like adults, showed higher probabilities of moving from islands to emergent marshes when water levels were higher both before and after habitat management. The relationship between the spring

  6. Tradition over trend: Neighboring chimpanzee communities maintain differences in cultural behavior despite frequent immigration of adult females.

    PubMed

    Luncz, Lydia V; Boesch, Christophe

    2014-07-01

    The notion of animal culture has been well established mainly through research aiming at uncovering differences between populations. In chimpanzees (Pan troglodytes verus), cultural diversity has even been found in neighboring communities, where differences were observed despite frequent immigration of individuals. Female chimpanzees transfer at the onset of sexual maturity at an age, when the behavioral repertoire is fully formed. With immigrating females, behavioral variety enters the group. Little is known about the diversity and the longevity of cultural traits within a community. This study is building on previous findings of differences in hammer selection when nut cracking between neighboring communities despite similar ecological conditions. We now further investigated the diversity and maintenance of cultural traits within one chimpanzee community and were able to show high levels of uniformity in group-specific behavior. Fidelity to the behavior pattern did not vary between dispersing females and philopatric males. Furthermore, group-specific tool selection remained similar over a period of 25 years. Additionally, we present a study case on how one newly immigrant female progressively behaved more similar to her new group, suggesting that the high level of similarity in behavior is actively adopted by group members possibly even when originally expressing the behavior in another form. Taken together, our data support a cultural transmission process in adult chimpanzees, which leads to persisting cultural behavior of one community over time. © 2014 Wiley Periodicals, Inc.

  7. Long term effects of exposure to automobile exhaust on the pulmonary function of female adults in Tokyo, Japan

    PubMed Central

    Sekine, K; Shima, M; Nitta, Y; Adachi, M

    2004-01-01

    Aims: To investigate the chronic effects of air pollution caused mainly by automobiles in healthy adult females. Methods: Respiratory symptoms were investigated in 5682 adult females who had lived in the Tokyo metropolitan area for three years or more in 1987; 733 of them were subjected to pulmonary function tests over eight years from 1987 to 1994. The subjects were divided into three groups by the level of air pollution they were exposed to during the study period. The concentrations of nitrogen dioxide and suspended particulate matter were the highest in group 1, and the lowest in group 3. Results: The prevalence rates of respiratory symptoms in group 1 were higher than those in groups 2 and 3, except for wheezing. Multiple logistic regression analysis showed significant differences in persistent phlegm and breathlessness. The subjects selected for the analysis of pulmonary function were 94, 210, and 102 females in groups 1, 2, and 3, respectively. The annual mean change of FEV1 in group 1 was the largest (-0.020 l/y), followed by that in group 2 (-0.015 l/y), and that in group 3 (-0.009 l/y). Testing for trends showed a significant larger decrease of FEV1 with the increase in the level of air pollution. Conclusions: The subjects living in areas with high levels of air pollution showed higher prevalence rates of respiratory symptoms and a larger decrease of FEV1 compared with those living in areas with low levels of air pollution. Since the traffic density is larger in areas with high air pollution, the differences among the groups may reflect the effect of air pollution attributable to particulate matter found in automobile exhaust. PMID:15031394

  8. Generation, cryopreservation, function and in vivo persistence of ex-vivo expanded cynomolgus monkey regulatory T cells

    PubMed Central

    Guo, Hao; Zhang, Hong; Lu, Lien; Ezzelarab, Mohamed B.; Thomson, Angus W.

    2015-01-01

    We expanded flow-sorted Foxp3+ cynomolgus monkey regulatory T cells (Treg) >1000-fold after three rounds of stimulation with anti-CD3 mAb-loaded artificial antigen-presenting cells, rapamycin (first round only) and IL-2. The expanded Treg maintained their expression of Treg signature markers, CD25, CD27, CD39, Foxp3, Helios, and CTLA-4, as well as CXCR3, which plays an important role in T cell migration to sites of inflammation. In contrast to expanded effector T cells (Teff), expanded Treg produced minimal IFN-γ and IL-17 and no IL-2 and potently suppressed Teff proliferation. Following cryopreservation, thawed Treg were less viable than their freshly-expanded counterparts, although no significant changes in phenotype or suppressive ability were observed. Additional rounds of stimulation/expansion restored maximal viability. Furthermore, adoptively-transferred autologous Treg expanded from cryopreserved second round stocks and labeled with CFSE or VPD450 were detected in blood and secondary lymphoid tissues of normal or immunosuppressed recipients at least two months after their systemic infusion. PMID:25732601

  9. Female gonadal shielding with automatic exposure control increases radiation risks.

    PubMed

    Kaplan, Summer L; Magill, Dennise; Felice, Marc A; Xiao, Rui; Ali, Sayed; Zhu, Xiaowei

    2018-02-01

    Gonadal shielding remains common, but current estimates of gonadal radiation risk are lower than estimated risks to colon and stomach. A female gonadal shield may attenuate active automatic exposure control (AEC) sensors, resulting in increased dose to colon and stomach as well as to ovaries outside the shielded area. We assess changes in dose-area product (DAP) and absorbed organ dose when female gonadal shielding is used with AEC for pelvis radiography. We imaged adult and 5-year-old equivalent dosimetry phantoms using pelvis radiograph technique with AEC in the presence and absence of a female gonadal shield. We recorded DAP and mAs and measured organ absorbed dose at six internal sites using film dosimetry. Female gonadal shielding with AEC increased DAP 63% for the 5-year-old phantom and 147% for the adult phantom. Absorbed organ dose at unshielded locations of colon, stomach and ovaries increased 21-51% in the 5-year-old phantom and 17-100% in the adult phantom. Absorbed organ dose sampled under the shield decreased 67% in the 5-year-old phantom and 16% in the adult phantom. Female gonadal shielding combined with AEC during pelvic radiography increases absorbed dose to organs with greater radiation sensitivity and to unshielded ovaries. Difficulty in proper use of gonadal shields has been well described, and use of female gonadal shielding may be inadvisable given the risks of increasing radiation.

  10. Species differences in behavior and cell proliferation/survival in the adult brains of female meadow and prairie voles

    PubMed Central

    Pan, Yongliang; Liu, Yan; Lieberwirth, Claudia; Zhang, Zhibin; Wang, Zuoxin

    2016-01-01

    Microtine rodents display diverse patterns of social organization and behaviors, and thus provide a useful model for studying the effects of the social environment on physiology and behavior. The current study compared the species differences and the effects of oxytocin (OT) on anxiety-like, social affiliation, and social recognition behaviors in female meadow voles (Microtus pennsylvanicus) and prairie voles (M. ochrogaster). Furthermore, cell proliferation and survival in the brains of adult female meadow and prairie voles were compared. We found that female meadow voles displayed a higher level of anxiety-like behavior but lower levels of social affiliation and social recognition compared to female prairie voles. In addition, meadow voles showed lower levels of cell proliferation (measured by Ki67 staining) and cell survival (measured by BrdU staining) in the ventromedial hypothalamus (VMH) and amygdala (AMY), but not the dentate gyrus of the hippocampus (DG), than prairie voles. Interestingly, the numbers of new cells in the VMH and AMY, but not DG, also correlated with anxiety-like, social affiliation, and social recognition behaviors in a brain region-specific manner. Finally, central OT treatment (200 ng/kg, icv) did not lead to changes in behavior or cell proliferation/survival in the brain. Together, these data indicate a potential role of cell proliferation/survival in selected brain areas on different behaviors between vole species with distinct life strategies. PMID:26708743

  11. Estradiol and GPER Activation Differentially Affect Cell Proliferation but Not GPER Expression in the Hippocampus of Adult Female Rats

    PubMed Central

    Duarte-Guterman, Paula; Lieblich, Stephanie E.; Chow, Carmen; Galea, Liisa A. M.

    2015-01-01

    Estradiol increases cell proliferation in the dentate gyrus of the female rodent but it is not known whether the G protein-coupled estrogen receptor (GPER), a membrane receptor, is involved in this process, nor whether there are regional differences in estradiol’s effects on cell proliferation. Thus, we investigated whether estradiol exerts its effects on cell proliferation in the dorsal and ventral dentate gyrus through GPER, using the GPER agonist, G1, and antagonist, G15. Ovariectomized adult female rats received a single injection of either: 17β-estradiol (10 μg), G1 (0.1, 5, 10 μg), G15 (40 μg), G15 and estradiol, or vehicle (oil, DMSO, or oil+DMSO). After 30 min, animals received an injection of bromodeoxyuridine (BrdU) and were perfused 24 h later. Acute treatment with estradiol increased, while the GPER agonist G1 (5 μg) decreased, the number of BrdU+ cells in the dentate gyrus relative to controls. The GPER antagonist, G15 increased the number of BrdU+ cells relative to control in the dorsal region and decreased the number of BrdU+ cells in the ventral region. However, G15 treatment in conjunction with estradiol partially eliminated the estradiol-induced increase in cell proliferation in the dorsal dentate gyrus. Furthermore, G1 decreased the expression of GPER in the dentate gyrus but not the CA1 and CA3 regions of the hippocampus. In summary, we found that activation of GPER decreased cell proliferation and GPER expression in the dentate gyrus of young female rats, presenting a potential and novel estrogen-independent role for this receptor in the adult hippocampus. PMID:26075609

  12. Estradiol and GPER Activation Differentially Affect Cell Proliferation but Not GPER Expression in the Hippocampus of Adult Female Rats.

    PubMed

    Duarte-Guterman, Paula; Lieblich, Stephanie E; Chow, Carmen; Galea, Liisa A M

    2015-01-01

    Estradiol increases cell proliferation in the dentate gyrus of the female rodent but it is not known whether the G protein-coupled estrogen receptor (GPER), a membrane receptor, is involved in this process, nor whether there are regional differences in estradiol's effects on cell proliferation. Thus, we investigated whether estradiol exerts its effects on cell proliferation in the dorsal and ventral dentate gyrus through GPER, using the GPER agonist, G1, and antagonist, G15. Ovariectomized adult female rats received a single injection of either: 17β-estradiol (10 μg), G1 (0.1, 5, 10 μg), G15 (40 μg), G15 and estradiol, or vehicle (oil, DMSO, or oil+DMSO). After 30 min, animals received an injection of bromodeoxyuridine (BrdU) and were perfused 24 h later. Acute treatment with estradiol increased, while the GPER agonist G1 (5 μg) decreased, the number of BrdU+ cells in the dentate gyrus relative to controls. The GPER antagonist, G15 increased the number of BrdU+ cells relative to control in the dorsal region and decreased the number of BrdU+ cells in the ventral region. However, G15 treatment in conjunction with estradiol partially eliminated the estradiol-induced increase in cell proliferation in the dorsal dentate gyrus. Furthermore, G1 decreased the expression of GPER in the dentate gyrus but not the CA1 and CA3 regions of the hippocampus. In summary, we found that activation of GPER decreased cell proliferation and GPER expression in the dentate gyrus of young female rats, presenting a potential and novel estrogen-independent role for this receptor in the adult hippocampus.

  13. Separation-Individuation in Female Adult Development.

    ERIC Educational Resources Information Center

    Mullins, Deborah

    This study examined separation-individuation development issues for young adult women, from the perspective of object-relations theory. Its purpose was to explore a woman's perception of her relationship with mother as it is affected by age and request for psychotherapy as well as the relationship between mother-daughter bond and personality…

  14. Assessing dental caries prevalence in African-American youth and adults.

    PubMed

    Seibert, Wilda; Farmer-Dixon, Cherae; Bolden, Theodore E; Stewart, James H

    2004-01-01

    It has been well documented that dental caries affect millions of children in the USA with the majority experiencing decay by the late teens. This is especially true for low-income minorities. The objective of this descriptive study was to determine dental caries prevalence in a sample of low-income African-American youth and adults. A total of 1034 individuals were examined. They were divided into two age groups: youth, 9-19 years and adults, 20-39 years. Females comprised approximately 65 percent (64.5) of the study group. The DMFT Index was used to determine caries prevalence in this study population. The DMFT findings showed that approximately 73 percent (72.9 percent) of the youth had either decayed, missing or filled teeth. Male youth had slightly higher DMFT mean scores than female youth: male mean = 7.93, standard error = 0.77, female mean = 7.52, standard error = 0.36; however, as females reached adulthood their DMFT scores increased substantially, mean = 15.18, standard error = 0.36. Caries prevalence was much lower in male adults, DMFT, mean = 7.22, standard error of 0.33. The decayed component for female adults mean score was 6.81, a slight increase over adult males, mean = 6.58. Although there were few filled teeth in both age groups, female adults had slightly more filled teeth than male adults, females mean = 2.91 vs. males; however, adult males experienced slightly more missing teeth, mean = 5.62 as compared to adult females, mean = 5.46. n = 2.20. Both female and male adults had an increase in missing teeth. As age increased there was a significant correlation among decayed, missing and filled teeth as tested by Analysis of Variance (ANOVA), p < 0.01. A significant correlation was found between filled teeth by sex, p < .005. We conclude that caries prevalence was higher in female and male youth, but dental caries increased more rapidly in females as they reached adulthood.

  15. A sex risk reduction text-message program for young adult females discharged from the emergency department.

    PubMed

    Suffoletto, Brian; Akers, Aletha; McGinnis, Kathleen A; Calabria, Jaclyn; Wiesenfeld, Harold C; Clark, Duncan B

    2013-09-01

    To pilot test a text message (SMS) sex risk reduction program among at-risk young adult female patients discharged from an emergency department (ED). A convenience sample of 52 female patients with hazardous drinking behavior and recent risky sexual encounters were recruited from an urban ED and randomized to the SMS program (n = 23) or a control group (n = 29). All participants completed a web-based questionnaire in the ED and at 3-month follow-up. For 12 weeks, SMS participants were asked to report whether they had a risky sexual encounter in the past week, received theory-based feedback, and were asked if they were willing set a goal to refrain from having another risky encounter. Thirty-nine percent of SMS participants completed all weeks of SMS reports, and noncompletion increasing from 12% on week 1 to a 33% by week 12. Three-month follow-up was completed in 56% of participants. In the intervention group, there was an increase in the proportion with condom use with last vaginal sex from 20% (95% CI 4%-48%) to 53% (95% CI 27%-79%) and an increase in always condom use over the past 28 days from 0% (95% CI 0%-22%) to 33% (95% CI 12%-62%). These changes were not statistically different from control participants. SMS programs may be useful to reduce risk for sexually transmitted diseases among at-risk young adults being discharged from the ED. Future trials should examine ways to improve adherence to SMS dialog over time and measure objective outcomes in a larger sample. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  16. Retinoid metabolism and transplacental pharmacokinetics in the cynomolgus monkey following a nonteratogenic dosing regimen with all-trans-retinoic acid.

    PubMed

    Tzimas, G; Nau, H; Hendrickx, A G; Peterson, P E; Hummler, H

    1996-11-01

    Retinoids often exhibit a complex metabolic pattern and differential transplacental kinetics, which make it difficult to pinpoint the proximate compound responsible for the observed teratogenic effect. We have therefore studied the pharmacokinetics and metabolism of all-trans-retinoic acid (all-trans-RA) in cynomolgus monkeys following application of a nonteratogenic dosing regimen and compared the results with corresponding data from a previous study with a teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994) Teratology 50:184-193]. All-trans-RA was administered to pregnant cynomolgus monkeys (Macaca fascicularis) by nasogastric intubation at a dose of 5 mg/kg body wt once daily from gestational day (GD) 16 to 26 and twice daily at 8-h intervals from GD 27 to 31. Examination of the fetuses of four dams on GD 100 +/- 2 showed no embryotoxic or teratogenic effects of the applied dosing regimen (Experiment 1). Maternal plasma retinoid pharmacokinetics on GD 16, 26, and 31 as well as embryonic retinoid profiles after the last drug administration on GD 31 were determined in thirteen further dams (Experiment 2). All-trans-RA reached much lower plasma concentrations after the last two treatments on GD 31 than after the first one on GD 16 and the eleventh one on GD 26 (0-24-h area-under-the-concentration-time-curve (AUC) values: 104 +/- 59 ng x h/ml (after the last treatment on GD 31), 189 +/- 110 (GD 16) and 393 +/- 305 ng x h/ml (GD 26). The predominant plasma metabolites of all-trans-RA were its beta-glucuronide and the beta-glucuronide of all-trans-4-oxo-RA. Both of these retinoids accumulated in the plasma during the period of treatment and displayed AUC values 5- to 30-fold higher than those of all-trans-RA. Embryonic concentrations of all-trans-RA were not increased over endogenous levels after the last administration on GD 31 when plasma concentrations were low. To evaluate the placental transport of all-trans-RA in the presence of high plasma

  17. Immunization with recombinant V10 protects cynomolgus macaques from lethal pneumonic plague.

    PubMed

    Cornelius, Claire A; Quenee, Lauriane E; Overheim, Katie A; Koster, Frederick; Brasel, Trevor L; Elli, Derek; Ciletti, Nancy A; Schneewind, Olaf

    2008-12-01

    Vaccine and therapeutic strategies that prevent infections with Yersinia pestis have been sought for over a century. Immunization with live attenuated (nonpigmented) strains and immunization with subunit vaccines containing recombinant low-calcium-response V antigen (rLcrV) and recombinant F1 (rF1) antigens are considered effective in animal models. Current antiplague subunit vaccines in development for utilization in humans contain both antigens, either as equal concentrations of the two components (rF1 plus rLcrV) or as a fusion protein (rF1-rLcrV). Here, we show that immunization with either purified rLcrV (a protein at the tip of type III needles) or a variant of this protein, recombinant V10 (rV10) (lacking amino acid residues 271 to 300), alone or in combination with rF1, prevented pneumonic lesions and disease pathogenesis. In addition, passive immunization studies showed that specific antibodies of macaques immunized with rLcrV, rV10, or rF1, either alone or in combination, conferred protection against bubonic plague challenge in mice. Finally, we found that when we compared the reactivities of anti-rLcrV and anti-rV10 immune sera from cynomolgus macaques, BALB/c mice, and brown Norway rats with LcrV-derived peptides, rV10, but not rLcrV immune sera, lacked antibodies recognizing linear LcrV oligopeptides.

  18. Evaluation of early immune response-survival relationship in cynomolgus macaques after Anthrax Vaccine Adsorbed vaccination and Bacillus anthracis spore challenge.

    PubMed

    Sivko, G S; Stark, G V; Tordoff, K P; Taylor, K L; Glaze, E; VanRaden, M; Schiffer, J M; Hewitt, J A; Quinn, C P; Nuzum, E O

    2016-12-12

    Anthrax Vaccine Adsorbed (AVA, BioThrax) is approved by the US Food and Drug Administration for post-exposure prophylaxis (PEP) of anthrax in adults. The PEP schedule is 3 subcutaneous (SC) doses (0, 14 and 28 days), in conjunction with a 60 day course of antimicrobials. The objectives of this study were to understand the onset of protection from AVA PEP vaccination and to assess the potential for shortening the duration of antimicrobial treatment (http://www.phe.gov/Preparedness/mcm/phemce/Documents/2014-phemce-sip.pdf). We determined the efficacy against inhalation anthrax in nonhuman primates (NHP) of the first two doses of the PEP schedule by infectious challenge at the time scheduled for receipt of the third PEP dose (Day 28). Forty-eight cynomolgus macaques were randomized to five groups and vaccinated with serial dilutions of AVA on Days 0 and 14. NHP were exposed to Bacillus anthracis Ames spores on Day 28 (target dose 200 LD 50 equivalents). Anti-protective antigen (PA) IgG and toxin neutralizing antibody (TNA) responses to vaccination and in post-challenge survivors were determined. Post-challenge blood and selected tissue samples were assessed for B. anthracis at necropsy or end of study (Day 56). Pre-challenge humoral immune responses correlated with survival, which ranged from 24 to 100% survival depending on vaccination group. Surviving, vaccinated animals had elevated anti-PA IgG and TNA levels for the duration of the study, were abacteremic, exhibited no apparent signs of infection, and had no gross or microscopic lesions. However, survivors had residual spores in lung tissues. We conclude that the first two doses of the PEP schedule provide high levels of protection by the scheduled timing of the third dose. These data may also support consideration of a shorter duration PEP antimicrobial regimen. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The 17,18-epoxyeicosatetraenoic acid-G protein-coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques.

    PubMed

    Nagatake, Takahiro; Shiogama, Yumiko; Inoue, Asuka; Kikuta, Junichi; Honda, Tetsuya; Tiwari, Prabha; Kishi, Takayuki; Yanagisawa, Atsushi; Isobe, Yosuke; Matsumoto, Naomi; Shimojou, Michiko; Morimoto, Sakiko; Suzuki, Hidehiko; Hirata, So-Ichiro; Steneberg, Pär; Edlund, Helena; Aoki, Junken; Arita, Makoto; Kiyono, Hiroshi; Yasutomi, Yasuhiro; Ishii, Masaru; Kabashima, Kenji; Kunisawa, Jun

    2017-12-27

    Metabolites of eicosapentaenoic acid exert various physiologic actions. 17,18-Epoxyeicosatetraenoic acid (17,18-EpETE) is a recently identified new class of antiallergic and anti-inflammatory lipid metabolite of eicosapentaenoic acid, but its effects on skin inflammation and the underlying mechanisms remain to be investigated. We evaluated the effectiveness of 17,18-EpETE for control of contact hypersensitivity in mice and cynomolgus macaques. We further sought to reveal underlying mechanisms by identifying the responsible receptor and cellular target of 17,18-EpETE. Contact hypersensitivity was induced by topical application of 2,4-dinitrofluorobenzene. Skin inflammation and immune cell populations were analyzed by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. Neutrophil mobility was examined by means of imaging analysis in vivo and neutrophil culture in vitro. The receptor for 17,18-EpETE was identified by using the TGF-α shedding assay, and the receptor's involvement in the anti-inflammatory effects of 17,18-EpETE was examined by using KO mice and specific inhibitor treatment. We found that preventive or therapeutic treatment with 17,18-EpETE ameliorated contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques. 17,18-EpETE was recognized by G protein-coupled receptor (GPR) 40 (also known as free fatty acid receptor 1) and inhibited chemoattractant-induced Rac activation and pseudopod formation in neutrophils. Indeed, the antiallergic inflammatory effect of 17,18-EpETE was abolished in the absence or inhibition of GPR40. 17,18-EpETE inhibits neutrophil mobility through GPR40 activation, which is a potential therapeutic target to control allergic inflammatory diseases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys

    PubMed Central

    Reed, Steven G.; Coler, Rhea N.; Dalemans, Wilfried; Tan, Esterlina V.; DeLa Cruz, Eduardo C.; Basaraba, Randall J.; Orme, Ian M.; Skeiky, Yasir A. W.; Alderson, Mark R.; Cowgill, Karen D.; Prieels, Jean-Paul; Abalos, Rodolfo M.; Dubois, Marie-Claude; Cohen, Joe; Mettens, Pascal; Lobet, Yves

    2009-01-01

    The development of a vaccine for tuberculosis requires a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. We evaluated Mtb72F formulated in AS02A in the cynomolgus monkey model. The vaccine was immunogenic and caused no adverse reactions. When monkeys were immunized with bacillus Calmette–Guérin (BCG) and then boosted with Mtb72F in AS02A, protection superior to that afforded by using BCG alone was achieved, as measured by clinical parameters, pathology, and survival. We observed long-term survival and evidence of reversal of disease progression in monkeys immunized with the prime-boost regimen. Antigen-specific responses from protected monkeys receiving BCG and Mtb72F/AS02A had a distinctive cytokine profile characterized by an increased ratio between 3 Th1 cytokines, IFN-γ, TNF, and IL-2 and an innate cytokine, IL-6. To our knowledge, this is an initial report of a vaccine capable of inducing long-term protection against tuberculosis in a nonhuman primate model, as determined by protection against severe disease and death, and by other clinical and histopathological parameters. PMID:19188599

  1. Spring and summer survival of female mallards from northcentral Minnesota

    USGS Publications Warehouse

    Kirby, R.E.; Cowardin, L.M.

    1986-01-01

    Seasonal survival of 109 adult female mallards (Anas platyrhynchos) fitted with radio transmitters was evaluated in northcentral Minnesota during 1968-74. Survival rates for the 169-day breeding and postbreeding period were: 1.0 during nest initiation (36 days), 0.798 during incubation (28 days), 0.943 during brood rearing (51 days), 0.947 during molt (26 days), and 1.0 during premigration (28 days). Survival for the 169-day spring-summer period was 0.713 for adult females remaining on the study area. Fall-winter survival was estimated at 0.881 for those adult birds remaining on the study area throughout the summer. The data confirm speculation on relative risk to females of various phases of the mallard reproductive cycle and support previous conclusions that the northcentral Minnesota breeding mallard population is not self sustaining. The value of learning further details of processes affecting specific seasonal mortality factors for both adult and young waterfowl is emphasized.

  2. [Stimulation of D2-receptors improves passive avoidance learning in female rats].

    PubMed

    Fedotova, Iu O

    2012-01-01

    The involvement of D2-receptors in learning/memory processes during ovary cycle was assessed in the adult female rats. Quinperole (0,1 mg/kg, i.p.), D2-receptor agonist and sulpiride (10,0 mg/kg, i.p.), D2-receptor antagonist were injected chronically to adult female rats. Learning of these animals was assessed in different models: passive avoidance performance and Morris water maze. Chronic quinperole administration to females resulted in the appearance of the passive avoidance performance in proestrous and estrous, as distinct from the control animals. Also, quinperole improved spatial learning in proestrous and stimulated it in estrous in Morris water maze. Chronic sulpiride administration similarly impaired non-spatial and spatial learning in females during all phases of ovary cycle. The results of the study suggest modulating role of D2-receptors in learning/memory processes during ovary cycle in the adult female rats.

  3. Influencers and preference predictors of HPV vaccine uptake among US male and female young adult college students.

    PubMed

    LaJoie, A Scott; Kerr, Jelani C; Clover, Richard D; Harper, Diane M

    2018-06-01

    The purpose of the study was to assess the knowledge, attitudes and beliefs of male and female college students in Kentucky about HPV associated diseases and vaccines, and to determine which parameters predicted self-reported uptake of HPV vaccination. A self-selected cross-sectional sample of college students completed an evidence-based online survey. Of approximately 1200 potential respondents, 585 completed the survey. The average age was 20.6 (SD 3.15) and 78% were female; 84% of the population had had one or more sexual partners. Concern for HPV vaccine safety and potential need for boosters did not significantly deter vaccine uptake. Likewise, knowledge about HPV associated cancers was not predictive of vaccine uptake. On the other hand, parental influence for vaccination was a strong predictor for vaccine uptake (aOR = 5.32, 2.71-13.03), and free vaccine nearly doubled the likelihood of being vaccinated (aOR 1.90, 1.05-3.41). In addition, the strong preference for the respondent's partner to be HPV vaccinated predicted vaccine uptake (aOR = 4.04, 95% CI: 2.31-7.05), but the lack of preference for partner vaccination predicted an unvaccinated self (aOR = 0.50, 0.27-0.93). HPV vaccination has been successful in young adult college students in Kentucky. Young adults prefer their partners to be HPV vaccinated regardless of whether they themselves are vaccinated. Parental influence and free vaccine were positive predictors for vaccine uptake in this population. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Systemic Gene Delivery Transduces the Enteric Nervous System of Guinea Pigs and Cynomolgus Macaques

    PubMed Central

    Gombash, Sara E; Cowley, Christopher J; Fitzgerald, Julie A; Lepak, Christina A; Neides, Mitchell G; Hook, Kathryn; Todd, Levi J; Wang, Guo-Du; Mueller, Christian; Kaspar, Brian K; Bielefeld, Eric C; Fischer, Andrew J; Wood, Jackie D; Foust, Kevin D

    2017-01-01

    Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or PBS. Piglets were euthanized three weeks post-injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9 treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders. PMID:28771235

  5. Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

    PubMed

    Gombash, S E; Cowley, C J; Fitzgerald, J A; Lepak, C A; Neides, M G; Hook, K; Todd, L J; Wang, G-D; Mueller, C; Kaspar, B K; Bielefeld, E C; Fischer, A J; Wood, J D; Foust, K D

    2017-10-01

    Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline. Piglets were euthanized three weeks post injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP-positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9-treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders.

  6. Biodistribution and safety of a live attenuated tetravalent dengue vaccine in the cynomolgus monkey.

    PubMed

    Ravel, Guillaume; Mantel, Nathalie; Silvano, Jeremy; Rogue, Alexandra; Guy, Bruno; Jackson, Nicholas; Burdin, Nicolas

    2017-10-13

    The first licensed dengue vaccine is a recombinant, live, attenuated, tetravalent dengue virus vaccine (CYD-TDV; Sanofi Pasteur). This study assessed the biodistribution, shedding, and toxicity of CYD-TDV in a non-human primate model as part of the nonclinical safety assessment program for the vaccine. Cynomolgus monkeys were given one subcutaneous injection of either one human dose (5log 10 CCID 50 /serotype) of CYD-TDV or saline control. Study endpoints included clinical observations, body temperature, body weight, food consumption, clinical pathology, immunogenicity, and post-mortem examinations including histopathology. Viral load, distribution, persistence, and shedding in tissues and body fluids were evaluated by quantitative reverse transcriptase polymerase chain reaction. The subcutaneous administration of CYD-TDV was well tolerated. There were no toxicological findings other than expected minor local reactions at the injection site. A transient low level of CYD-TDV viral RNA was detected in blood and the viral genome was identified primarily at the injection site and in the draining lymph nodes following immunization. These results, together with other data from repeat-dose toxicity and neurovirulence studies, confirm the absence of toxicological concern with CYD-TDV and corroborate clinical study observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Neuroendocrine Consequences of Androgen Excess in Female Rodents

    PubMed Central

    Foecking, Eileen M.; McDevitt, Melissa A.; Acosta-Martínez, Maricedes; Horton, Teresa H.; Levine, Jon E.

    2008-01-01

    Androgens exert significant organizational and activational effects on the nervous system and behavior. Despite the fact that female mammals generally produce low levels of androgens, relative to the male of the same species, increasing evidence suggests that androgens can exert profound effects on the normal physiology and behavior of females during fetal, neonatal, and adult stages of life. This review examines the effects of exposure to androgens at three stages of development – as an adult, during early postnatal life and as a fetus, on reproductive hormone secretions in female rats. We examine the effects of androgen exposure both as a model of neuroendocrine sexual differentiation and with respect to the role androgens play in the normal female. We then discuss the hypothesis that androgens may cause epigenetic modification of estrogen target genes in the brain. Finally we consider the clinical consequences of excess androgen exposure in women. PMID:18374922

  8. Survival of adult female northern pintails in Sacramento Valley, California

    USGS Publications Warehouse

    Miller, Michael R.; Fleskes, Joseph P.; Orthmeyer, Dennis L.; Newton, Wesley E.; Gilmer, David S.

    1995-01-01

    North American populations of northern pintails (Anas acuta) declined between 1979 and the early 1990s. To determine if low survival during winter contributed to declines, we estimated winter (last week of Aug-Feb 1987-90) survival for 190 adult (after hatching yr [AHY]) female radio-tagged pintails in late summer in Sacramento Valley (SACV), California. Survival rates did not vary by winter (P = 0.808), among preseason, hunting season, or postseason intervals (P = 0.579), or by body mass at time of capture (P = 0.127). Premolt (wing) pintails (n = 10) tended to survive at a lower rate (0.622, SE = 0.178) than pintails that had already replaced flight feathers (0.887, SE = 0.030) (P = 0.091). The pooled survival (all years) estimate for the 180-day winter was 0.874 (SE = 0.031). Hunting mortality rate (0.041-0.087) and nonhunting mortality rate (0.013-0.076) did not differ among years (P = 0.332) or within years (all P > 0.149). Legal hunting (n = 7), predation (n = 4), cholera (n = 2), illegal shooting (n = 2), botulism (n = 1), and unknown cause (n = 1) accounted for all mortality. Nonwintering survival (annu. survival/winter survival = 0.748) was lower than winter survival; thus, if gains in annual survival are desired for this population, managers should first examine the breeding-migration period for opportunities to achieve increases.

  9. The effect of calabash chalk on some hematological parameters in female adult Wistar rats.

    PubMed

    Akpantah, Amabe Otoabasi; Ibok, Ofon Samuel; Ekong, Moses Bassey; Eluwa, Mokutima Amarachi; Ekanem, Theresa Bassey

    2010-09-05

    Calabash chalk is a naturally occurring mineral consumed among the Nigerian community for pleasure and commonly by pregnant women as a remedy for morning sickness. Reports have shown that it contains different toxic substances, with lead being the most abundant. This study was therefore undertaken to ascertain the effect of two commonly available preparations of this chalk on some hematological parameters. Twenty-four adult female Wistar rats with average weight of 100 g were assigned into three groups (1, 2, 3). Group 1 served as the control and the animals received distilled water, while Groups 2 and 3 were treated by oral gavage with 40 mg/kg of non-salted (NSCC) and salted calabash chalk (SCC), respectively, for 14 days. The hemoglobin (Hb) concentration and red blood cell (RBC) count were significantly (p<0.05, 0.001 respectively) lower in the NSCC group, while erythrocyte sedimentation rate (ESR) was significantly (p<0.05) higher in the NSCC group compared to the control. There were no significant differences in packed cell volume (PCV), white blood cell (WBC) and platelet (Pl) counts compared to the control. The SCC group presented no significant difference in all blood count parameters compared to the control. This infers that calabash chalk, particularly the non-salted form, alters the normal concentration of Hb, RBC and Pl counts, and ESR, as observed in the female Wistar rats studied.

  10. Intermittent pair-housing, pair relationship qualities, and HPA activity in adult female rhesus macaques.

    PubMed

    Hannibal, Darcy L; Cassidy, Lauren C; Vandeleest, Jessica; Semple, Stuart; Barnard, Allison; Chun, Katie; Winkler, Sasha; McCowan, Brenda

    2018-05-02

    Laboratory rhesus macaques are often housed in pairs and may be temporarily or permanently separated for research, health, or management reasons. While both long-term social separations and introductions can stimulate a stress response that impacts inflammation and immune function, the effects of short-term overnight separations and whether qualities of the pair relationship mediate these effects are unknown. In this study, we investigated the effects of overnight separations on the urinary cortisol concentration of 20 differentially paired adult female rhesus macaques (Macaca mulatta) at the California National Primate Research Center. These females were initially kept in either continuous (no overnight separation) or intermittent (with overnight separation) pair-housing and then switched to the alternate pair-housing condition part way through the study. Each study subject was observed for 5 weeks, during which we collected measures of affiliative, aggressive, anxious, abnormal, and activity-state behaviors in both pair-housing conditions. Additionally, up to three urine samples were collected from each subject per week and assayed for urinary free cortisol and creatinine. Lastly, the behavioral observer scored each pair on four relationship quality attributes ("Anxious," "Tense," "Well-meshed," and "Friendly") using a seven-point scale. Data were analyzed using a generalized linear model with gamma distribution and an information theoretic approach to determine the best model set. An interaction between the intermittent pairing condition and tense pair adjective rating was in the top three models of the best model set. Dominance and rates of affiliation were also important for explaining urinary cortisol variation. Our results suggest that to prevent significant changes in HPA-axis activation in rhesus macaque females, which could have unintended effects on research outcomes, pairs with "Tense" relationships and overnight separations preventing tactile contact

  11. Developmental Environment Effects on Sexual Selection in Male and Female Drosophila melanogaster

    PubMed Central

    Morimoto, Juliano; Pizzari, Tommaso; Wigby, Stuart

    2016-01-01

    The developmental environment can potentially alter the adult social environment and influence traits targeted by sexual selection such as body size. In this study, we manipulated larval density in male and female Drosophila melanogaster, which results in distinct adult size phenotypes–high (low) densities for small (large) adults–and measured sexual selection in experimental groups consisting of adult males and females from high, low, or a mixture of low and high larval densities. Overall, large adult females (those reared at low larval density) had more matings, more mates and produced more offspring than small females (those reared at high larval density). The number of offspring produced by females was positively associated with their number of mates (i.e. there was a positive female Bateman gradient) in social groups where female size was experimentally varied, likely due to the covariance between female productivity and mating rate. For males, we found evidence that the larval environment affected the relative importance of sexual selection via mate number (Bateman gradients), mate productivity, paternity share, and their covariances. Mate number and mate productivity were significantly reduced for small males in social environments where males were of mixed sizes, versus social environments where all males were small, suggesting that social heterogeneity altered selection on this subset of males. Males are commonly assumed to benefit from mating with large females, but in contrast to expectations we found that in groups where both the male and female size varied, males did not gain more offspring per mating with large females. Collectively, our results indicate sex-specific effects of the developmental environment on the operation of sexual selection, via both the phenotype of individuals, and the phenotype of their competitors and mates. PMID:27167120

  12. Developments of sulcal pattern and subcortical structures of the forebrain in cynomolgus monkey fetuses: 7-tesla magnetic resonance imaging provides high reproducibility of gross structural changes.

    PubMed

    Sawada, Kazuhiko; Sun, Xue-Zhi; Fukunishi, Katsuhiro; Kashima, Masatoshi; Sakata-Haga, Hiromi; Tokado, Hiroshi; Aoki, Ichio; Fukui, Yoshihiro

    2009-09-01

    The aim of this study was to spatio-temporally clarify gross structural changes in the forebrain of cynomolgus monkey fetuses using 7-tesla magnetic resonance imaging (MRI). T(1)-weighted coronal, horizontal, and sagittal MR slices of fixed left cerebral hemispheres were obtained from one male fetus at embryonic days (EDs) 70-150. The timetable for fetal sulcation by MRI was in good agreement with that by gross observations, with a lag time of 10-30 days. A difference in detectability of some sulci seemed to be associated with the length, depth, width, and location of the sulci. Furthermore, MRI clarified the embryonic days of the emergence of the callosal (ED 70) and circular (ED 90) sulci, which remained unpredictable under gross observations. Also made visible by the present MRI were subcortical structures of the forebrain such as the caudate nucleus, globus pallidus, putamen, major subdivisions of the thalamus, and hippocampal formation. Their adult-like features were formed by ED 100, corresponding to the onset of a signal enhancement in the gray matter, which reflects neuronal maturation. The results reveal a highly reproducible level of gross structural changes in the forebrain using a high spatial 7-tesla MRI. The present MRI study clarified some changes that are difficult to demonstrate nondestructively using only gross observations, for example, the development of cerebral sulci located on the deep portions of the cortex, as well as cortical and subcortical neuronal maturation.

  13. Female-to-male transmasculine adult health: a mixed-methods community-based needs assessment.

    PubMed

    Reisner, Sari L; Gamarel, Kristi E; Dunham, Emilia; Hopwood, Ruben; Hwahng, Sel

    2013-01-01

    There is a dearth of health research about transgender people. This mixed-methods study sought to formatively investigate the health and perceived health needs of female-to-male transmasculine adults. A cross-sectional quantitative needs assessment (n = 73) and qualitative open-ended input (n = 19) were conducted in June 2011. A latent class analysis modeled six binary health indicators (depression, alcohol use, current smoking, asthma, physical inactivity, overweight status) to identify clusters of presenting health issues. Four clusters of health indicators emerged: (a) depression; (b) syndemic (all indicators); (c) alcohol use, overweight status; and (d) smoking, physical inactivity, overweight status. Transphobic discrimination in health care and avoiding care were each associated with membership in the syndemic class. Qualitative themes included personal health care needs, community needs, and resilience and protective factors. Findings fill an important gap about the health of transmasculine communities, including the need for public health efforts that holistically address concomitant health concerns.

  14. Acute exposure to gas-supersaturated water does not affect reproductive success of female adult chinook salmon late in maturation

    USGS Publications Warehouse

    Gale, William L.; Maule, A.G.; Postera, A.; Peters, M.H.

    2004-01-01

    At times, total dissolved gas concentrations in the Columbia and Snake rivers have been elevated due to involuntary spill from high spring runoff and voluntary spill used as a method to pass juvenile salmonids over dams. The goal of this project was to determine if acute exposure to total dissolved gas supersaturation (TDGS) affects the reproductive performance of female chinook salmon late in their maturation. During this study, adult female spring chinook salmon were exposed to mean TDGS levels of 114.1 % to 125.5%. We ended exposures at first mortality, or at the appearance of impending death. Based on this criterion, exposures lasted from 10 to 68 h and were inversely related to TDGS. There was no effect of TDGS on pre-spawning mortality or fecundity when comparing treatment fish to experimental controls or the general hatchery population four to six weeks after exposures. Egg quality, based on egg weight and egg diameter, did not differ between treatment and control fish. Fertilization rate and survival to eyed-stage was high (>94%) for all groups. With the exception of Renibacterium salmoninarum (the causative agent of bacterial kidney disease; BKD), no viral or bacterial fish pathogens were isolated from experimental fish. The prevalence (about 45%) and severity of R. salmoninarum did not differ among the groups or the general hatchery population. We conclude that these acute exposures to moderate levels of gas-supersaturated water-perhaps similar to that experienced by immigrating adult salmon as they approach and pass a hydropower dam on the Columbia River-did not affect reproductive success of female chinook salmon late in their maturation. These results are most applicable to summer and fall chinook salmon, which migrate in the summer/fall and spawn shortly after reaching their natal streams. Published in 2004 by John Wiley and Sons, Ltd.

  15. Do gravid female Anolis nebulosus thermoregulate differently than males and non-gravid females?

    PubMed

    Woolrich-Piña, Guillermo A; Smith, Geoffrey R; Lemos-Espinal, Julio A; Ramírez-Silva, Juan Pablo

    2015-08-01

    In lizards, the role of gravid oviparous females in controlling the temperature experienced by developing embryos prior to oviposition has been rarely examined. In particular, relatively little is known about the effect of gravidity on the thermal ecology of female Anolis lizards. Here we examine the thermal ecology of Anolis nebulosus from Nayarit, Mexico, with a particular goal of comparing the thermal ecology of gravid females to that of non-gravid females and males. The thermal efficiency (E) of gravid female A. nebulosus (E=0.782) was higher than in males (E=0.464), and to a lesser extent, non-gravid females (E=0.637), despite no significant differences observed in body, air, operative, or set point temperatures among males, gravid females, and non-gravid females. Gravid females had smaller differences between body temperatures and set point temperatures (db), but did not differ in the difference between operative temperature and set point temperature (de). Gravid females used sun-shade and shaded microhabitats proportionately more than males and non-gravid females, and rarely used sunny microhabitats. Our results suggest that gravid A. nebulosus are using a different and more efficient thermoregulatory strategy than other adults in the population. Such efficient thermoregulation is possibly related to females attempting to provide a thermal environment that is conducive to the development of embryos in eggs prior to oviposition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Does education matter? Examining racial differences in the association between education and STI diagnosis among black and white young adult females in the U.S.

    PubMed

    Annang, Lucy; Walsemann, Katrina M; Maitra, Debeshi; Kerr, Jelani C

    2010-01-01

    Education has long been considered a protective factor against sexual risk behaviors and sexually transmitted infections (STIs) among adolescents; however, few have explored this association and determined differences across racial/ethnic groups of young adult females on a national scale. The purpose of this study was to (1) describe the association between education and STI diagnosis among a national sample of black and white young adult females and (2) examine racial differences in this association. We used data from the National Longitudinal Study of Adolescent Health (Add Health) to assess the association between education and chlamydia, gonorrhea, and/or trichomoniasis (self-reported and assay-diagnosed) in 2001-2002 using logistic regression analysis. After adjustment for risk behaviors, education was inversely associated with any assay-diagnosed STI, but this association was nonsignificant among black women for self-reported STI. Additionally, black females enrolled in, or who graduated from, college had significantly higher predicted probabilities of having an STI (12.4% self-reported; 13.4% assay-diagnosed) compared with white females who had less than a high school diploma (6.4% self-reported; 2.3% assay-diagnosed). Educational status was not uniformly protective against STIs for black and white females in this sample. Particularly for young black women, other factors may play a more prominent role in determining STI risk. Social determinants, such as education, should be viewed as important factors associated with STI prevalence, but their differential impact on various racial/ethnic groups should also be considered when addressing the disproportionate rates of STIs in the U.S.

  17. Differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

    PubMed

    Tong, Ling-Ling; Ding, You-Quan; Jing, Hong-Bo; Li, Xuan-Yang; Qi, Jian-Guo

    2015-05-06

    Peripheral nerve functional recovery after injuries relies on both axon regeneration and remyelination. Both axon regeneration and remyelination require intimate interactions between regenerating neurons and their accompanying Schwann cells. Previous studies have shown that motor and sensory neurons are intrinsically different in their regeneration potentials. Moreover, denervated Schwann cells accompanying myelinated motor and sensory axons have distinct gene expression profiles for regeneration-associated growth factors. However, it is unknown whether differential motor and sensory functional recovery exists. If so, the particular one among axon regeneration and remyelination responsible for this difference remains unclear. Here, we aimed to establish an adult rat sciatic nerve crush model with the nonserrated microneedle holders and measured rat motor and sensory functions during regeneration. Furthermore, axon regeneration and remyelination was evaluated by morphometric analysis of electron microscopic images on the basis of nerve fiber classification. Our results showed that Aα fiber-mediated motor function was successfully recovered in both male and female rats. Aδ fiber-mediated sensory function was partially restored in male rats, but completely recovered in female littermates. For both male and female rats, the numbers of regenerated motor and sensory axons were quite comparable. However, remyelination was diverse among myelinated motor and sensory nerve fibers. In detail, Aβ and Aδ fibers incompletely remyelinated in male, but not female rats, whereas Aα fibers fully remyelinated in both sexes. Our result indicated that differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

  18. Magical Thinking in Formal Operational Adults.

    ERIC Educational Resources Information Center

    Lesser, R.; Paisner, M.

    1985-01-01

    Female adult members of a spiritual community denying the existence of chance were matched by age and educational level with adult female nonmembers. Level of development of logical operations and causal belief systems were assessed. Findings indicate that personally charged, magical concepts of causality can develop into maturity and exist…

  19. Studies of young female responses to acute ozone exposure. Final report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Adams, W.C.

    The primary purposes of this research were to determine if: (1) young adult females respond with greater acute effects of ozone (O3) than their male counterparts at a dose relative to lung size as well as at the same total dose; (2) O3 response in females is influenced by the disparate levels of progesterone (a steroid hormone) that they experience during the various phases of their menstrual cycles; and (3) O3 exposure has an effect on the integrity of normal menstrual cycles of healthy young adult females.

  20. A comparative study of the effect of diet and soda carbonated drinks on the histology of the cerebellum of adult female albino Wistar rats.

    PubMed

    Eluwa, M A; Inyangmme, I I; Akpantah, A O; Ekanem, T B; Ekong, M B; Asuquo, O R; Nwakanma, A A

    2013-09-01

    Carbonated drinks are widely consumed because of their taste and their ability to refresh and quench thirst. These carbonated drinks also exist in the form of diet drinks, for example Diet Coke®, Pepsi®, extra. A comparative effect of the diet and regular soda carbonated drinks on the histology of the cerebellum of female albino Wistar rats was investigated. Fifteen adult female Wistar rats weighing between 180-200 g were divided into 3 groups; designated as groups A, B and C, and each group consisted of five rats. Group A was the Control group and received distilled water, while groups B and C were the experimental groups. Group B was administered 50 ml of regular soda (RS), and group C was administered 50 ml of diet soda (DS) each per day for 21 days, and the rats were sacrificed on Day 22, and their cerebellums excised and preserved. Histological result of the sections of the cerebellum showed shrunken and degenerated Purkinje cells with hypertrophied dendrites, especially in the DS group, which was less in the RS group compared to the control group. These results suggest that diet soda has adverse effect on the cerebellum of adult female albino Wistar rats.

  1. Relative Heights of Males and Females in Children's Drawings.

    ERIC Educational Resources Information Center

    Cox, Maureen V.; Wright, Rebekah

    2000-01-01

    Examined in two studies the height of male and female figures in 5- and 7-year-olds' drawings. Found that adult figures were drawn taller than child figures. For boys, mean male and female heights were approximately the same. Girls drew females taller than males because more girls used different structures such as incorporating a skirt or trousers…

  2. Cognition in Males and Females with Autism: Similarities and Differences

    PubMed Central

    Lai, Meng-Chuan; Lombardo, Michael V.; Ruigrok, Amber N. V.; Chakrabarti, Bhismadev; Wheelwright, Sally J.; Auyeung, Bonnie; Allison, Carrie; Baron-Cohen, Simon

    2012-01-01

    The male bias in autism spectrum conditions (ASC) has led to females with ASC being under-researched. This lack of attention to females could hide variability due to sex that may explain some of the heterogeneity within ASC. In this study we investigate four key cognitive domains (mentalizing and emotion perception, executive function, perceptual attention to detail, and motor function) in ASC, to test for similarities and differences between males and females with and without ASC (n = 128 adults; n = 32 per group). In the mentalizing and facial emotion perception domain, males and females with ASC showed similar deficits compared to neurotypical controls. However, in attention to detail and dexterity involving executive function, although males with ASC showed poorer performance relative to neurotypical males, females with ASC performed comparably to neurotypical females. We conclude that performance in the social-cognitive domain is equally impaired in male and female adults with ASC. However, in specific non-social cognitive domains, performance within ASC depends on sex. This suggests that in specific domains, cognitive profiles in ASC are modulated by sex. PMID:23094036

  3. Ontogeny of cocaine-induced behaviors and cocaine pharmacokinetics in male and female neonatal, preweanling, and adult rats.

    PubMed

    McDougall, Sanders A; Apodaca, Matthew G; Mohd-Yusof, Alena; Mendez, Adrian D; Katz, Caitlin G; Teran, Angie; Garcia-Carachure, Israel; Quiroz, Anthony T; Crawford, Cynthia A

    2018-04-18

    Ontogenetic differences in the behavioral responsiveness to cocaine have often been attributed to the maturation of dopaminergic elements (e.g., dopamine transporters, D2 High receptors, receptor coupling, etc.). The purpose of this study was to determine whether ontogenetic changes in cocaine pharmacokinetics might contribute to age-dependent differences in behavioral responsiveness. Male and female neonatal (PD 5), preweanling (PD 10 and PD 20), and adult (PD 70) rats were injected (IP) with cocaine or saline and various behaviors (e.g., locomotor activity, forelimb paddle, vertical activity, head-down sniffing, etc.) were measured for 90 min. In a separate experiment, the dorsal striata of young and adult rats were removed at 10 time points (0-210 min) after IP cocaine administration. Peak cocaine values, cocaine half-life, and dopamine levels were determined using HPLC. When converted to percent of saline controls, PD 5 and PD 10 rats were generally more sensitive to cocaine than older rats, but this effect varied according to the behavior being assessed. Peak cocaine values did not differ according to age or sex, but cocaine half-life in brain was approximately 2 times longer in PD 5 and PD 10 rats than adults. Cocaine pharmacokinetics did not differ between PD 20 and PD 70 rats. Differences in the cocaine-induced behavioral responsiveness of very young rats (PD 5 and PD 10) and adults may be attributable, at least in part, to pharmacokinetic factors; whereas, age-dependent behavioral differences between the late preweanling period and adulthood cannot readily be ascribed to cocaine pharmacokinetics.

  4. The Role of Lexical Stress on the Use of Vocal Fry in Young Adult Female Speakers.

    PubMed

    Gibson, Todd A

    2017-01-01

    Vocal fry is a voice register often used by young adult women for sociolinguistic purposes. Some acoustic correlates of lexical stress, however, appear incompatible with the use of vocal fry. The objective of this study was to systematically examine the role of lexical stress in the use of vocal fry by young adult women. This is a semi-randomized controlled laboratory study. Fifty female undergraduate students were recorded repeating one-, two-, three-, and four-syllable nonwords that conformed to English phonotactics. Nonwords were presented in order from shorter to longer lengths, with stimuli randomized within syllable length. Perceptual analyses of recordings were augmented by acoustic analyses to identify each syllable in which vocal fry occurred. Eighty-six percent of participants produced at least one episode of vocal fry. Vocal fry was more likely to occur in unstressed than stressed position, and the likelihood increased as distance from the stressed syllable increased. There was considerable variability in the use of vocal fry. Frequent and infrequent users varied on the degree to which they used vocal fry in single-syllable nonwords. Vocal fry use persists among young adult women even in the absence of syntactic and pragmatic influences. Lexical stress appeared to dramatically reduce the use of vocal fry. Patterns of vocal fry use appeared to be different for frequent and infrequent users of this vocal register. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  5. Neuroanatomical Relationship of nNOS to GnRH and Kisspeptin Neurons in Adult Female Sheep and Primates.

    PubMed

    Bedenbaugh, Michelle; McCosh, Rick; Lopez, Justin; Connors, John; Goodman, Robert L; Hileman, Stan

    2018-06-21


    Background: Neuronal intermediates that communicate estrogen and progesterone feedback to gonadotropin-releasing hormone (GnRH) neurons are essential for modulating reproductive cyclicity. Individually, kisspeptin and nitric oxide (NO) influence GnRH secretion. However, it is possible these two neuronal intermediates interact with one another to affect reproductive cyclicity. We investigated the neuroanatomical relationship of one isoform of the enzyme that synthesizes NO, neuronal nitric oxide synthase (nNOS), to kisspeptin and GnRH in adult female rhesus monkeys and sheep using dual-label immunofluorescence. Additionally, we evaluated if the phase of the reproductive cycle would affect these relationships. Overall, no effect of stage of cycle was observed for any variable in this study. In the arcuate nucleus (ARC) of sheep, 98.8±3.5% of kisspeptin neurons colocalized with nNOS, and kisspeptin close-contacts were observed onto nNOS neurons. In contrast to ewes, no colocalization was observed between kisspeptin and nNOS in the infundibular arcuate nucleus (INF ARC) of primates, but kisspeptin fibers were apposed to nNOS neurons. In the preoptic area (POA) of ewes, 15.0±4.2% of GnRH neurons colocalized with nNOS. In primates, 38.8±10.1% of GnRH neurons in the mediobasal hypothalamus (MBH) colocalized with nNOS, and GnRH close-contacts were observed onto nNOS neurons in both sheep and primates. Although species differences were observed, this work establishes a neuroanatomical framework between nNOS and kisspeptin and nNOS and GnRH in adult female nonhuman primates and sheep.
    . ©2018S. Karger AG, Basel.

  6. Chronic Ketamine Exposure Causes White Matter Microstructural Abnormalities in Adolescent Cynomolgus Monkeys.

    PubMed

    Li, Qi; Shi, Lin; Lu, Gang; Yu, Hong-Luan; Yeung, Fu-Ki; Wong, Nai-Kei; Sun, Lin; Liu, Kai; Yew, David; Pan, Fang; Wang, De-Feng; Sham, Pak C

    2017-01-01

    Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia. Thus, the present study aimed to expand on previous investigations by examining causal effects of repeated ketamine exposure on white matter integrity in a non-human primate model. Ketamine or saline (control) was administered intravenously for 3 months to male adolescent cynomolgus monkeys ( n = 5/group). Diffusion tensor imaging (DTI) experiments were performed and tract-based spatial statistics (TBSS) was used for data analysis. Fractional anisotropy (FA) was quantified across the whole brain. Profoundly reduced FA on the right side of sagittal striatum, posterior thalamic radiation (PTR), retrolenticular limb of the internal capsule (RLIC) and superior longitudinal fasciculus (SLF), and on the left side of PTR, middle temporal gyrus and inferior frontal gyrus were observed in the ketamine group compared to controls. Diminished white matter integrity found in either fronto-thalamo-temporal or striato-thalamic connections with tracts including the SLF, PTR, and RLIC lends support to similar findings from DTI studies on schizophrenia in humans. This study suggests that chronic ketamine exposure is a useful pharmacological paradigm that might provide translational insights into the pathophysiology and treatment of schizophrenia.

  7. Social affiliation matters: both same-sex and opposite-sex relationships predict survival in wild female baboons

    PubMed Central

    Archie, Elizabeth A.; Tung, Jenny; Clark, Michael; Altmann, Jeanne; Alberts, Susan C.

    2014-01-01

    Social integration and support can have profound effects on human survival. The extent of this phenomenon in non-human animals is largely unknown, but such knowledge is important to understanding the evolution of both lifespan and sociality. Here, we report evidence that levels of affiliative social behaviour (i.e. ‘social connectedness’) with both same-sex and opposite-sex conspecifics predict adult survival in wild female baboons. In the Amboseli ecosystem in Kenya, adult female baboons that were socially connected to either adult males or adult females lived longer than females who were socially isolated from both sexes—females with strong connectedness to individuals of both sexes lived the longest. Female social connectedness to males was predicted by high dominance rank, indicating that males are a limited resource for females, and females compete for access to male social partners. To date, only a handful of animal studies have found that social relationships may affect survival. This study extends those findings by examining relationships to both sexes in by far the largest dataset yet examined for any animal. Our results support the idea that social effects on survival are evolutionarily conserved in social mammals. PMID:25209936

  8. When an adult female seeks ritual genital alteration: ethics, law, and the parameters of participation.

    PubMed

    Cantor, Julie D

    2006-04-01

    Ritual genital cutting for women, a common practice in Africa and elsewhere around the world, remains dangerous and controversial. In recent years, a 14-year-old girl living in Sierra Leone exsanguinated and died following a ritualistic genital cutting. Hoping to avoid that fate, women with backgrounds that accept ritual genital cutting may, when they reach majority age, ask plastic surgeons to perform genital alterations for cultural reasons. Although plastic surgeons routinely perform cosmetic procedures, unique ethical and legal concerns arise when an adult female patient asks a surgeon to spare her the tribal elder's knife and alter her genitalia according to tradition and custom. Misinformation and confusion about this issue exist. This article explores the ethical and legal issues relevant to this situation and explains how the thoughtful surgeon should proceed.

  9. The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats.

    PubMed

    Svensson, J; Lall, S; Dickson, S L; Bengtsson, B A; Rømer, J; Ahnfelt-Rønne, I; Ohlsson, C; Jansson, J O

    2000-06-01

    Growth hormone (GH) is of importance for normal bone remodelling. A recent clinical study demonstrated that MK-677, a member of a class of GH secretagogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investigate whether the GHSs, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6), increase bone mineral content (BMC) in young adult female rats. Thirteen-week-old female Sprague-Dawley rats were given IPA (0.5 mg/kg per day; n=7), GHRP-6 (0.5 mg/kg per day; n=8), GH (3.5 mg/kg per day; n=7), or vehicle administered continuously s.c. via osmotic minipumps for 12 weeks. The animals were followed in vivo by dual X-ray absorptiometry (DXA) measurements every 4th week. After the animals were killed, femurs were analysed in vitro by mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. After this, excised femurs and vertebrae L6 were analysed by the use of Archimedes' principle and by determinations of ash weights. All treatments increased body weight and total tibial and vertebral BMC measured by DXA in vivo compared with vehicle-treated controls. However, total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vitro revealed that the increase in the cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged. Femur and vertebra L6 volumes were increased but no effect was seen on the volumetric BMDs as measured by Archimedes' principle. Ash weight was increased by all treatments, but the mineral concentration was unchanged. We conclude that treatment of adult female rats with the GHSs ipamorelin and GHRP-6 increases BMC as measured by DXA in vivo. The results of in vitro measurements using pQCT and Archimedes' principle, in

  10. Sibling Relationships Cognition in Japanese Female University Students

    ERIC Educational Resources Information Center

    Sawai, Misae; Kato, Daiki

    2017-01-01

    This study examined the factor structure of sibling relationships in Japanese female university students. Two hundred and fifteen Japanese female university students participated in this study. The Adult Sibling Relationship Scale (ASRQ, Stocker et al., 1997) was used to measure sibling relationship cognition. The model was constructed as a result…

  11. Effects of strength training, detraining and retraining in muscle strength, hypertrophy and functional tasks in older female adults.

    PubMed

    Correa, Cleiton S; Cunha, Giovani; Marques, Nise; Oliveira-Reischak, Ãlvaro; Pinto, Ronei

    2016-07-01

    Previous studies presented different results regarding the maintenance time of muscular adaptations after strength training and the ability to resume the gains on muscular performance after resumption of the training programme. This study aimed to verify the effect of strength training on knee extensors and elbow flexor muscle strength, rectus femoris muscle volume and functional performance in older female adults after 12 weeks of strength training, 1 year of detraining and followed by 12 weeks of retraining. Twelve sedentary older women performed 12 weeks of strength training, 1 year of detraining and 12 weeks of retraining. The strength training was performed twice a week, and the assessment was made four times: at the baseline, after the strength training, after the detraining and after the retraining. The knee extensor and elbow flexor strength, rectus femoris muscle volume and functional task were assessed. Strength of knee extensor and elbow flexor muscles, rectus femoris muscle volume and 30-s sit-to-stand increased from baseline to post-training (respectively, 40%, 70%, 38% and 46%), decreased after detraining (respectively, -36%, -64%, -35% and -43%) and increased again these parameters after retraining (35%, 68%, 36% and 42%). Strength training induces gains on strength and hypertrophy, also increased the performance on functional tasks after the strength training. The stoppage of the strength caused strength loss and reduction of functional performance. The resumption of the strength training promoted the same gains of muscular performance in older female adults. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  12. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges.

    PubMed

    Grant-Klein, Rebecca J; Altamura, Louis A; Badger, Catherine V; Bounds, Callie E; Van Deusen, Nicole M; Kwilas, Steven A; Vu, Hong A; Warfield, Kelly L; Hooper, Jay W; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2015-01-01

    Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA plasmids expressing codon-optimized glycoprotein (GP) genes of Ebola virus (EBOV) or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual vaccines elicited slightly higher IgG responses to EBOV or MARV than did the combination vaccines. No significant differences in immune responses of macaques given the individual or combination vaccines were measured by pseudovirion neutralization or IFN-γ ELISpot assays. Both the MARV and mixed vaccines were able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a greater proportion of macaques vaccinated with the EBOV vaccine survived lethal EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs. 1/6). EBOV challenge survivors had significantly higher pre-challenge neutralizing antibody titers than those that succumbed.

  13. Effect of puberty on coronary arteries from female pigs.

    PubMed

    Chatrath, Ritu; Ronningen, Karen L; LaBreche, Peter; Severson, Sandra R; Jayachandran, Muthuvel; Bracamonte, Margarita P; Miller, Virginia M

    2003-10-01

    Vascular function changes following loss of ovarian hormones in women at menopause and in experimental animals following surgical ovariectomy. Little is known about changes in vascular function during hormonal transition from sexual immaturity (juvenile) to sexual maturity. Therefore, experiments were designed to determine effects of natural puberty on vascular function in female pigs. Tissue was studied from eight juvenile (2-3 mo) and eight adult (5-6 mo) female pigs. Plasma nitric oxide (NO) was measured, and mRNA for endothelium-derived NO synthase (eNOS) and eNOS protein were determined in aortic endothelial cells. Rings of coronary arteries were suspended for measurement of isometric force in organ chambers. Serum 17beta-estradiol levels were comparable in the two groups, whereas the arithmetic mean of progesterone levels was about two-thirds lower in adults compared with juvenile pigs. Plasma NO was significantly higher in juveniles compared with adults, but mRNA and protein for eNOS were comparable. In coronary arteries, an alpha2-adrenergic agonist caused greater endothelium-dependent relaxations in rings from juvenile compared with adult pigs. Relaxations to bradykinin were similar in arteries from both groups, but inhibition of NO reduced relaxations only in arteries from juvenile pigs. Relaxations from NO were greater in arteries from adult compared with juvenile female pigs. In conclusion, coronary arterial endothelial and smooth muscle responses are selectively modulated at puberty in female pigs. At maturity, plasma NO is reduced and sensitivity of the smooth muscle to exogenous NO is increased. Posttranscriptional regulation of eNOS protein may explain differences in NO bioavailability in juvenile pigs.

  14. The Impact of Adolescent Obesity on Adult Height.

    PubMed

    Brener, Avivit; Bello, Rachel; Lebenthal, Yael; Yackobovitch-Gavan, Michal; Phillip, Moshe; Shalitin, Shlomit

    2017-01-01

    Childhood obesity is a major health concern. Excess adiposity during childhood affects growth and puberty. Our aim was to assess whether genetic adult height is compromised in adolescents with obesity. In a retrospective study of 190 obese patients followed at our Pediatric Endocrinology Institute, adult height and delta height (the difference between adult height and mid-parental height) were compared to those of 150 healthy age-matched normal-weight controls. Review of medical files yielded the relevant clinical and anthropometric data of patients, controls, and parents. Of the 190 obese adolescents, 150 were morbidly obese. The median adult height of morbidly obese males was 174.3 cm, of obese males 174 cm, and of normal-weight males 176 cm (p = 0.025). Delta height of morbidly obese males was -0.5 cm, of obese males -0.8 cm, and of normal-weight males, 3 cm (p < 0.0001). The median adult height of morbidly obese females was 161.3 cm, of obese females 162.8 cm, and of normal-weight females 162 cm (p = 0.37). Delta height of morbidly obese females was -1.85 cm, of obese females -0.95 cm, and of normal-weight females 0.7 cm (p = 0.019). Impairment of potential genetic height was not associated with obesity-related comorbidities. Adolescents with obesity showed impairment of potential genetic adult height as compared to that of normal-weight subjects. © 2017 S. Karger AG, Basel.

  15. Comparative proteomic analyses of macular and peripheral retina of cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Okamoto, Haru; Umeda, Shinsuke; Nozawa, Takehiro; Suzuki, Michihiro T; Yoshikawa, Yasuhiro; Matsuura, Etsuko T; Iwata, Takeshi

    2010-01-01

    The central region of the primate retina is called the macula. The fovea is located at the center of the macula, where the photoreceptors are concentrated to create a neural network adapted for high visual acuity. Damage to the fovea, e.g., by macular dystrophies and age-related macular degeneration, can reduce central visual acuity. The molecular mechanisms leading to these diseases are most likely dependent on the proteins in the macula which differ from those in the peripheral retina in expression level. To investigate whether the distribution of proteins in the macula is different from the peripheral retina, proteomic analyses of tissues from these two regions of cynomolgus monkeys were compared. Two-dimensional gel electrophoresis and mass spectrometry identified 26 proteins that were present only in the macular gel spots. The expression levels of five proteins, cone photoreceptor specific arrestin-C, gamma-synuclein, epidermal fatty acid binding protein, tropomyosin 1alpha chain, and heterogeneous nuclear ribonucleoproteins A2/B1, were significantly higher in the macula than in the peripheral retina. Immunostaining of macula sections by antibodies to each identified protein revealed unique localization in the retina, retinal pigment epithelial cells and the choroidal layer. Some of these proteins were located in cells with higher densities in the macula. We suggest that it will be important to study these proteins to determine their contribution to the pathogenesis and progression of macula diseases.

  16. Sex and age differences in hibernation patterns of common hamsters: adult females hibernate for shorter periods than males.

    PubMed

    Siutz, Carina; Franceschini, Claudia; Millesi, Eva

    2016-08-01

    In this study, we investigated the timing and duration of hibernation as well as body temperature patterns in free-ranging common hamsters (Cricetus cricetus) with regard to sex and age differences. Body temperature was recorded using subcutaneously implanted data loggers. The results demonstrate that although immergence and vernal emergence sequences of sex and age groups resembled those of most hibernators, particularly adult females delayed hibernation onset until up to early January. Thus, in contrast to other hibernators, female common hamsters hibernated for shorter periods than males and correspondingly spent less time in torpor. These sex differences were absent in juvenile hamsters. The period between the termination of hibernation and vernal emergence varied among individuals but did not differ between the sex and age groups. This period of preemergence euthermy was related to emergence body mass: individuals that terminated hibernation earlier in spring and had longer euthermic phases prior to emergence started the active season in a better condition. In addition, males with longer periods of preemergence euthermy had larger testes at emergence. In conclusion, females have to rely on sufficient food stores but may adjust the use of torpor in relation to the available external energy reserves, whereas males show a more pronounced energy-saving strategy by hibernating for longer periods. Nonetheless, food caches seem to be important for both males and females as indicated by the euthermic preemergence phase and the fact that some individuals, mainly yearlings, emerged with a higher body mass than shortly before immergence in autumn.

  17. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: II. Dosimetric calculations

    NASA Astrophysics Data System (ADS)

    Kramer, R.; Cassola, V. F.; Khoury, H. J.; Vieira, J. W.; de Melo Lima, V. J.; Robson Brown, K.

    2010-01-01

    Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been developed in the first part of this study using 3D animation software and anatomical atlases to replace the image-based FAX06 and the MAX06 voxel phantoms. 3D modelling methods allow for phantom development independent from medical images of patients, volunteers or cadavers. The second part of this study investigates the dosimetric implications for organ and tissue equivalent doses due to the anatomical differences between the new and the old phantoms. These differences are mainly caused by the supine position of human bodies during scanning in order to acquire digital images for voxel phantom development. Compared to an upright standing person, in image-based voxel phantoms organs are often coronally shifted towards the head and sometimes the sagittal diameter of the trunk is reduced by a gravitational change of the fat distribution. In addition, volumes of adipose and muscle tissue shielding internal organs are sometimes too small, because adaptation of organ volumes to ICRP-based organ masses often occurs at the expense of general soft tissues, such as adipose, muscle or unspecified soft tissue. These effects have dosimetric consequences, especially for partial body exposure, such as in x-ray diagnosis, but also for whole body external exposure and for internal exposure. Using the EGSnrc Monte Carlo code, internal and external exposure to photons and electrons has been simulated with both pairs of phantoms. The results show differences between organ and tissue equivalent doses for the upright standing FASH/MASH and the image-based supine FAX06/MAX06 phantoms of up to 80% for external exposure and up to 100% for internal exposure. Similar differences were found for external exposure between FASH/MASH and REGINA/REX, the reference voxel phantoms of the International Commission on Radiological Protection. Comparison of effective doses for external photon

  18. Sex Differences in Facial Scanning: Similarities and Dissimilarities between Infants and Adults

    ERIC Educational Resources Information Center

    Rennels, Jennifer L.; Cummings, Andrew J.

    2013-01-01

    When face processing studies find sex differences, male infants appear better at face recognition than female infants, whereas female adults appear better at face recognition than male adults. Both female infants and adults, however, discriminate emotional expressions better than males. To investigate if sex and age differences in facial scanning…

  19. Effects of desiccation stress on adult female longevity in Aedes aegypti and Ae. albopictus (Diptera: Culicidae): results of a systematic review and pooled survival analysis.

    PubMed

    Schmidt, Chris A; Comeau, Genevieve; Monaghan, Andrew J; Williamson, Daniel J; Ernst, Kacey C

    2018-04-25

    Transmission dynamics of mosquito-borne viruses such as dengue, Zika and chikungunya are affected by the longevity of the adult female mosquito. Environmental conditions influence the survival of adult female Aedes mosquitoes, the primary vectors of these viruses. While the association of temperature with Aedes mortality has been relatively well-explored, the role of humidity is less established. The current study's goals were to compile knowledge of the influence of humidity on adult survival in the important vector species Aedes aegypti and Ae. albopictus, and to quantify this relationship while accounting for the modifying effect of temperature. We performed a systematic literature review to identify studies reporting experimental results informing the relationships among temperature, humidity and adult survival in Ae. aegypti and Ae. albopictus. Using a novel simulation approach to harmonize disparate survival data, we conducted pooled survival analyses via stratified and mixed effects Cox regression to estimate temperature-dependent associations between humidity and mortality risk for these species across a broad range of temperatures and vapor pressure deficits. After screening 1517 articles, 17 studies (one in semi-field and 16 in laboratory settings) met inclusion criteria and collectively reported results for 192 survival experiments. We review and synthesize relevant findings from these studies. Our stratified model estimated a strong temperature-dependent association of humidity with mortality in both species, though associations were not significant for Ae. albopictus in the mixed effects model. Lowest mortality risks were estimated around 27.5 °C and 21.5 °C for Ae. aegypti and Ae. albopictus, respectively, and mortality increased non-linearly with decreasing humidity. Aedes aegypti had a survival advantage relative to Ae. albopictus in the stratified model under most conditions, but species differences were not significant in the mixed effects model

  20. Prevalence of vaginitis in different age groups among females in Greece.

    PubMed

    Sianou, Argiri; Galyfos, George; Moragianni, Dimitra; Baka, Stavroula

    2017-08-01

    Patients with vaginitis were classified into four groups: Group A (prepubertal under-aged females); Group B (pubertal under-aged females); Group C (reproductive age adult females); Group D (postmenopausal adult females). All vaginal specimens underwent microscopy, amine testing, Gram staining and culturing. Overall, 163 patients were included (33, 14, 81 and 35 patients, respectively). The most common infection was bacterial vaginosis (BV), followed by Ureaplasma infection, aerobic vaginitis (AV) and candidiasis. The most common AV-associated organism was Escherichia coli and the most common BV-associated organism was Gardnerella vaginalis. AV was more frequent in Group A, BV in Group C and Ureaplasma infections in Groups C/D. Decreased lactobacilli concentrations were associated with BV in fertile patients (Groups B-C). Although presentation of vaginitis is similar among females of different age in Greece, type and prevalence of pathogens differ. Normal vaginal flora changes are associated with higher risk of vaginitis in specific age groups. Impact Statement The worldwide incidence of reproductive tract infections has been increasing, with specific pathogens being associated with significant risk of morbidity and complications. However, literature data on the distribution of such infections in different age groups is limited. Therefore, the aim of this study was to provide data on the prevalence and causes of vaginitis in adult and non-adult females of all ages. This study has shown that although presentation of vaginitis is similar among females of different age groups and menstrual status in Greece, type and prevalence of responsible pathogens are different among groups. Changes in normal vaginal flora seem to be associated with higher risk of vaginitis in specific age-groups as well. These findings could contribute in adjusting diagnostic and therapeutic strategies for each age group according to the prevailing pathogens. Further research on antibiotic

  1. Courtship song preferences in female zebra finches are shaped by developmental auditory experience.

    PubMed

    Chen, Yining; Clark, Oliver; Woolley, Sarah C

    2017-05-31

    The performance of courtship signals provides information about the behavioural state and quality of the signaller, and females can use such information for social decision-making (e.g. mate choice). However, relatively little is known about the degree to which the perception of and preference for differences in motor performance are shaped by developmental experiences. Furthermore, the neural substrates that development could act upon to influence the processing of performance features remains largely unknown. In songbirds, females use song to identify males and select mates. Moreover, female songbirds are often sensitive to variation in male song performance. Consequently, we investigated how developmental exposure to adult male song affected behavioural and neural responses to song in a small, gregarious songbird, the zebra finch. Zebra finch males modulate their song performance when courting females, and previous work has shown that females prefer the high-performance, female-directed courtship song. However, unlike females allowed to hear and interact with an adult male during development, females reared without developmental song exposure did not demonstrate behavioural preferences for high-performance courtship songs. Additionally, auditory responses to courtship and non-courtship song were altered in adult females raised without developmental song exposure. These data highlight the critical role of developmental auditory experience in shaping the perception and processing of song performance. © 2017 The Author(s).

  2. Female sexual dysfunction and adolescents.

    PubMed

    Greydanus, Donald E; Matytsina, Lyubov

    2010-10-01

    To review recent publications in the area of sexual dysfunction in females including the adolescent age group. Though as many as 40% of adult females have a sexual dysfunction, the incidence among adolescent females is unknown. Though over half of adolescents are sexually active, sexual dysfunction is not a term universally accepted among the general public as well as researchers. Research on sexual dysfunction in females typically starts with age 18 years or over. Causes of sexual dysfunction include medical disorders, gynecological problems, which started from the adolescent age, psychiatric disorders, and complications of medications such as selective serotonin reuptake inhibitors (SSRIs), antipsychotics, and others. Management includes identification of the specific sexual dysfunction and treatment of the underlying condition, including surgical treatment in such cases as absent vagina or obstetrics fistula. Psychological therapy is helpful when psychological factors are contributory to the dysfunction. Pharmacologic principles of management cases can, for example, include treatment of gynecological problems such as pelvic inflammatory disease (PID) or endometriosis as a cause of sexual dysfunction or include removal of the offending drug, use of glutamatergic strategies or trazodone in SSRI-association dysfunction, and addition of bupropion or other medications in select cases. No medication is FDA-approved for sexual dysfunction in females. Sexual dysfunction in females includes lack of sexual desire, sexual pain disorders (as dyspareunia), anorgasmia, and sexual arousal dysfunction. Acceptance of the high incidence of sexual dysfunction in all female populations is necessary to appreciate this phenomenon in the adolescent cohort, because some gynecological disease can arise from the adolescent age and can cause sexual dysfunction. Some sexual dysfunctions require immediate treatment, including surgical in the case of congenital anomaly, ovarian cyst, or

  3. Adult Education for Women.

    ERIC Educational Resources Information Center

    Nagappa, T. R.

    1980-01-01

    Apathy, indifference, and neglect has characterized adult education for women in India. The National Adult Education Programme must focus attention and funding on women if the extremely low percentage of female literacy is to be improved. (SK)

  4. Racial/Ethnic Differences in Patterns of Sexual Risk Behavior and Rates of Sexually Transmitted Infections Among Female Young Adults

    PubMed Central

    Cook, Emily C.; Niccolai, Linda M.; Connell, Christian M.

    2013-01-01

    Objectives. We examined patterns of sexual behavior and risk for sexually transmitted infections (STIs) in young adulthood for Black, Hispanic, and White females. Methods. We used a nationally representative sample of 7015 female young adults from wave III of the National Longitudinal Study of Adolescent Health. Sexual risk items assessed behaviors occurring in the previous 6 years and past year to determine classes of sexual risk and links to STIs in young adulthood. Results. Latent class analysis revealed 3 sexual risk classes for Black and Hispanic youths and 4 sexual risk classes for White youths. The moderate and high risk classes had the highest probabilities of risky sexual partners, inconsistent condom use, and early age of sexual initiation, which significantly increased odds for STIs compared with recent abstainers. Conclusions. We found different classes of sexual behavior by race/ethnicity, with Black and Hispanic young women most at risk for STIs in young adulthood. Preventive efforts should target younger adolescents and focus on sexual partner behavior. PMID:23488501

  5. Infants Prefer Female Body Phenotypes; Infant Girls Prefer They Have an Hourglass Shape

    PubMed Central

    Alexander, Gerianne M.; Hawkins, Laura B.; Wilcox, Teresa; Hirshkowitz, Amy

    2016-01-01

    Adolescents and adults show preferences for male and female body shapes consistent with evolutionary theories of reproductive fitness and mate selection. However, when these preferences for females with narrow waists (i.e., 0.7 waist-to-hip ratio) and men with broad shoulders (i.e., mesomorphic body shape) emerge during the lifespan is largely unknown. To address this knowledge gap, eye-movements were tracked in 146 infants (3–18 months of age) during computer presentation of three-dimensional human figures varying in body features thought relevant for reproductive success (e.g., secondary sex characteristics, waist-to-hip ratio). When presented with pairs of figures differing in apparent sex, male and female infants looked significantly longer at the female figure compared to the male figure, a new finding that extends previous research showing preferences for female faces in infancy. When presented with same-sex figures differing in characteristics associated with mate value, male and female infants looked longer at a low mate value male (i.e., an endomorphic body type) compared to a high mate value male (i.e., a mesomorphic body type), a finding that replicates the results of previous research. In addition, the novel use of high and low mate value female figures showed a sex difference in visual attention, such that female infants looked longer at the high mate value female figure compared to the low mate female figure whereas male infants showed the opposite pattern of results. In sum, these findings suggest that infants generally do not possess preferences for adult-defined attractive male body shapes. However, infant girls’ greater attention to a female figure with an adult-preferred waist-to-hip ratio raises the possibility that evolved preferences for 0.7 waist-to-hip ratio influence girls’ later preference for toys representing females with an hourglass shape, perhaps supporting elaboration of adult social behaviors that enhance reproductive success

  6. A randomized comparative trial of a combined oral contraceptive and azelaic acid to assess their effect on sleep quality in adult female acne patients.

    PubMed

    Albuquerque, Rachel Gimenes; da Rocha, Marco Alexandre Dias; Hirotsu, Camila; Hachul, Helena; Bagatin, Edileia; Tufik, Sergio; Andersen, Monica Levy

    2015-12-01

    Several studies have reported an increase in the prevalence of adult female acne. This subtype of acne presents particular characteristics, and can be triggered by several factors such as smoking, stress, the use of oily cosmetics and even by poor sleep. Sleep quality is related to well-being and the maintenance of body homeostasis. In addition, several skin diseases present a bidirectional relationship with sleep, demonstrating an important connection between skin and the central nervous system. With this in mind, we aimed to compare the effect of two types of treatment for adult female acne (azelaic acid or a combined oral contraceptive) on sleep quality and on concentrations of stress hormones. Also, we proposed to assess the correlation of sleep and hormonal parameters with acne severity. In order to do this, 32 women underwent a clinical evaluation, completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire and had their blood collected for hormone assays. These procedures were performed at baseline and after 6 months of treatment. At baseline there were no differences between the groups in terms of body mass index, age, acne severity and hormone concentrations. Results showed that both treatments demonstrated effectiveness but that women treated with azelaic acid presented a better sleep quality after the treatment compared to baseline and to the group treated with the combined oral contraceptive. The combined oral contraceptive group presented an increase in cortisol and a decrease in free testosterone concentration in relation to baseline. These data suggest that both azelaic acid and combined oral contraceptive are effective in the treatment of adult female acne but, azelaic acid seems to be a more suitable option for those women who may benefit from a better subjective sleep quality.

  7. Feeding frequency, but not dietary water content, affects voluntary physical activity in young lean adult female cats.

    PubMed

    de Godoy, M R C; Ochi, K; de Oliveira Mateus, L F; de Justino, A C C; Swanson, K S

    2015-05-01

    The objective of this study was to investigate whether increased dietary water content and feeding frequency increased voluntary physical activity of young, lean adult female cats. A replicated 4 × 4 Latin square design with a 2 × 2 factorial treatment arrangement (feeding frequency and water content) was used. The 4 treatments consisted of 1 meal daily dry pet food without added water (1D; 12% moisture as is), 1 meal daily dry pet food with added water (1W; 70% total water content), 4 meals daily dry pet food without added water (4D; 12% moisture as is), and 4 meals daily dry pet food with added water (4W; 70% total water content). Eight healthy adult, lean, intact, young, female domestic shorthair cats were used in this experiment. Voluntary physical activity was evaluated using Actical activity monitors placed on collars and worn around the cats' necks for the last 7 d of each experimental period of 14 d. Food anticipatory activity (FAA) was calculated based on 2 h prior to feeding periods and expressed as a percentage of total daily voluntary physical activity. Increased feeding frequency (4 vs. 1 meal daily) resulted in greater average daily activity (P = 0.0147), activity during the light period (P = 0.0023), and light:dark activity ratio (P = 0.0002). In contrast, physical activity during the dark period was not altered by feeding frequency (P > 0.05). Cats fed 4 meals daily had increased afternoon FAA (P= 0.0029) compared with cats fed once daily. Dietary water content did not affect any measure of voluntary physical activity. Increased feeding frequency is an effective strategy to increase the voluntary physical activity of cats. Thus, it may assist in the prevention and management of obesity.

  8. Adult Women in Community Colleges. ERIC Digest.

    ERIC Educational Resources Information Center

    White, Janene

    This digest reviews some of the recent literature about adult female students at community colleges. Their motivations, unique needs, and barriers to entry are discussed, as well as ways institutions can enhance the educational experience for adult women. Female students have outnumbered male students in higher education for nearly 30 years. In…

  9. Comparison of trunk acceleration ratios during stair negotiation in old-old females.

    PubMed

    Shin, Sun-Shil; Yoo, Won-Gyu

    2016-06-01

    [Purpose] This study compared trunk acceleration ratios in old-old adult females during stair negotiation. [Subjects and Methods] Twelve old-old adult females who could walk independently volunteered for this study. This study measured gait time and trunk acceleration ratios using an accelerometer during ascending and descending stairs [Results] The trunk acceleration ratio when descending stairs was significantly higher than that when ascending stairs. [Conclusion] These findings suggest that old-old females have greater deterioration of upper trunk control function for descending than for ascending stairs, regardless of task time. In addition, the trunk acceleration ratio during stair negotiation is a useful clinical marker to predict function and balance control ability in old-old females.

  10. Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

    PubMed

    Chachlaki, Konstantina; Malone, Samuel A; Qualls-Creekmore, Emily; Hrabovszky, Erik; Münzberg, Heike; Giacobini, Paolo; Ango, Fabrice; Prevot, Vincent

    2017-10-15

    Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFP Vglut2 , EYFP Vgat , and GFP Gad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes. © 2017 Wiley Periodicals, Inc.

  11. Combined androgen excess and Western-style diet accelerates adipose tissue dysfunction in young adult, female nonhuman primates.

    PubMed

    Varlamov, Oleg; Bishop, Cecily V; Handu, Mithila; Takahashi, Diana; Srinivasan, Sathya; White, Ashley; Roberts, Charles T

    2017-09-01

    What are the separate and combined effects of mild hyperandrogenemia and consumption of a high-fat Western-style diet (WSD) on white adipose tissue (WAT) morphology and function in young adult female nonhuman primates? Combined exposure to mild hyperandrogenemia and WSD induces visceral omental (OM-WAT) but not subcutaneous (SC-WAT) adipocyte hypertrophy that is associated with increased uptake and reduced mobilization of free fatty acids. Mild hyperandrogenemia in females, principally in the context of polycystic ovary syndrome, is often associated with adipocyte hypertrophy, but the mechanisms of associated WAT dysfunction and depot specificity remain poorly understood. Female rhesus macaques were randomly assigned at 2.5 years of age (near menarche) to receive either cholesterol (C; n = 20) or testosterone (T; n = 20)-containing silastic implants to elevate T levels 5-fold above baseline. Half of each of these groups was then fed either a low-fat monkey chow diet or WSD, resulting in four treatment groups (C, control diet; T alone; WSD alone; T + WSD; n = 10/group) that were maintained until the current analyses were performed at 5.5 years of age (3 years of treatment, young adults). OM and SC-WAT biopsies were collected and analyzed longitudinally for in vivo changes in adipocyte area and blood vessel density, and ex vivo basal and insulin-stimulated fatty acid uptake and basal and isoproterenol-stimulated lipolysis. In years 2 and 3 of treatment, the T + WSD group exhibited a significantly greater increase in OM adipocyte size compared to all other groups (P < 0.05), while the size of SC adipocytes measured at the end of the study was not significantly different between groups. In year 3, both WAT depots from the WSD and T + WSD groups displayed a significant reduction in local capillary length and vessel junction density (P < 0.05). In year 3, insulin-stimulated fatty acid uptake in OM-WAT was increased in the T + WSD group compared to year 2 (P < 0.05). In

  12. Effect of High Fructose Corn Syrup (HFCS) Intake on the Female Reproductive Organs and Lipid Accumulation in Adult Rats

    PubMed Central

    Ko, Eun-Ah; Kim, Hye-Ri; Kim, Yong-Bin; Kim, Hee-Su; Lee, Sung-Ho

    2017-01-01

    ABSTRACT High-fructose corn syrup (HFCS) is widely used as sweetener, and its overconsumption is become a major health problem. In the present study, we used adult female rats and applied a 28 days HFCS feeding model to monitor the estrous cycle and changes in tissue weights and histology. Adult female rats were divided into three groups. Animals were fed with ad libitum normal chow and (1) 24 hours tap water (Control group), (2) 12 hours HFCS access during dark period and 12 hours tap water (12H group), and (3) 24 hours HFCS only access (24H group). Total exposure period was 28 days. There is no significant change in body weight between control and HFCS-fed animals. Both absolute and relative weights of ovary in 24H animals were significantly heavier than those in control or 12H animals. The absolute and relative weights of the kidney and liver in 24H groups were significantly heavier than those in control or 12H animals. The estrous cycles of the 24H animals were significantly longer. Histological analyses revealed that 24H ovaries were relatively bigger and possessed more corpus lutea than control ovaries. Uterine sections of 12H and 24H animals showed a well-developed stratum vasculare between inner and outer myometrial layers. The number of endometrial glands were decreased in 12H uteri, and recovered in 24H uteri compared to control. Numbers of convoluted tubule in distal region increased in 12H and 24H kidney samples. Liver specimens of 12H and 24H showed the increased number of fat containing vacuoles. In conclusion, our study demonstrated that HFCS treatment for 28 days could induce (1) changes in length of estrous cycle with extended estrous and diestrous stages, (2) altered ovarian and uterine histology, and (3) liver and renal lipid accumulation. These findings reveal the adverse effects of HFCS drinking on the reproductive function and lipid metabolism of female rats. PMID:28785736

  13. Effect of High Fructose Corn Syrup (HFCS) Intake on the Female Reproductive Organs and Lipid Accumulation in Adult Rats.

    PubMed

    Ko, Eun-Ah; Kim, Hye-Ri; Kim, Yong-Bin; Kim, Hee-Su; Lee, Sung-Ho

    2017-06-01

    High-fructose corn syrup (HFCS) is widely used as sweetener, and its overconsumption is become a major health problem. In the present study, we used adult female rats and applied a 28 days HFCS feeding model to monitor the estrous cycle and changes in tissue weights and histology. Adult female rats were divided into three groups. Animals were fed with ad libitum normal chow and (1) 24 hours tap water (Control group), (2) 12 hours HFCS access during dark period and 12 hours tap water (12H group), and (3) 24 hours HFCS only access (24H group). Total exposure period was 28 days. There is no significant change in body weight between control and HFCS-fed animals. Both absolute and relative weights of ovary in 24H animals were significantly heavier than those in control or 12H animals. The absolute and relative weights of the kidney and liver in 24H groups were significantly heavier than those in control or 12H animals. The estrous cycles of the 24H animals were significantly longer. Histological analyses revealed that 24H ovaries were relatively bigger and possessed more corpus lutea than control ovaries. Uterine sections of 12H and 24H animals showed a well-developed stratum vasculare between inner and outer myometrial layers. The number of endometrial glands were decreased in 12H uteri, and recovered in 24H uteri compared to control. Numbers of convoluted tubule in distal region increased in 12H and 24H kidney samples. Liver specimens of 12H and 24H showed the increased number of fat containing vacuoles. In conclusion, our study demonstrated that HFCS treatment for 28 days could induce (1) changes in length of estrous cycle with extended estrous and diestrous stages, (2) altered ovarian and uterine histology, and (3) liver and renal lipid accumulation. These findings reveal the adverse effects of HFCS drinking on the reproductive function and lipid metabolism of female rats.

  14. Development of an Inhalational Bacillus anthracis Exposure Therapeutic Model in Cynomolgus Macaques

    PubMed Central

    Comer, Jason E.; Stark, Gregory V.; Ray, Bryan D.; Tordoff, Kevin P.; Knostman, Katherine A. B.; Meister, Gabriel T.

    2012-01-01

    Appropriate animal models are required to test medical countermeasures to bioterrorist threats. To that end, we characterized a nonhuman primate (NHP) inhalational anthrax therapeutic model for use in testing anthrax therapeutic medical countermeasures according to the U.S. Food and Drug Administration Animal Rule. A clinical profile was recorded for each NHP exposed to a lethal dose of Bacillus anthracis Ames spores. Specific diagnostic parameters were detected relatively early in disease progression, i.e., by blood culture (∼37 h postchallenge) and the presence of circulating protective antigen (PA) detected by electrochemiluminescence (ECL) ∼38 h postchallenge, whereas nonspecific clinical signs of disease, i.e., changes in body temperature, hematologic parameters (ca. 52 to 66 h), and clinical observations, were delayed. To determine whether the presentation of antigenemia (PA in the blood) was an appropriate trigger for therapeutic intervention, a monoclonal antibody specific for PA was administered to 12 additional animals after the circulating levels of PA were detected by ECL. Seventy-five percent of the monoclonal antibody-treated animals survived compared to 17% of the untreated controls, suggesting that intervention at the onset of antigenemia is an appropriate treatment trigger for this model. Moreover, the onset of antigenemia correlated with bacteremia, and NHPs were treated in a therapeutic manner. Interestingly, brain lesions were observed by histopathology in the treated nonsurviving animals, whereas this observation was absent from 90% of the nonsurviving untreated animals. Our results support the use of the cynomolgus macaque as an appropriate therapeutic animal model for assessing the efficacy of medical countermeasures developed against anthrax when administered after a confirmation of infection. PMID:22956657

  15. A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques.

    PubMed

    Peluffo, M C; Stanley, J; Braeuer, N; Rotgeri, A; Fritzemeier, K-H; Fuhrmann, U; Buchmann, B; Adevai, T; Murphy, M J; Zelinski, M B; Lindenthal, B; Hennebold, J D; Stouffer, R L

    2014-07-01

    Can administration of a prostaglandin (PG) E2 receptor 2 (PTGER2) antagonist prevent pregnancy in adult female monkeys by blocking periovulatory events in the follicle without altering menstrual cyclicity or general health? This is the first study to demonstrate that a PTGER2 antagonist can serve as an effective non-hormonal contraceptive in primates. The requirement for PGE2 in ovulation and the release of an oocyte surrounded by expanded cumulus cells (cumulus-oocyte expansion; C-OE) was established through the generation of PTGS2 and PTGER2 null-mutant mice. A critical role for PGE2 in primate ovulation is supported by evidence that intrafollicular injection of indomethacin in rhesus monkeys suppressed follicle rupture, whereas co-injection of PGE2 with indomethacin resulted in ovulation. First, controlled ovulation protocols were performed in adult, female rhesus monkeys to analyze the mRNA levels for genes encoding PGE2 synthesis and signaling components in the naturally selected pre-ovulatory follicle at different times after the ovulatory hCG stimulus (0, 12, 24, 36 h pre-ovulation; 36 h post-ovulation, n = 3-4/time point). Second, controlled ovarian stimulation cycles were utilized to obtain multiple cumulus-oocyte complexes (COCs) from rhesus monkeys to evaluate the role of PGE2 in C-OE in vitro (n = 3-4 animals/treatment; ≥3 COCs/animal/treatment). Third, adult cycling female cynomolgus macaques were randomly assigned (n = 10/group) to vehicle (control) or PTGER2 antagonist (BAY06) groups to perform a contraceptive trial. After the first treatment cycle, a male of proven fertility was introduced into each group and they remained housed together for the duration of the 5-month contraceptive trial that was followed by a post-treatment reversibility trial. Quantitative real-time PCR, COC culture and expansion, immunofluorescence/confocal microscopy, enzyme immunoassay, contraceptive trial, ultrasonography, complete blood counts, serum biochemistry tests

  16. Effects of Anethum graveolens L. (dill) on Oocyte and Fertility of Adult Female Rats

    PubMed Central

    Monsefi, Malihezaman; Ghasemi, Aazam; Alaee, Sanaz; Aliabadi, Elham

    2015-01-01

    Background Our previous studies revealed Anethum graveolens L. caused some changes in female reproductive system that induced infertility. Therefore, in this study, oocyte changes as one of probable reasons of infertility were investigated. Methods In this study, 59 adult female rats were divided into 3 groups of control, low dose (0.5 g/kg) and high dose (5 g/kg) of dill seed aqueous extract (LDE and HDE) treated groups that were gavaged with 1 ml of each dose for 10 days (2 estrous cycles). Vaginal smears were prepared daily. Oocytes of superovulated animals were extracted and their morphometrical changes were measured (n = 5). Oocyte cell membrane glycoconjugates were stained with UEA, PNA, and DBA-FITC lectins (n = 5). Ultrastructural studies of oocytes were performed using TEM (n = 5). The number, weight, and crown-rump length of newborns were examined in three groups after mating with untreated males (n = 5). Data were analyzed using SPSS software. Results Results demonstrated that the duration of the estrous cycle, the diestrus phase and progesterone concentration in the experimental groups increased significantly compared to the control group (p < 0.05). Granulosa cells of corpus luteum in HDE-treated group were larger and clearer. The intensity reactions of galactose/Nacetylgalactoseamine terminal sugar of oocyte decreased insignificantly in experimental groups compared to the control group p > 0.05. Duration of mating to pregnancy increased and the weight and crown-rump length of newborns decreased in experimental groups significantly (p < 0.05). Conclusion Dill seed aqueous extract can induce infertility without any effect on oocyte structure. PMID:25717430

  17. Female-biased sex ratio, polygyny, and persistence in the endangered Southwestern Willow Flycatcher (Empidonax traillii extimus)

    USGS Publications Warehouse

    Kus, Barbara E.; Howell, Scarlett; Wood, Dustin A.

    2017-01-01

    Demographic changes in populations, such as skewed sex ratios, are of concern to conservationists, especially in small populations in which stochastic and other events can produce declines leading to extirpation. We documented a decline in one of the few remaining populations of Southwestern Willow Flycatcher (Empidonax traillii extimus) in southern California, USA, which dropped from 40 to 5 adults between 2000 and 2015. Declines were unequal between sexes (94% for males, 82% for females). Adult sex ratios were female-biased in 10 of 16 yr. The proportion of paired males that were polygynous ranged from 0% to 100%, depending on the ratio of females to males in the adult population. Some males paired with up to 5 females simultaneously. We investigated the role of nestling sex ratio in the female-biased adult sex ratio by using genetic techniques to determine sex from blood samples collected from 162 nestlings in 72 nests from 2002 to 2009. Both population-level and within-brood nestling sex ratios were female-biased, and were not influenced by nest order (first or subsequent), parental mating type (monogamous or polygynous), or year. Disproportionately more females than males were recruited into the breeding population, mirroring nestling and fledgling sex ratios. It thus appears that a skewed nestling sex ratio has contributed to a female-biased adult population, which in turn has influenced mating behavior. We propose that the capacity for polygyny, which generally occurs at low levels in Southwestern Willow Flycatchers, has allowed this population to persist through a decline that might otherwise have resulted in extinction.

  18. Physiology and Endocrinology of the Ovarian Cycle in Macaques

    PubMed Central

    Weinbauer, Gerhard F.; Niehoff, Marc; Niehaus, Michael; Srivastav, Shiela; Fuchs, Antje; Van Esch, Eric; Cline, J. Mark

    2009-01-01

    Macaques provide excellent models for preclinical testing and safety assessment of female reproductive toxicants. Currently, cynomolgus monkeys are the predominant species for (reproductive) toxicity testing. Marmosets and rhesus monkeys are being used occasionally. The authors provide a brief review on physiology and endocrinology of the cynomolgus monkey ovarian cycle, practical guidance on assessment and monitoring of ovarian cyclicity, and new data on effects of social housing on ovarian cyclicity in toxicological studies. In macaques, cycle monitoring is achieved using daily vaginal smears for menstruation combined with cycle-timed frequent sampling for steroid and peptide hormone analysis. Owing to requirements of frequent and timed blood sampling, it is not recommended to incorporate these special evaluations into a general toxicity study design. Marmosets lack external signs of ovarian cyclicity, and cycle monitoring is done by regular determinations of progesterone. Cynomolgus and marmoset monkeys do not exhibit seasonal variations in ovarian activity, whereas such annual rhythm is pronounced in rhesus monkeys. Studies on pair- and group-housed cynomolgus monkeys revealed transient alterations in the duration and endocrinology of the ovarian cycle followed by return to normal cyclicity after approximately six months. This effect is avoided if the animals had contact with each other prior to mingling. These experiments also demonstrated that synchronization of ovarian cycles did not occur. PMID:20852722

  19. Effects of sex pheromones and sexual maturation on locomotor activity in female sea lamprey (Petromyzon marinus)

    USGS Publications Warehouse

    Walaszczyk, Erin J.; Johnson, Nicholas S.; Steibel, Juan Pedro; Li, Weiming

    2013-01-01

    Synchronization of male and female locomotor rhythmicity can play a vital role in ensuring reproductive success. Several physiological and environmental factors alter these locomotor rhythms. As sea lamprey, Petromyzon marinus, progress through their life cycle, their locomotor activity rhythm changes multiple times. The goal of this study was to elucidate the activity patterns of adult female sea lamprey during the sexual maturation process and discern the interactions of these patterns with exposure to male pheromones. During these stages, preovulated and ovulated adult females are exposed to sex pheromone compounds, which are released by spermiated males and attract ovulated females to the nest for spawning. The locomotor behavior of adult females was monitored in a natural stream with a passive integrated tag responder system as they matured, and they were exposed to a sex pheromone treatment (spermiated male washings) or a control (prespermiated male washings). Results showed that, dependent on the hour of day, male sex pheromone compounds reduce total activity (p < 0.05) and cause increases in activity during several daytime hours in preovulated and ovulated females. These results are one of the first examples of how sex pheromones modulate a locomotor rhythm in a vertebrate, and they suggest that the interaction between maturity stage and sex pheromone exposure contributes to the differential locomotor rhythms found in adult female sea lamprey. This phenomenon may contribute to the reproductive synchrony of mature adults, thus increasing reproductive success in this species.

  20. Ectoparasites and fitness of female Columbian ground squirrels

    PubMed Central

    Raveh, Shirley; Neuhaus, Peter; Dobson, F. Stephen

    2015-01-01

    Parasites play an important role in the evolution of host traits via natural selection, coevolution and sexually selected ornaments used in mate choice. These evolutionary scenarios assume fitness costs for hosts. To test this assumption, we conducted an ectoparasite removal experiment in free-living Columbian ground squirrels (Urocittelus columbianus) in four populations over three years. Adult females were randomly chosen to be either experimentally treated with anti-parasite treatments (spot-on solution and flea powder, N = 61) or a sham treatment (control, N = 44). We expected that experimental females would show better body condition, increased reproductive success and enhanced survival. Contrary to our expectations, body mass was not significantly different between treatments at mating, birth of litter or weaning of young. Further, neither number nor size of young at weaning differed significantly between the two treatments. Survival to the next spring for adult females and juveniles was not significantly different between experimental and control treatments. Finally, annual fitness was not affected by the treatments. We concluded that females and their offspring were able compensate for the presence of ectoparasites, suggesting little or no fitness costs of parasites for females in the different colonies and during the years of our experiments. PMID:25870399

  1. Are treatment results for eating disorders affected by ADHD symptoms? A one-year follow-up of adult females.

    PubMed

    Svedlund, Nils Erik; Norring, Claes; Ginsberg, Ylva; von Hausswolff-Juhlin, Yvonne

    2018-05-02

    To explore the influence of self-reported Attention Deficit Hyperactivity Disorder (ADHD) symptoms on recovery rate at 1-year follow-up in an unselected group of patients in a specialized eating disorder (ED) clinic. Four hundred forty-three adult females with an ED were assessed with the ADHD Self-Report Scale for Adults (ASRS-screener), and for demographic variables and ED symptoms. Recovery was registered at 1-year follow-up. A high degree of ADHD symptoms at baseline was predictive for nonrecovery of ED at 1-year follow-up in patients with loss of control over eating, bingeing, or purging. The presence of inattentive ADHD symptoms was stronger associated with nonrecovery than hyperactive/impulsive symptoms. A high degree of ADHD symptoms may have a negative impact on recovery in ED. Screening/diagnostic evaluation of ADHD in all loss of control over eating/bingeing/purging ED patients and studies of the effect of implementing ADHD-treatment strategies in this patient group are recommended. Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.

  2. Adolescent Male-to-Female Transgender Voice and Communication Therapy

    ERIC Educational Resources Information Center

    Hancock, Adrienne; Helenius, Lauren

    2012-01-01

    Current research to describe and evaluate effectiveness of voice and communication therapy for male-to-female transgender people is limited to adults. This paper provides rationale, procedures, and outcomes from voice and communication therapy for a male-to-female transgender adolescent 15 years of age. Treatment addressed vocal hygiene, breath…

  3. Azelaic acid 20 % cream: effects on quality of life and disease severity in adult female acne patients.

    PubMed

    Kainz, Julius Thomas; Berghammer, Gabriele; Auer-Grumbach, Piet; Lackner, Verena; Perl-Convalexius, Sylvia; Popa, Rodica; Wolfesberger, Barbara

    2016-12-01

    Data on the efficacy of acne treatments and their impact on quality of life (QoL) in adult patients is sketchy. Assessment of the efficacy of azelaic acid 20 % cream (Skinoren ® ) on acne severity and disease-related QoL. Noninterventional study in adult female patients with mild to moderate acne. Efficacy variables included DLQI and acne severity on the face, chest, and back using the Investigator's Global Assessment (IGA) scale (grade 1 = nearly clear skin; 2 = mild acne; 3 = moderate acne). Visits were scheduled at baseline, at 4-8 weeks, and at twelve weeks. Of the 251 women enrolled, 59 % had grade 1 acne at baseline; 31 %, grade 2; and 10 %, grade 3; the most commonly affected area of the body was the face (IGA grades 2 or 3: 79 %). After twelve weeks, there was significant improvement of acne on the face (IGA grades 0 or 1: 82 %), chest, and back. Median DLQI decreased from nine at baseline to five after twelve weeks. Ninety percent of physicians and patients rated the tolerability of the treatment as very good or good. Treatment with azelaic acid 20 % cream significantly improves acne severity and disease-related QoL in adult women. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  4. [Stimulation of D1-receptors improves passive avoidance learning of female rats during ovary cycle].

    PubMed

    Fedotova, Iu O; Sapronov, N S

    2012-01-01

    The involvement of D1-receptors in learning/memory processes during ovary cycle was assessed in the adult female rats. SKF-38393 (0,1 mg/kg, i.p.), D1-receptor agonist and SCH-23390 (0,1 mg/kg, i.p.), D1-receptor antagonist were injected chronically to adult female rats. Learning of these animals was assessed in different models: passive avoidance performance and Morris water maze. Chronic SKF-3839 administration to females resulted in the appearance of the passive avoidance performance in proestrous and estrous, as distinct from the control animals, but failed to change the dynamics of spatial learning in Morris water maze. Chronic SCH-23390 administration similarly impaired non-spatial and spatial learning in females during all phases of ovary cycle. The results of the study suggest modulating role of D1-receptors in learning/memory processes during ovary cycle in the adult female rats.

  5. Assessment of body perception among Swedish adolescents and young adults.

    PubMed

    Bergström, E; Stenlund, H; Svedjehäll, B

    2000-01-01

    To assess body perception in adolescents and young adults without anorexia nervosa. Using a visual size estimation technique, perceived body size was estimated in four groups of Swedish adolescents and young adults without anorexia nervosa (86 males and 95 females). Perceived body size was estimated at nine different body sites comparing these estimations to real body size. The results show that 95% of males and 96% of females overestimated their body size (mean overestimation: males +22%, females +33%). The overestimations were greatest in females. The greatest overestimations were made of the waist (males +31%, females +46%), buttocks (males +22%, females +42%), and thighs (males +27%, females +41%). The results indicate that overestimation of body size may be a general phenomenon in adolescents and young adults in a country such as Sweden, implying a similar, but less pronounced distortion of body image as in individuals with anorexia nervosa.

  6. Neurokinin B is critical for normal timing of sexual maturation but dispensable for adult reproductive function in female mice.

    PubMed

    True, Cadence; Nasrin Alam, Sayeda; Cox, Kimberly; Chan, Yee-Ming; Seminara, Stephanie B

    2015-04-01

    Humans carrying mutations in neurokinin B (NKB) or the NKB receptor fail to undergo puberty due to decreased secretion of GnRH. Despite this pubertal delay, many of these patients go on to achieve activation of their hypothalamic-pituitary-gonadal axis in adulthood, a phenomenon termed reversal, indicating that NKB signaling may play a more critical role for the timing of pubertal development than adult reproductive function. NKB receptor-deficient mice are hypogonadotropic but have no defects in the timing of sexual maturation. The current study has performed the first phenotypic evaluation of mice bearing mutations in Tac2, the gene encoding the NKB ligand, to determine whether they have impaired sexual development similar to their human counterparts. Male Tac2-/- mice showed no difference in the timing of sexual maturation or fertility compared with wild-type littermates and were fertile. In contrast, Tac2-/- females had profound delays in sexual maturation, with time to vaginal opening and first estrus occurring significantly later than controls, and initial abnormalities in estrous cycles. However, cycling recovered in adulthood and Tac2-/- females were fertile, although they produced fewer pups per litter. Thus, female Tac2-/- mice parallel humans harboring NKB pathway mutations, with delayed sexual maturation and activation of the reproductive cascade later in life. Moreover, direct comparison of NKB ligand and receptor-deficient females confirmed that only NKB ligand-deficient animals have delayed sexual maturation, suggesting that in the absence of the NKB receptor, NKB may regulate the timing of sexual maturation through other tachykinin receptors.

  7. Passive Response to Stress in Adolescent Female and Adult Male Mice after Intermittent Nicotine Exposure in Adolescence

    PubMed Central

    Thanos, Panayotis; Delis, Foteini; Rosko, Lauren; Volkow, Nora D

    2013-01-01

    Smoking is frequently co-morbid with depression. Although it is recognized that depression increases the risk for smoking, it is unclear if early smoking exposure may increase the risk for depression. To test this possibility we assessed the effects of adolescent nicotine exposure on the Forced Swim Test (FST), which is used as a measure of passive coping, and depressive-like behavior in rodents, and on the open field test (OFT), which is used as a measure of locomotion and exploratory behavior. Male and female mice received daily saline or nicotine (0.3 or 0.6 mg/kg) injections from postnatal day (PD) 30 to PD 44. FST and OFT were performed either 1 or 30 days after the last injection (PD 45 and PD 74, respectively). In females, treatment with 0.3 mg/kg nicotine lead to increased FST immobility (64%) and decreased OFT locomotor activity (12%) one day following the last nicotine injection (PD 45); while no effects were observed in adulthood (PD 74). In contrast, on PD45, nicotine treatment did not change the male FST immobility but lead to lower OFT locomotor activity (0.6 mg/kg, 10%). In adulthood (PD 74), both nicotine doses lead to higher FST immobility (87%) in males while 0.6 mg/kg nicotine to lower OFT locomotor activity (13%). The results (i) identify females as more vulnerable to the immediate withdrawal that follows nicotine discontinuation in adolescence and (ii) suggest that adolescent nicotine exposure may enhance the risk for passive response towards unavoidable stress in adult males. PMID:24619539

  8. Intake of Erythrocytes Required for Reproductive Development of Female Schistosoma japonicum.

    PubMed

    Wang, Jipeng; Wang, Shuqi; Liu, Xiufeng; Xu, Bin; Chai, Riyi; Zhou, Pan; Ju, Chuan; Sun, Jun; Brindley, Paul J; Hu, Wei

    2015-01-01

    The reproductive development and maturation of female schistosomes are crucial since their released eggs are responsible for the host immunopathology and transmission of schistosomiasis. However, little is known about the nutrients required by female Schistosoma japonicum during its sexual maturation. We evaluated the promoting effect of several nutrients (calf serum, red blood cells (RBCs), ATP and hypoxanthine) on the reproductive development of pre-adult females at 18 days post infection (dpi) from mixed infections and at 50 dpi from unisexual infections of laboratory mice in basic medium RPMI-1640. We found RBCs, rather than other nutrients, promoted the female sexual maturation and egg production with significant morphological changes. In 27% of females (18 dpi) from mixed infections that paired with males in vitro on day 14, vitelline glands could be positively stained by Fast Blue B; and in 35% of females (50 dpi) from unisexual infections on day 21, mature vitelline cells were observed. Infertile eggs were detected among both groups. To analyze which component of mouse RBCs possesses the stimulating effect, RBCs were fractionated and included in media. However, the RBC fractions failed to stimulate development of the female reproductive organs. In addition, bovine hemoglobin hydrolysate, digested by neutral protease, was found to exhibit the promoting activity instead of untreated bovine hemoglobin. The other protein hydrolysate, lactalbumin hydrolysate, exhibited a similar effect with bovine hemoglobin hydrolysate. Using quantitative RT-PCR, we found the expression levels of four reproduction-related genes were significantly stimulated by RBCs. These data indicate that RBCs provide essential nutrients for the sexual maturation of female S. japonicum and that the protein component of RBCs appeared to constitute the key nutrient. These findings would improve laboratory culture of pre-adult schistosomes to adult worms in medium with well-defined components

  9. Intake of Erythrocytes Required for Reproductive Development of Female Schistosoma japonicum

    PubMed Central

    Wang, Jipeng; Wang, Shuqi; Liu, Xiufeng; Xu, Bin; Chai, Riyi; Zhou, Pan; Ju, Chuan; Sun, Jun; Brindley, Paul J.; Hu, Wei

    2015-01-01

    The reproductive development and maturation of female schistosomes are crucial since their released eggs are responsible for the host immunopathology and transmission of schistosomiasis. However, little is known about the nutrients required by female Schistosoma japonicum during its sexual maturation. We evaluated the promoting effect of several nutrients (calf serum, red blood cells (RBCs), ATP and hypoxanthine) on the reproductive development of pre-adult females at 18 days post infection (dpi) from mixed infections and at 50 dpi from unisexual infections of laboratory mice in basic medium RPMI-1640. We found RBCs, rather than other nutrients, promoted the female sexual maturation and egg production with significant morphological changes. In 27% of females (18 dpi) from mixed infections that paired with males in vitro on day 14, vitelline glands could be positively stained by Fast Blue B; and in 35% of females (50 dpi) from unisexual infections on day 21, mature vitelline cells were observed. Infertile eggs were detected among both groups. To analyze which component of mouse RBCs possesses the stimulating effect, RBCs were fractionated and included in media. However, the RBC fractions failed to stimulate development of the female reproductive organs. In addition, bovine hemoglobin hydrolysate, digested by neutral protease, was found to exhibit the promoting activity instead of untreated bovine hemoglobin. The other protein hydrolysate, lactalbumin hydrolysate, exhibited a similar effect with bovine hemoglobin hydrolysate. Using quantitative RT-PCR, we found the expression levels of four reproduction-related genes were significantly stimulated by RBCs. These data indicate that RBCs provide essential nutrients for the sexual maturation of female S. japonicum and that the protein component of RBCs appeared to constitute the key nutrient. These findings would improve laboratory culture of pre-adult schistosomes to adult worms in medium with well-defined components

  10. Age-dependent differences in nicotine reward and withdrawal in female mice.

    PubMed

    Kota, D; Martin, B R; Damaj, M I

    2008-06-01

    Adolescent smoking is an increasing epidemic in the US. Research has shown that the commencement of smoking at a young age increases addiction and decreases the probability of successful cessation; however, limited work has focused on nicotine dependence in the female. The goal of the present study was to identify the biological and behavioral factors that may contribute to nicotine's increased abuse liability in female adolescents using animal models of nicotine dependence. Early adolescent (PND 28) and adult (PND 70) female mice were compared in various aspects of nicotine dependence using reward and withdrawal models following sub-chronic nicotine exposure. Furthermore, in vivo acute sensitivity and tolerance to nicotine were examined. In the conditioned place preference model, adolescents demonstrated a significant preference at 0.5 mg/kg nicotine, an inactive dose in adults. Adults found higher doses (0.7 and 1.0 mg/kg) of nicotine to elicit rewarding effects. Furthermore, adolescents displayed increased physical, but not affective, withdrawal signs in three models. Upon acute exposure to nicotine, adolescent mice showed increased sensitivity in an analgesic measure as well as hypothermia. After chronic nicotine exposure, both adults and adolescents displayed tolerance to nicotine with adolescents having a lower degree of tolerance to changes in body temperature. These data indicate that differences in nicotine's rewarding and aversive effects may contribute to variations in certain components of nicotine dependence between adult and adolescent female mice. Furthermore, this implies that smoking cessation therapies may not be equally effective across all ages.

  11. Genetic and environmental influences on female sexual orientation, childhood gender typicality and adult gender identity.

    PubMed

    Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

    2011-01-01

    Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates--childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation.

  12. Women Reading for Education, Affinity & Development (WREAD): An Evaluation of a Semistructured Reading Discussion Group for African American Female Adult-Literacy Students with Histories of Trauma

    ERIC Educational Resources Information Center

    Jones, Jayatta D.

    2012-01-01

    Women Reading for Education, Affinity & Development (WREAD), a reading discussion group geared toward African American female adult-literacy students with self-defined histories of trauma, was an outgrowth of research identifying links between trauma, women's struggles with literacy, and the need to be conscious of emotional health…

  13. Masculine Female Adolescents at School

    ERIC Educational Resources Information Center

    Ma'ayan, Hadar Dubowsky

    2003-01-01

    The current literatures on girls, queer youth, and multicultural education have ignored a significant group of young people and their experiences in school. This research is a retrospective exploratory study of masculine female adolescent schooling experiences, focusing on the school experiences of adults aged 18-54 who were socially defined as…

  14. Changes in lean and skeletal muscle body mass in adult females with anorexia nervosa before and after weight restoration.

    PubMed

    El Ghoch, Marwan; Pourhassan, Maryam; Milanese, Chiara; Müller, Manfred J; Calugi, Simona; Bazzani, Paola Vittoria; Dalle Grave, Riccardo

    2017-02-01

    Data on the deficits in lean body mass (LBM) and total body skeletal muscle mass (SM) in anorexia nervosa (AN) is scarce and inconsistent. Furthermore, the usefulness of the reported body mass index (BMI) severity cut-off for AN has not been tested with respect to these important parameters. The study had two aims, namely to study LBM patterns and SM in adult females with AN before and after weight restoration, and to examine the clinical usefulness of the 16.5 kg/m 2 BMI cut-off for assessing the protein status in terms of LBM and SM in AN patients. Body composition was measured by dual-energy X-ray absorptiometry (DXA) before and after weight gain in 90 adult female inpatients with AN, and 90 controls matched by post-treatment BMI and age. Patients were stratified into two groups using BMI 16.5 kg/m 2 as a cut-off. Before weight restoration, patients in the BMI≤16.5 kg/m 2 subgroup (n = 65) had lower LBM, SM and lean extremity mass percentage, but higher %LBM and lean trunk-to-extremity ratio on average than controls. However, those with BMI >16.5 kg/m 2 (n = 25) displayed lower lean extremity mass percentage and higher %LBM, but no significant differences in LBM and SM with respect to controls. Moreover the time × subgroup interaction was significant in terms of LBM and SM, meaning that, changes occur in different manner over time in the two AN subgroups. However no differences were found between the two AN subgroups in either demographic or other eating disorder characteristics. After weight gain, normalization of LBM, %LBM, lean extremity mass percentage and SM was achieved across the entire AN sample, and the BMI≤16.5 kg/m 2 subgroup. The fat mass was the major determinant of gain in LBM; the higher the FM at baseline, the greater the increase in LBM. Our results suggest a BMI cut-off ≤16.5 kg/m 2 as a clinical threshold for determining AN severity. As short-term weight restoration is associated with a normalization in LBM and SM, it

  15. Polyandrous females found fitter populations.

    PubMed

    Power, D J; Holman, L

    2014-09-01

    Multiple mating by females (polyandry) requires an evolutionary explanation, because it carries fitness costs in many species. When mated females disperse alone to a new habitat, their offspring may have no option but to mate with their siblings and incur inbreeding depression. However, some of the offspring of polyandrous females may only be half siblings, reducing inbreeding depression when isolated groups of siblings only have each other as mates. We investigated this putative benefit of polyandry over monandry by initiating multiple genetically isolated populations of Callosobruchus maculatus beetles, each founded by a single female, who received a complete ejaculate from either one or two males. The early generations had comparable fitness, but the F4 and F5 descendants of doubly inseminated females were more numerous and had higher egg-to-adult survival than the descendants of singly inseminated females. This fitness benefit was of similar magnitude whether beetles were reared on their standard food plant, or on a less favourable food source. Our results suggest that polyandrous females produce fitter descendants in inbred founder populations and therefore that polyandry may affect movement ecology and invasion biology. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  16. Susceptibility of adult female Aedes aegypti (Diptera: Culicidae) to the entomopathogenic fungus Metarhizium anisopliae is modified following blood feeding.

    PubMed

    Paula, Adriano R; Carolino, Aline T; Silva, Carlos P; Samuels, Richard I

    2011-05-26

    The mosquito Aedes aegypti, vector of dengue fever, is a target for control by entomopathogenic fungi. Recent studies by our group have shown the susceptibility of adult A. aegypti to fungal infection by Metarhizium anisopliae. This fungus is currently being tested under field conditions. However, it is unknown whether blood-fed A. aegypti females are equally susceptible to infection by entomopathogenic fungi as sucrose fed females. Insect populations will be composed of females in a range of nutritional states. The fungus should be equally efficient at reducing survival of insects that rest on fungus impregnated surfaces following a blood meal as those coming into contact with fungi before host feeding. This could be an important factor when considering the behavior of A. aegypti females that can blood feed on multiple hosts over a short time period. Female A. aegypti of the Rockefeller strain and a wild strain were infected with two isolates of the entomopathogenic fungus M. anisopliae (LPP 133 and ESALQ 818) using an indirect contact bioassay at different times following blood feeding. Survival rates were monitored on a daily basis and one-way analysis of variance combined with Duncan's post-hoc test or Log-rank survival curve analysis were used for statistical comparisons of susceptibility to infection. Blood feeding rapidly reduced susceptibility to infection, determined by the difference in survival rates and survival curves, when females were exposed to either of the two M. anisopliae isolates. Following a time lag which probably coincided with digestion of the blood meal (96-120 h post-feeding), host susceptibility to infection returned to pre-blood fed (sucrose fed) levels. Reduced susceptibility of A. aegypti to fungi following a blood meal is of concern. Furthermore, engorged females seeking out intra-domicile resting places post-blood feeding, would be predicted to rest for prolonged periods on fungus impregnated black cloths, thus optimizing infection

  17. Adolescent chronic restraint stress (aCRS) elicits robust depressive-like behavior in freely cycling, adult female rats without increasing anxiety-like behaviors.

    PubMed

    Hibicke, Meghan; Graham, Martha A; Hayslett, Renée L

    2017-04-01

    Stress during times of rapid development is a risk factor for Major Depressive Disorder, a mood disorder that disproportionately affects women. We developed an adolescent chronic restraint stress (aCRS) protocol using female rats to address the impact of adolescent stress on female adult depressive-like behavior. Animals were divided into 4 treatment groups: not restrained:saline (NRSAL), not restrained:desipramine (NRDES), restrained:saline (RSAL), and restrained:desipramine (RDES). NRSAL and NRDES rats were housed in a separate colony room from RSAL and RDES rats. All animals were weighed and handled daily. Beginning postnatal day (PND) 34(±1), RSAL and RDES rats were restrained for 1 hour daily for 14 consecutive days. Beginning PND 55(±1), NRDES and RDES rats were given subcutaneous desipramine (5 mg/kg), which served as a positive control, daily for 14 consecutive days. During that same time period, NRSAL and RSAL rats were given subcutaneous saline daily. aCRS (RSAL and RDES) rats showed significantly attenuated weight gain compared with nonrestrained (NRSAL and NRDES) rats during the restraint period. Weight gain normalized after the final restraint session. Behavioral testing took place PND 68-69(±1), and included open field testing, the elevated plus maze, locomotor activity, and the forced swim test (FST). RSAL rats showed significantly more immobility in the FST versus all other groups, indicating depressive-like behavior. No differences between groups were observed in the other behavioral measures. These results indicate that aCRS elicits depressive-like behavioral characteristics in adult female rats without increasing anxiety-like behaviors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Diving Behaviors and Habitat Use of Adult Female Steller Sea Lion (Eumetopias jubatus), A Top Predator of the Bering Sea and North Pacific Ocean Ecosystems

    NASA Astrophysics Data System (ADS)

    Lander, M. E.; Fadely, B.; Gelatt, T.; Sterling, J.; Johnson, D.; Haulena, M.; McDermott, S.

    2016-02-01

    Decreased natality resulting from nutritional stress is one hypothesized mechanism for declines of Steller sea lions (SSLs; Eumetopias jubatus) in western Alaska, but little is known of the winter foraging habitats or behavior of adult females. To address this critical data need, adult female Steller sea lions were chemically immobilized and tagged with Fastloc® GPS satellite transmitters during the fall at Southeast Alaska (SEAK) during 2010 (n=3), and the central and western Aleutian Islands (AI) from 2011-2014 (n=9). To identify habitat features of biological importance to these animals, location data were processed with a continuous-time correlated random walk model and kernel density estimates of predicted locations were used to compute individual-based utilization distributions. Kernel density estimates and diving behaviors (i.e. mean, maximum, and frequency of dive depths) were examined with respect to a series of static and dynamic environmental variables using linear mixed-effects models. Habitat use varied within and among individuals, but overall, all response variables were significantly related to a combination of the predictor variables season, distance to nearest SSL site, bathymetric slope, on/off shelf, sea surface temperature, sea surface height, proportion of daylight, and some interaction effects (P≤0.05). The habitat use of SSL from SEAK was consistent with previous reports and reflected the seasonal distribution of predictable forage fish, whereas SSL from the AI used a variety of marine ecosystems and habitat use was more variable, likely reflecting specific prey behaviors encountered in different areas. These results have improved our understanding of the habitat features necessary for the conservation of adult female SSL and have been useful for reviewing designated critical habitat for Steller sea lions throughout the U.S. range.

  19. A DNA vaccine delivered by dermal electroporation fully protects cynomolgus macaques against Lassa fever.

    PubMed

    Cashman, Kathleen A; Wilkinson, Eric R; Shaia, Carl I; Facemire, Paul R; Bell, Todd M; Bearss, Jeremy J; Shamblin, Joshua D; Wollen, Suzanne E; Broderick, Kate E; Sardesai, Niranjan Y; Schmaljohn, Connie S

    2017-12-02

    Lassa virus (LASV) is an ambisense RNA virus in the Arenaviridae family and is the etiological agent of Lassa fever, a severe hemorrhagic disease endemic to West and Central Africa. 1,2 There are no US Food and Drug Administration (FDA)-licensed vaccines available to prevent Lassa fever. 1,2 in our previous studies, we developed a gene-optimized DNA vaccine that encodes the glycoprotein precursor gene of LASV (Josiah strain) and demonstrated that 3 vaccinations accompanied by dermal electroporation protected guinea pigs from LASV-associated illness and death. Here, we describe an initial efficacy experiment in cynomolgus macaque nonhuman primates (NHPs) in which we followed an identical 3-dose vaccine schedule that was successful in guinea pigs, and a follow-on experiment in which we used an accelerated vaccination strategy consisting of 2 administrations, spaced 4 weeks apart. In both studies, all of the LASV DNA-vaccinated NHPs survived challenge and none of them had measureable, sustained viremia or displayed weight loss or other disease signs post-exposure. Three of 10 mock-vaccinates survived exposure to LASV, but all of them became acutely ill post-exposure and remained chronically ill to the study end point (45 d post-exposure). Two of the 3 survivors experienced sensorineural hearing loss (described elsewhere). These results clearly demonstrate that the LASV DNA vaccine combined with dermal electroporation is a highly effective candidate for eventual use in humans.

  20. Longitudinal analysis of the group A Streptococcus transcriptome in experimental pharyngitis in cynomolgus macaques.

    PubMed

    Virtaneva, Kimmo; Porcella, Stephen F; Graham, Morag R; Ireland, Robin M; Johnson, Claire A; Ricklefs, Stacy M; Babar, Imran; Parkins, Larye D; Romero, Romina A; Corn, G Judson; Gardner, Don J; Bailey, John R; Parnell, Michael J; Musser, James M

    2005-06-21

    Identification of the genetic events that contribute to host-pathogen interactions is important for understanding the natural history of infectious diseases and developing therapeutics. Transcriptome studies conducted on pathogens have been central to this goal in recent years. However, most of these investigations have focused on specific end points or disease phases, rather than analysis of the entire time course of infection. To gain a more complete understanding of how bacterial gene expression changes over time in a primate host, the transcriptome of group A Streptococcus (GAS) was analyzed during an 86-day infection protocol in 20 cynomolgus macaques with experimental pharyngitis. The study used 260 custom Affymetrix (Santa Clara, CA) chips, and data were confirmed by TaqMan analysis. Colonization, acute, and asymptomatic phases of disease were identified. Successful colonization and severe inflammation were significantly correlated with an early onset of superantigen gene expression. The differential expression of two-component regulators covR and spy0680 (M1_spy0874) was significantly associated with GAS colony-forming units, inflammation, and phases of disease. Prophage virulence gene expression and prophage induction occurred predominantly during high pathogen cell densities and acute inflammation. We discovered that temporal changes in the GAS transcriptome were integrally linked to the phase of clinical disease and host-defense response. Knowledge of the gene expression patterns characterizing each phase of pathogen-host interaction provides avenues for targeted investigation of proven and putative virulence factors and genes of unknown function and will assist vaccine research.

  1. Reversal of prenatal morphine exposure-induced memory deficit in male but not female rats.

    PubMed

    Nasiraei-Moghadam, Shiva; Sherafat, Mohammad Amin; Safari, Mir-Shahram; Moradi, Fatemeh; Ahmadiani, Abolhassan; Dargahi, Leila

    2013-05-01

    Impaired memory performance in offspring is one of the long-lasting neurobehavioral consequences of prenatal opiate exposure. Here, we studied the effects of prenatal morphine exposure on inhibitory avoidance memory performance in male and female offspring and also investigated whether these deficits are reversible during the postnatal development. Pregnant Wistar rats received morphine sulfate through drinking water, from the first day of gestation up to the day 13, M₁₋₁₃, or to the time of delivery, M₁₋₂₁. Four- and ten-week-old (adolescent and adult, respectively) male and female offspring were subjected to behavioral assays and then analysis of proteins involved in apoptosis or in synaptic plasticity. Results revealed that adolescent and adult female rats failed in passive avoidance retention task in both M₁₋₁₃ and M₁₋₂₁ groups. Adolescent and adult male offspring were similar to control animals in M₁₋₁₃ group. However M₁₋₂₁ impaired retention task in prepubertal male offspring, and this memory loss was repaired in postpubertal stage. Consistently, Bax/Bcl-2 ratio and cleaved caspase-3 were significantly increased in both M₁₋₁₃ and M₁₋₂₁ adolescent and adult female rats, but only in M₁₋₂₁ adolescent male rats. Furthermore, prenatal morphine exposure reduced the expression of brain-derived neurotrophic factor precursor protein in adolescent and adult female offspring and also decreased p-ca(2+)/calmodulin-dependent kinase II/ca(2+)/calmodulin-dependent kinase II ratio in adolescent male and female rats. Altogether, the results show that prenatal morphine exposure, depending on the time or duration of exposure, has distinct effects on male and female rats, and postnatal development may reverse these deficits more likely in males.

  2. IND-directed safety and biodistribution study of intravenously injected cetuximab-IRDye800 in cynomolgus macaques.

    PubMed

    Zinn, Kurt R; Korb, Melissa; Samuel, Sharon; Warram, Jason M; Dion, David; Killingsworth, Cheryl; Fan, Jinda; Schoeb, Trenton; Strong, Theresa V; Rosenthal, Eben L

    2015-02-01

    The use of receptor-targeted antibodies conjugated to fluorophores is actively being explored for real-time imaging of disease states; however, the toxicity of the bioconjugate has not been assessed in non-human primates. To this end, the in vivo toxicity and pharmacokinetics of IRDye800 conjugated to cetuximab (cetuximab-IRDye800; 21 mg/kg; equivalent to 250 mg/m(2) human dose) were assessed in male cynomolgus monkeys over 15 days following intravenous injection and compared with an unlabeled cetuximab-dosed control group. Cetuximab-IRDye800 was well tolerated. There were no infusion reactions, adverse clinical signs, mortality, weight loss, or clinical histopathology findings. The plasma half-life for the cetuximab-IRDye800 and cetuximab groups was equivalent (2.5 days). The total recovered cetuximab-IRDye800 in all tissues at study termination was estimated to be 12 % of the total dose. Both cetuximab-IRDye800 and cetuximab groups showed increased QTc after dosing. The QTc for the cetuximab-dosed group returned to baseline by day 15, while the QTc of the cetuximab-IRDye800 remained elevated compared to baseline. IRDye800 in low molar ratios does not significantly impact cetuximab half-life or result in organ toxicity. These studies support careful cardiac monitoring (ECG) for human studies using fluorescent dyes.

  3. Age and adolescent social stress effects on fear extinction in female rats.

    PubMed

    McCormick, C M; Mongillo, D L; Simone, J J

    2013-11-01

    We previously observed that social instability stress (SS: daily 1 h isolation and change of cage partners for 16 days) in adolescence, but not in adulthood, decreased context and cue memory after fear conditioning in male rats. Effects of stress are typically sex-specific, and so here we investigated adolescent and adult SS effects in females on the strength of acquired contextual and cued fear conditioning, as well as extinction learning, beginning either the day after the stress procedure or four weeks later. For SS in adolescence, SS females spent more time freezing (fear measure) during extinction than did controls, whereas SS in adulthood had no effect on any measure of fear conditioning. The results also indicated an effect of age: females in late adolescence show more rapid extinction of cue and better memory of extinction of context compared to adult females, which may indicate resilience to acute footshock in adolescence. Thus fear circuitry continues to mature into late adolescence, which may underlie the heightened plasticity in response to chronic stressors of adolescents compared to adults.

  4. Hormone suppression with GnRH antagonist promotes spermatogenic recovery from transplanted spermatogonial stem cells in irradiated cynomolgus monkeys.

    PubMed

    Shetty, G; Uthamanthil, R K; Zhou, W; Shao, S H; Weng, C C; Tailor, R C; Hermann, B P; Orwig, K E; Meistrich, M L

    2013-11-01

    Hormone suppression given before or after cytotoxic treatment stimulates the recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (SSC) and restores fertility in rodents. To test whether the combination of hormone suppression and transplantation could enhance the recovery of spermatogenesis in primates, we irradiated (7 Gy) the testes of 12 adult cynomolgus monkeys and treated six of them with gonadotropin-releasing hormone antagonist (GnRH-ant) for 8 weeks. At the end of this treatment, we transfected cryopreserved testicular cells with green fluorescent protein-lentivirus and autologously transplanted them back into one of the testes. The only significant effect of GnRH-ant treatment on endogenous spermatogenesis was an increase in the percentage of tubules containing differentiated germ cells (tubule differentiation index; TDI) in the sham-transplanted testes of GnRH-ant-treated monkeys compared with radiation-only monkeys at 24 weeks after irradiation. Although transplantation alone after irradiation did not significantly increase the TDI, detection of lentiviral DNA in the spermatozoa of one radiation-only monkey indicated that some transplanted cells colonized the testis. However, the combination of transplantation and GnRH-ant clearly stimulated spermatogenic recovery as evidenced by several observations in the GnRH-ant-treated monkeys receiving transplantation: (i) significant increases (~20%) in the volume and weight of the testes compared with the contralateral sham-transplanted testes and/or to the transplanted testes of the radiation-only monkeys; (ii) increases in TDI compared to the transplanted testes of radiation-only monkeys at 24 weeks (9.6% vs. 2.9%; p = 0.05) and 44 weeks (16.5% vs. 6.1%, p = 0.055); (iii) detection of lentiviral sequences in the spermatozoa or testes of five of the GnRH-ant-treated monkeys and (iv) significantly higher sperm counts than in the radiation-only monkeys. Thus hormone

  5. Attractiveness Modulates Neural Processing of Infant Faces Differently in Males and Females.

    PubMed

    Yin, Lijun; Fan, Mingxia; Lin, Lijia; Sun, Delin; Wang, Zhaoxin

    2017-01-01

    Consistent attention and proper processing of infant faces by adults are essential for infant survival. Previous behavioral studies showed gender differences in processing infant cues (e.g., crying, laughing or facial attractiveness) and more importantly, the efforts invested in nurturing offspring. The underlying neural mechanisms of processing unknown infant faces provide hints for understanding behavioral differences. This functional magnetic resonance imaging (fMRI) study recruited 32 unmarried adult (16 females and 16 males) participants to view unfamiliar infant faces and rate the attractiveness. Adult faces were also included. Behaviorally, despite that females and males showed no differences in attractiveness ratings of infant faces, a positive correlation was found between female's (but not male's) subjective liking for infants and attractiveness ratings of the infant faces. Functionally, brain activations to infant faces were modulated by attractiveness differently in males and females. Specifically, in female participants, activities in the ventromedial prefrontal cortex (vmPFC) and striatum/Nucleus Accumbens (NAcc) were positively modulated by infant facial attractiveness, and the modulation coefficients of these two regions were positively correlated. In male participants, infant facial attractiveness negatively modulated the activity in the dorsomedial prefrontal cortex (dmPFC). Our findings reveal that different neural mechanisms are involved in the processing of infant faces, which might lead to observed behavioral differences between males and females towards the baby.

  6. Reactions to First Postpubertal Female Same-Sex Sexual Experience in the Kinsey Sample: A Comparison of Minors with Peers, Minors with Adults, and Adults with Adults.

    PubMed

    Rind, Bruce

    2017-07-01

    This study examined reactions to first postpubertal same-sex sexual experience in the Kinsey female same-sex sample (consisting of females with extensive postpubertal same-sex experience) as a function of participant and partner ages. As such, it complemented the Rind and Welter (2016) study, which examined the same in the Kinsey male same-sex sample. Data were collected by Kinsey interviewers between 1939 and 1961 (M year = 1947). Girls under 18 (M age = 14.9), whose sexual experience was with a woman (M age = 26.3), reacted positively just as often as girls under 18 (M age = 14.1) with peers (M age = 15.0) and women (M age = 22.7) with women (M age = 26.3). The positive-reaction rates were, respectively, 85, 82, and 79 %. In a finer-graded analysis, younger adolescent girls (≤14) (M age = 12.8) with women (M age = 27.4) had a high positive-reaction rate (91 %), a rate reached by no other group. For women (M age = 22.2) with same-aged peers (M age = 22.3), this rate was 86 %. Girls with peers or women had no emotionally negative reactions (e.g., fear, disgust, shame, regret); women with women rarely did. Results contradicted prevailing clinical, legal, and lay beliefs that minor-adult sex is inherently traumatic and would be distinguished as such compared to age-concordant sex. The findings are discussed in terms of the time period in which the sexual experiences occurred.

  7. Sex-role reversal of a monogamous pipefish without higher potential reproductive rate in females.

    PubMed

    Sogabe, Atsushi; Yanagisawa, Yasunobu

    2007-12-07

    In monogamous animals, males are usually the predominant competitors for mates. However, a strictly monogamous pipefish Corythoichthys haematopterus exceptionally exhibits a reversed sex role. To understand why its sex role is reversed, we measured the adult sex ratio and the potential reproductive rate (PRR), two principal factors influencing the operational sex ratio (OSR), in a natural population of southern Japan. The adult sex ratio was biased towards females throughout the breeding season, but the PRR, which increased with water temperature, did not show sexual difference. We found that an alternative index of the OSR (Sf/Sm: sex ratio of 'time in') calculated from the monthly data was consistently biased towards females. The female-biased OSR associated with sex-role reversal has been reported in some polyandrous or promiscuous pipefish, but factors biasing the OSR differed between these pipefish and C. haematopterus. We concluded that the similar PRR between the sexes in C. haematopterus does not confer reproductive benefit of polygamous mating on either sex, resulting in strict monogamous mating, and its female-biased adult sex ratio promotes female-female competition for a mate, resulting in sex-role reversal.

  8. Pharmacokinetics and pharmacodynamics of injectable testosterone undecanoate in castrated cynomolgus monkeys (Macaca fascicularis) are independent of different oil vehicles.

    PubMed

    Wistuba, Joachim; Marc Luetjens, C; Kamischke, Axel; Gu, Yi-Qun; Schlatt, Stefan; Simoni, Manuela; Nieschlag, Eberhard

    2005-08-01

    Testosterone undecanoate (TU) dissolved in soybean oil was developed in China to improve the pharmacokinetics of this testosterone ester in comparison with TU in castor or tea seed oil. As a pre-clinical primate model, three groups of five castrated cynomolgus macaques received either a single intramuscular injection of 10 mg/kg body weight TU in soybean oil, in tea seed oil, or in castor oil (equals 6.3 mg pure T/kg body weight for all preparations). Testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone as well as prostate volume, body weight and ejaculate weight were evaluated. After injection supraphysiological testosterone levels were induced. There were no significant differences in the pharmacokinetics of the three TU preparations for testosterone and estradiol. The gonadotropin levels showed a high individual variation. Prostate volumes increased equally in all groups after administration and declined to castrate level afterwards. The results suggest that TU in soybean oil produces similar effects as TU in the other vehicles. This study in non-human primates provides no objection to testing of this new preparation in humans.

  9. A 52-week safety study in cynomolgus macaques for genetically modified rice expressing Cry1Ab/1Ac protein.

    PubMed

    Mao, Jie; Sun, Xing; Cheng, Jian-Hua; Shi, Yong-Jie; Wang, Xin-Zheng; Qin, Jun-Jie; Sang, Zhi-Hong; He, Kun; Xia, Qing

    2016-09-01

    A 52-week feeding study in cynomolgus macaques was carried out to evaluate the safety of Bt rice Huahui 1 (HH1), a transgenic rice line expressing Cry1Ab/1Ac protein. Monkeys were fed a diet with 20% or 60% HH1 rice, 20% or 60% parental rice (Minghui 63, MH63), normal diet, normal diet spiked with purified recombinant Cry1Ab/1Ac fusion protein or bovine serum albumin (BSA) respectively. During the feeding trail, clinical observations were conducted daily, and multiple parameters, including body weight, body temperature, electrocardiogram, hematology, blood biochemistry, serum metabolome and gut microbiome were examined at regular intervals. Upon sacrifice, the organs were weighted, and the macroscopic, microscopic and electron microscopic examinations were performed. The results show no adverse or toxic effects of Bt rice HH1 or Cry1Ab/1Ac fusion protein on monkeys. Therefore, the present 52-week primate feeding study suggests that the transgenic rice containing Cry 1Ab/1Ac is equivalent to its parental rice line MH63. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. A global research synthesis of HIV and STI biobehavioral risks in female-to-male (FTM) transgender adults

    PubMed Central

    Reisner, Sari L.; Murchison, Gabriel R.

    2016-01-01

    There is a growing interest in HIV infection and sexually transmitted infection (STI) disease burden and risk among transgender people globally; however, the majority of work has been conducted with male-to-female (MTF) transgender populations. This research synthesis comprehensively reviews HIV and STI research in female-to-male (FTM) transgender adults. A paucity of research exists about HIV and STIs in FTMs. Only 25 peer-reviewed papers (18 quantitative, 7 qualitative) and 11 ‘grey literature’ reports were identified, most in the U.S. or Canada, that include data identifying HIV and STI risks in FTMs (five with fully laboratory-confirmed HIV and/or STIs, and five with partial laboratory confirmation). Little is known about the sexual and drug use risk behaviors contributing to HIV and STIs in FTMs. Future directions are suggested, including the need for routine surveillance and monitoring of HIV and STIs globally by transgender identity, more standardized sexual risk assessment measures, targeted data collection in lower and middle income countries, and explicit consideration of the rationale for inclusion/exclusion of FTMs in category-based prevention approaches with MSM and transgender people. Implications for research, policy, programming, and interventions are discussed, including the need to address diverse sexual identities, attractions, and behaviors and engage local FTM communities. PMID:26785800

  11. Acoustic analysis of normal Saudi adult voices.

    PubMed

    Malki, Khalid H; Al-Habib, Salman F; Hagr, Abulrahman A; Farahat, Mohamed M

    2009-08-01

    To determine the acoustic differences between Saudi adult male and female voices, and to compare the acoustic variables of the Multidimensional Voice Program (MDVP) obtained from North American adults to a group of Saudi males and females. A cross-sectional survey of normal adult male and female voices was conducted at King Abdulaziz University Hospital, Riyadh, Kingdom of Saudi Arabia between March 2007 and December 2008. Ninety-five Saudi subjects sustained the vowel /a/ 6 times, and the steady state portion of 3 samples was analyzed and compared with the samples of the KayPentax normative voice database. Significant differences were found between Saudi and North American KayPentax database groups. In the male subjects, 15 of 33 MDVP variables, and 10 of 33 variables in the female subjects were found to be significantly different from the KayPentax database. We conclude that the acoustical differences may reflect laryngeal anatomical or tissue differences between the Saudi and the KayPentax database.

  12. Black Females in High School: A Statistical Educational Profile

    ERIC Educational Resources Information Center

    Muhammad, Crystal Gafford; Dixson, Adrienne D.

    2008-01-01

    In life as in literature, both the mainstream public and the Black community writ large, overlook the Black female experiences, both adolescent and adult. In order to contribute to the knowledge base regarding this population, we present through our study a statistical portrait of Black females in high school. To do so, we present an analysis of…

  13. LC-MS/MS quantification of next-generation biotherapeutics: a case study for an IgE binding Nanobody in cynomolgus monkey plasma.

    PubMed

    Sandra, Koen; Mortier, Kjell; Jorge, Lucie; Perez, Luis C; Sandra, Pat; Priem, Sofie; Poelmans, Sofie; Bouche, Marie-Paule

    2014-05-01

    Nanobodies(®) are therapeutic proteins derived from the smallest functional fragments of heavy chain-only antibodies. The development and validation of an LC-MS/MS-based method for the quantification of an IgE binding Nanobody in cynomolgus monkey plasma is presented. Nanobody quantification was performed making use of a proteotypic tryptic peptide chromatographically enriched prior to LC-MS/MS analysis. The validated LLOQ at 36 ng/ml was measured with an intra- and inter-assay precision and accuracy <20%. The required sensitivity could be obtained based on the selectivity of 2D LC combined with MS/MS. No analyte specific tools for affinity purification were used. Plasma samples originating from a PK/PD study were analyzed and compared with the results obtained with a traditional ligand-binding assay. Excellent correlations between the two techniques were obtained, and similar PK parameters were estimated. A 2D LC-MS/MS method was successfully developed and validated for the quantification of a next generation biotherapeutic.

  14. Genetic and Environmental Influences on Female Sexual Orientation, Childhood Gender Typicality and Adult Gender Identity

    PubMed Central

    Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

    2011-01-01

    Background Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Methodology/Principal Findings Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. Conclusions/Significance This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation. PMID:21760939

  15. Plasma vitamin D is associated with fasting insulin and HOMA-IR in young adult males, but not females, of the Jerusalem Perinatal Study

    PubMed Central

    Moore, Amy; Hochner, Hagit; Sitlani, Colleen M; Williams, Michelle A; Hoofnagle, Andrew N; de Boer, Ian H; Kestenbaum, Bryan; Siscovick, David S; Friedlander, Yechiel; Enquobahrie, Daniel A

    2015-01-01

    Objective To examine cross-sectional relationships between plasma vitamin D and Cardiometabolic Risk Factors in young adults. Design Data were collected from interviews, physical examinations, and biomarker measurements. Total plasma 25-hydroxyvitamin D (25[OH]D) was measured using liquid chromatography-tandem mass spectrometry. Associations between 25[OH]D and CMR were modeled using weighted linear regression with robust standard error estimates. Setting Individuals born in Jerusalem during 1974-1976. Subjects Participants of the Jerusalem Perinatal Study (n = 1,204) interviewed and examined at age 32 years. Participants were oversampled for low and high birthweight and for maternal pre-pregnancy obesity. Results Mean total 25[OH]D concentration among participants was 21.7 ng/mL (SD 8.9). Among males, 25[OH]D was associated with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (natural log-transformed, β = -0.011, p = 0.004) after adjustment for body mass index. However, these associations were not present among females (p for sex interaction = 0.005). Conclusions We found evidence for inverse associations of 25[OH]D with markers of insulin resistance among males, but not females, in a health, young adult Caucasian population. Prospective studies and studies conducted on other populations investigating sex specific effects of vitamin D on CMR are warranted. PMID:25145881

  16. Psychosexual Functioning Among Adult Female Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

    PubMed Central

    Ford, Jennifer S.; Kawashima, Toana; Whitton, John; Leisenring, Wendy; Laverdière, Caroline; Stovall, Marilyn; Zeltzer, Lonnie; Robison, Leslie L.; Sklar, Charles A.

    2014-01-01

    Purpose Childhood cancer survivors may be at risk for impaired psychosexual functioning as a direct result of their cancer or its treatments, psychosocial difficulties, and/or diminished quality of life. Patients and Methods Two thousand one hundred seventy-eight female adult survivors of childhood cancer and 408 female siblings from the Childhood Cancer Survivor Study (CCSS) completed a self-report questionnaire about their psychosexual functioning and quality of life. On average, participants were age 29 years (range, 18 to 51 years) at the time of the survey, had been diagnosed with cancer at a median age of 8.5 years (range, 0 to 20) and were most commonly diagnosed with leukemia (33.2%) and Hodgkin lymphoma (15.4%). Results Multivariable analyses suggested that after controlling for sociodemographic differences, survivors reported significantly lower sexual functioning (mean difference [MnD], −0.2; P = .01), lower sexual interest (MnD, −0.2; P < .01), lower sexual desire (MnD, −0.3; P < .01), lower sexual arousal (MnD, −0.3; P < .01), lower sexual satisfaction (MnD, −0.2; P = .01), and lower sexual activity (MnD, −0.1; P = .02) compared with siblings. Risk factors for poorer psychosexual functioning among survivors included older age at assessment, ovarian failure at a younger age, treatment with cranial radiation, and cancer diagnosis during adolescence. Conclusion Decreased sexual functioning among female survivors of childhood cancers seems to be unrelated to emotional factors and is likely to be an underaddressed issue. Several risk factors among survivors have been identified that assist in defining high-risk subgroups who may benefit from targeted screening and interventions. PMID:25113763

  17. Fitness consequences of larval exposure to Beauveria bassiana on adults of the malaria vector Anopheles stephensi.

    PubMed

    Vogels, Chantal B F; Bukhari, Tullu; Koenraadt, Constantianus J M

    2014-06-01

    Entomopathogenic fungi have shown to be effective in biological control of both larval and adult stages of malaria mosquitoes. However, a small fraction of mosquitoes is still able to emerge after treatment with fungus during the larval stage. It remains unclear whether fitness of these adults is affected by the treatment during the larval stage and whether they are still susceptible for another treatment during the adult stage. Therefore, we tested the effects of larval exposure to the entomopathogenic fungus Beauveria bassiana on fitness of surviving Anopheles stephensi females. Furthermore, we tested whether larval exposed females were still susceptible to re-exposure to the fungus during the adult stage. Sex ratio, survival and reproductive success were compared between non-exposed and larval exposed A. stephensi. Comparisons were also made between survival of non-exposed and larval exposed females that were re-exposed to B. bassiana during the adult stage. Larval treatment did not affect sex ratio of emerging mosquitoes. Larval exposed females that were infected died significantly faster and laid equal numbers of eggs from which equal numbers of larvae hatched, compared to non-exposed females. Larval exposed females that were uninfected had equal survival, but laid a significantly larger number of eggs from which a significantly higher number of larvae hatched, compared to non-exposed females. Larval exposed females which were re-exposed to B. bassiana during the adult stage had equal survival as females exposed only during the adult stage. Our results suggest that individual consequences for fitness of larval exposed females depended on whether a fungal infection was acquired during the larval stage. Larval exposed females remained susceptible to re-exposure with B. bassiana during the adult stage, indicating that larval and adult control of malaria mosquitoes with EF are compatible. Copyright © 2014. Published by Elsevier Inc.

  18. Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology.

    PubMed

    Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

    2004-07-01

    We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or 'depressive-like' symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild-type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the 'depressive-like' profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.

  19. Gender role across development in adults with 46,XY disorders of sex development including perineoscrotal hypospadias and small phallus raised male or female.

    PubMed

    Pappas, Kara B; Wisniewski, Amy B; Migeon, Claude J

    2008-07-01

    Self-rated degree of femininity and masculinity across development were evaluated for 40 adults affected by 46,XY disorders of sex development (DSDs) who presented at birth with a small phallus and perineoscrotal hypospadias, raised either male (n = 22) or female (n = 18). Most participants were confirmed or presumed to be affected by partial androgen insensitivity syndrome (n = 14), partial gonadal dysgenesis (n = 11), or were considered to have a poorly defined case of 46,XY DSD including ambiguous external genitalia (n = 15). Participants retrospectively evaluated their degree of masculinity and femininity during their childhood, adolescence, adulthood, and in the past 12 months of filling out a questionnaire pertaining to their psychosexual development. Participants raised male reported more masculinity than those raised female due to an increase in masculinization during adolescence and adulthood. Participants raised male also reported less femininity than those raised female throughout development. Participants raised female reported more femininity than those raised male due to an increase in feminization during adolescence and adulthood. Participants raised female also reported less masculinity than those raised male throughout development. These data support the proposition that some aspects of gender role (GR), such as masculinity and femininity, are capable of proceeding along female- or male-typic patterns depending on sex of rearing among individuals affected by specific types of 46,XY DSD. Furthermore, regardless of male or female rearing, GR increasingly corresponds with assigned sex as individuals proceed through sexual maturity and into adulthood. These results are consistent with the idea that socialization/learning contributes to GR development in humans in addition to data from others demonstrating endocrine influences.

  20. Fortuitous encounters between seagliders and adult female northern fur seals (Callorhinus ursinus) off the Washington (USA) coast: upper ocean variability and links to top predator behavior.

    PubMed

    Pelland, Noel A; Sterling, Jeremy T; Lea, Mary-Anne; Bond, Nicholas A; Ream, Rolf R; Lee, Craig M; Eriksen, Charles C

    2014-01-01

    Behavioral responses by top marine predators to oceanographic features such as eddies, river plumes, storms, and coastal topography suggest that biophysical interactions in these zones affect predators' prey, foraging behaviors, and potentially fitness. However, examining these pathways is challenged by the obstacles inherent in obtaining simultaneous observations of surface and subsurface environmental fields and predator behavior. In this study, migratory movements and, in some cases, diving behavior of 40 adult female northern fur seals (NFS; Callorhinus ursinus) were quantified across their range and compared to remotely-sensed environmental data in the Gulf of Alaska and California Current ecosystems, with a particular focus off the coast of Washington State (USA)--a known foraging ground for adult female NFS and where autonomous glider sampling allowed opportunistic comparison of seal behavior to subsurface biophysical measurements. The results show that in these ecosystems, adult female habitat utilization was concentrated near prominent coastal topographic, riverine, or inlet features and within 200 km of the continental shelf break. Seal dive depths, in most ecosystems, were moderated by surface light level (solar or lunar), mirroring known behaviors of diel vertically-migrating prey. However, seal dives differed in the California Current ecosystem due to a shift to more daytime diving concentrated at or below the surface mixed layer base. Seal movement models indicate behavioral responses to season, ecosystem, and surface wind speeds; individuals also responded to mesoscale eddies, jets, and the Columbia River plume. Foraging within small scale surface features is consistent with utilization of the inner coastal transition zone and habitats near coastal capes, which are known eddy and filament generation sites. These results contribute to our knowledge of NFS migratory patterns by demonstrating surface and subsurface behavioral responses to a spatially