X inactivation in Rett syndrome: A preliminary study showing partial preferential inactivation of paternal X with the M27{beta} probe

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

Camus, P.; Abbadi, N.; Gilgenkrantz, S.

1994-04-15

Rett syndrome (RS) is a severe progressive neurological disorder occurring exclusively in females. Most cases are sporadic. The few familial cases (less than 1%) cannot be explained by a simple mode of inheritance. Several hypotheses have been proposed: X-linked male lethal mutation, maternal uniparental disomy, fresh mutation on the X chromosome, involvement of mitochondrial DNA and differential inactivation with metabolic interference of X-borne alleles. The authors have examined the pattern of X inactivation in 10 affected girls who were selected according to the clinical criteria previously described and accepted by the French Rett Scientific Committee. The X inactivation pattern wasmore » studied by analysis of methylation at the hypervariable locus DXS255 with the M27{beta} probe. The results show a more-or-less skewed inactivation of paternal X in 8 Rett females, and 2 cases of symmetrical inactivation. In control girls, inactivation was symmetrical cases and the maternal X has been preferentially inactivated in the other 2 cases. In no case was a total skewed inactivation observed. Though there was clear evidence for a preferential paternal X inactivation that was statistically significant further studies are necessary to establish a relationship between X inactivation pattern and Rett syndrome.« less

Genetics Home Reference: Rett syndrome

MedlinePlus

... NC, Zappella M, Renieri A, Huppke P, Percy AK; RettSearch Consortium. Rett syndrome: revised diagnostic criteria and ... 2):118-28. Review. Citation on PubMed Percy AK, Lane JB. Rett syndrome: model of neurodevelopmental disorders. ...

An analogue assessment of repetitive hand behaviours in girls and young women with Rett syndrome.

PubMed

Wales, L; Charman, T; Mount, R H

2004-10-01

Rett syndrome is a neurodevelopmental disorder that almost exclusively affects females. In addition to neurodevelopmental regression and loss of hand skills, apraxia, deceleration of head growth, and increasing spasticity and scoliosis, a number of behavioural features are also seen, including stereotypic hand movements, hyperventilation and breath holding. The aim of the study was to investigate the extent to which analogue environmental conditions affected the frequency of repetitive hand behaviour in eight girls and young women with Rett syndrome. The frequency of repetitive hand movements was observed every 10 s for four 4-min sessions under the following conditions: Continuous Adult Attention, Adult Demands, Stimulation and No Stimulation. The frequency of repetitive hand movements was high -- they occurred in above 60% of all intervals in all conditions for all participants and at nearly 100% for some participants in some conditions. For one participant the frequency of repetitive hand movements was somewhat reduced in the Stimulation condition; for another it was relatively increased in the No Stimulation condition. Overall, environmental manipulations had relatively limited effects on repetitive hand behaviours. Repetitive hand behaviour in Rett syndrome may be maintained by automatic reinforcement or neurochemical processes and may not be primarily influenced by contingent reinforcement.

Prevalence and onset of comorbidities in the CDKL5 disorder differ from Rett syndrome.

PubMed

Mangatt, Meghana; Wong, Kingsley; Anderson, Barbara; Epstein, Amy; Hodgetts, Stuart; Leonard, Helen; Downs, Jenny

2016-04-14

Initially described as an early onset seizure variant of Rett syndrome, the CDKL5 disorder is now considered as an independent entity. However, little is currently known about the full spectrum of comorbidities that affect these patients and available literature is limited to small case series. This study aimed to use a large international sample to examine the prevalence in this disorder of comorbidities of epilepsy, gastrointestinal problems including feeding difficulties, sleep and respiratory problems and scoliosis and their relationships with age and genotype. Prevalence and onset were also compared with those occurring in Rett syndrome. Data for the CDKL5 disorder and Rett syndrome were sourced from the International CDKL5 Disorder Database (ICDD), InterRett and the Australian Rett syndrome Database (ARSD). Logistic regression (multivariate and univariate) was used to analyse the relationships between age group, mutation type and the prevalence of various comorbidities. Binary longitudinal data from the ARSD and the equivalent cross-sectional data from ICDD were examined using generalized linear models with generalized estimating equations. The Kaplan-Meier method was used to estimate the failure function for the two disorders and the log-rank test was used to compare the two functions. The likelihood of experiencing epilepsy, GI problems, respiratory problems, and scoliosis in the CDKL5 disorder increased with age and males were more vulnerable to respiratory and sleep problems than females. We did not identify any statistically significant relationships between mutation group and prevalence of comorbidities. Epilepsy, GI problems and sleep abnormalities were more common in the CDKL5 disorder than in Rett syndrome whilst scoliosis and respiratory problems were less prevalent. This study captured a much clearer picture of the CDKL5 disorder than previously possible using the largest sample available to date. There were differences in the presentation of

The Digestive System and Nutritional Considerations for Individuals with Rett Syndrome

PubMed Central

Lotan, Meir; Zysman, Lilit

2006-01-01

Rett syndrome (RS) is a neurodevelopmental syndrome of genetic origin that mainly affects females. Individuals diagnosed with RS exhibit a variety of functional difficulties that impair their quality of life. One of the affected systems is the digestive system, where 74% of persons with RS have abnormal functioning. The affected digestive system causes this population to present an array of problems, such as gastroesophageal reflux (GER), constipation, and malnutrition, leading to failure to thrive (FTT), which resolves in reduced functional ability. Due to the severe effects of the dysfunctional digestive system of individuals with RS, this article will describe the problems common to this population, as well as propose some clinical suggestions for intervention. . PMID:17195872

The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome.

PubMed

Schönewolf-Greulich, B; Tejada, M-I; Stephens, K; Hadzsiev, K; Gauthier, J; Brøndum-Nielsen, K; Pfundt, R; Ravn, K; Maortua, H; Gener, B; Martínez-Bouzas, C; Piton, A; Rouleau, G; Clayton-Smith, J; Kleefstra, T; Bisgaard, A-M; Tümer, Z

2016-06-01

Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rett syndrome and menstruation.

PubMed

Hamilton, Amy; Marshal, Michael P; Sucato, Gina S; Murray, Pamela J

2012-04-01

Describe the experience that girls with Rett syndrome have with menstruation including menstrual hygiene, dysmenorrhea, premenstrual syndrome (PMS), and attempts at treatment. Anonymous web-based survey. Convenience sample recruited from Rett syndrome LISTSERV in July of 2009. Mothers of girls with Rett syndrome between the ages of 10-25 who have had at least one menses. Prevalence, frequency, and severity of dysmenorrhea and PMS; hygiene concerns; and treatments attempts and perceived effectiveness. Dysmenorrhea and PMS are common problems among young women with Rett syndrome. Despite their frequency and severity they do not routinely limit activities. Multiple treatment attempts are common. Hormonal contraception is used mostly for menstrual cycle control with oral contraceptive pills the most commonly used method. Young women with Rett syndrome have standard symptoms of dysmenorrhea and PMS as well as autism spectrum specific PMS symptoms. Hormonal contraception is commonly used for menstrual management. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Reflex seizures in Rett syndrome.

PubMed

Roche Martínez, Ana; Alonso Colmenero, M Itziar; Gomes Pereira, Andreia; Sanmartí Vilaplana, Francesc X; Armstrong Morón, Judith; Pineda Marfa, Mercé

2011-12-01

Reflex seizures are a rare phenomenon among epileptic patients, in which an epileptic discharge is triggered by various kinds of stimuli (visual, auditory, tactile or gustatory). Epilepsy is common in Rett syndrome patients (up to 70%), but to the authors' knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.

Urinary Peptides in Rett Syndrome.

ERIC Educational Resources Information Center

Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

2002-01-01

A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

Rett syndrome and MeCP2.

PubMed

Liyanage, Vichithra R B; Rastegar, Mojgan

2014-06-01

Rett syndrome (RTT) is a severe and progressive neurological disorder, which mainly affects young females. Mutations of the methyl-CpG binding protein 2 (MECP2) gene are the most prevalent cause of classical RTT cases. MECP2 mutations or altered expression are also associated with a spectrum of neurodevelopmental disorders such as autism spectrum disorders with recent links to fetal alcohol spectrum disorders. Collectively, MeCP2 relation to these neurodevelopmental disorders highlights the importance of understanding the molecular mechanisms by which MeCP2 impacts brain development, mental conditions, and compromised brain function. Since MECP2 mutations were discovered to be the primary cause of RTT, a significant progress has been made in the MeCP2 research, with respect to the expression, function and regulation of MeCP2 in the brain and its contribution in RTT pathogenesis. To date, there have been intensive efforts in designing effective therapeutic strategies for RTT benefiting from mouse models and cells collected from RTT patients. Despite significant progress in MeCP2 research over the last few decades, there is still a knowledge gap between the in vitro and in vivo research findings and translating these findings into effective therapeutic interventions in human RTT patients. In this review, we will provide a synopsis of Rett syndrome as a severe neurological disorder and will discuss the role of MeCP2 in RTT pathophysiology.

Divorce in families of children with Down Syndrome or Rett Syndrome.

PubMed

Lederman, Vivian Renne Gerber; Alves, Bianca dos Santos; Negrão, Juliana; Maria, Juliana Negrão; Schwartzman, José Salomão; D'Antino, Maria Eloisa Famá; Brunoni, Decio

2015-05-01

This study evaluates the impact in the stability and management of the marriage of parents of a child with Down or Rett Syndrome. Morbidity of the syndromes and the marital status of the couples before and after the birth of the affected children were considered variables. The divorce rate in families with Down syndrome was 10%, similar to the Brazilian rate population. In Rett Syndrome, the divorce rate was significantly higher, 23.5%. The higher morbidity of Rett Syndrome, and the moment of diagnosis could be relevant factors for the increased divorce rate related to this syndrome.

Rett syndrome

PubMed Central

Sitholey, Prabhat; Agarwal, Vivek; Srivastava, Rohit

2005-01-01

Rett syndrome is a rare, progressive, neurodevelopmental disorder that has been reported only in the girl child. We describe the case of a 6.9-year-old girl with Rett syndrome. She had normal development till the age of 2 years. However, over the next 4–5 months, she lost her acquired, purposeful hand skills; expressive and receptive language; and reciprocal social interaction; and gradually developed a broad-based gait and typical midline stereotyped hand movements (mouthing, rubbing). PMID:20711295

Increased skewing of X chromosome inactivation in Rett syndrome patients and their mothers.

PubMed

Knudsen, Gun Peggy S; Neilson, Tracey C S; Pedersen, June; Kerr, Alison; Schwartz, Marianne; Hulten, Maj; Bailey, Mark E S; Orstavik, Karen Helene

2006-11-01

Rett syndrome is a largely sporadic, X-linked neurological disorder with a characteristic phenotype, but which exhibits substantial phenotypic variability. This variability has been partly attributed to an effect of X chromosome inactivation (XCI). There have been conflicting reports regarding incidence of skewed X inactivation in Rett syndrome. In rare familial cases of Rett syndrome, favourably skewed X inactivation has been found in phenotypically normal carrier mothers. We have investigated the X inactivation pattern in DNA from blood and buccal cells of sporadic Rett patients (n=96) and their mothers (n=84). The mean degree of skewing in blood was higher in patients (70.7%) than controls (64.9%). Unexpectedly, the mothers of these patients also had a higher mean degree of skewing in blood (70.8%) than controls. In accordance with these findings, the frequency of skewed (XCI > or =80%) X inactivation in blood was also higher in both patients (25%) and mothers (30%) than in controls (11%). To test whether the Rett patients with skewed X inactivation were daughters of skewed mothers, 49 mother-daughter pairs were analysed. Of 14 patients with skewed X inactivation, only three had a mother with skewed X inactivation. Among patients, mildly affected cases were shown to be more skewed than more severely affected cases, and there was a trend towards preferential inactivation of the paternally inherited X chromosome in skewed cases. These findings, particularly the greater degree of X inactivation skewing in Rett syndrome patients, are of potential significance in the analysis of genotype-phenotype correlations in Rett syndrome.

What Causes Rett Syndrome?

MedlinePlus

... early-onset seizure variant of Rett syndrome. Human Molecular Genetics , Jul 15;14(14), 1935–1946. Retrieved June ... Dragich, J., & Schanen, C. (2003). Rett Syndrome: Clinical-Molecular Correlates. In G. Fisch (Ed.), Genetics and neurobehavioral disorders (pp. 391–418). Totowa, NJ: ...

Spectrum of MECP2 gene mutations in a cohort of Indian patients with Rett syndrome: report of two novel mutations.

PubMed

Das, Dhanjit Kumar; Raha, Sarbani; Sanghavi, Daksha; Maitra, Anurupa; Udani, Vrajesh

2013-02-15

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, primarily affecting females and characterized by developmental regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. Rett syndrome is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene. Over 270 individual nucleotide changes which cause pathogenic mutations have been reported. However, eight most commonly occurring missense and nonsense mutations account for almost 70% of all patients. We screened 90 individuals with Rett syndrome phenotype. A total of 19 different MECP2 mutations and polymorphisms were identified in 27 patients. Of the 19 mutations, we identified 7 (37%) frameshift, 6 (31%) nonsense, 14 (74%) missense mutations and one duplication (5%). The most frequent pathogenic changes were: missense p.T158M (11%), p.R133C (7.4%), and p.R306C (7.4%) and nonsense p.R168X (11%), p.R255X (7.4%) mutations. We have identified two novel mutations namely p.385-388delPLPP present in atypical patients and p.Glu290AlafsX38 present in a classical patient of Rett syndrome. Sequence homology for p.385-388delPLPP mutation revealed that these 4 amino acids were conserved across mammalian species. This indicated the importance of these 4 amino acids in structure and function of the protein. A novel variant p.T479T has also been identified in a patient with atypical Rett syndrome. A total of 62 (69%) patients remained without molecular genetics diagnosis that necessitates further search for mutations in other genes like CDKL5 and FOXG1 that are known to cause Rett phenotype. The majority of mutations are detected in exon 4 and only one mutation was present in exon 3. Therefore, our study suggests the need for screening exon 4 of MECP2 as first line of diagnosis in these patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Rett'S syndrome : a case report.

PubMed

Gupta, V

2001-01-01

Rett's syndrome is a rare condition affecting only the girl child. It presents as a pervasive developmental disorder with a remarkable behavioural phenotype. The cause for this remains unknown but genetic factors and brain dysfunction have been implicated. This case report emphasises the importance of being aware of rare yet significant disorders of interest to neuro-developmental psychiatrists.

RETT'S SYNDROME : A CASE REPORT

PubMed Central

Gupta, Vinay

2001-01-01

Rett's syndrome is a rare condition affecting only the girl child. It presents as a pervasive developmental disorder with a remarkable behavioural phenotype. The cause for this remains unknown but genetic factors and brain dysfunction have been implicated. This case report emphasises the importance of being aware of rare yet significant disorders of interest to neuro-developmental psychiatrists. PMID:21407847

CDKL5 gene status in female patients with epilepsy and Rett-like features: two new mutations in the catalytic domain

PubMed Central

2012-01-01

Background Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) located in the Xp22 region have been shown to cause a subset of atypical Rett syndrome with infantile spasms or early seizures starting in the first postnatal months. Methods We performed mutation screening of CDKL5 in 60 female patients who had been identified as negative for the methyl CpG-binding protein 2 gene (MECP2) mutations, but who had current or past epilepsy, regardless of the age of onset, type, and severity. All the exons in the CDKL5 gene and their neighbouring sequences were examined, and CDKL5 rearrangements were studied by multiplex ligation-dependent probe amplification (MLPA). Results Six previously unidentified DNA changes were detected, two of which were disease-causing mutations in the catalytic domain: a frameshift mutation (c.509_510insGT; p.Glu170GlyfsX36) and a complete deletion of exon 10. Both were found in patients with seizures that started in the first month of life. Conclusions This study demonstrated the importance of CDKL5 mutations as etiological factors in neurodevelopmental disorders, and indicated that a thorough analysis of the CDKL5 gene sequence and its rearrangements should be considered in females with Rett syndrome-like phenotypes, severe encephalopathy and epilepsy with onset before 5 months of age. This study also confirmed the usefulness of MLPA as a diagnostic screening method for use in clinical practice. PMID:22867051

CDKL5 gene status in female patients with epilepsy and Rett-like features: two new mutations in the catalytic domain.

PubMed

Maortua, Hiart; Martínez-Bouzas, Cristina; Calvo, María-Teresa; Domingo, Maria-Rosario; Ramos, Feliciano; García-Ribes, Ainhoa; Martínez, María-Jesús; López-Aríztegui, María-Asunción; Puente, Nerea; Rubio, Izaskun; Tejada, María-Isabel

2012-08-06

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) located in the Xp22 region have been shown to cause a subset of atypical Rett syndrome with infantile spasms or early seizures starting in the first postnatal months. We performed mutation screening of CDKL5 in 60 female patients who had been identified as negative for the methyl CpG-binding protein 2 gene (MECP2) mutations, but who had current or past epilepsy, regardless of the age of onset, type, and severity. All the exons in the CDKL5 gene and their neighbouring sequences were examined, and CDKL5 rearrangements were studied by multiplex ligation-dependent probe amplification (MLPA). Six previously unidentified DNA changes were detected, two of which were disease-causing mutations in the catalytic domain: a frameshift mutation (c.509_510insGT; p.Glu170GlyfsX36) and a complete deletion of exon 10. Both were found in patients with seizures that started in the first month of life. This study demonstrated the importance of CDKL5 mutations as etiological factors in neurodevelopmental disorders, and indicated that a thorough analysis of the CDKL5 gene sequence and its rearrangements should be considered in females with Rett syndrome-like phenotypes, severe encephalopathy and epilepsy with onset before 5 months of age. This study also confirmed the usefulness of MLPA as a diagnostic screening method for use in clinical practice.

A perspective on "cure" for Rett syndrome.

PubMed

Clarke, Angus John; Abdala Sheikh, Ana Paula

2018-04-02

The reversal of the Rett syndrome disease process in the Mecp2 mouse model of Guy et al. (2007) has motivated families and researchers to work on this condition. The reversibility in adult mice suggests that there is potentially much to be gained from rational treatments applied to patients of any age. However, it may be difficult to strike the right balance between enthusiasm on the one hand and realism on the other. One effect of this has been a fragmentation of the "Rett syndrome community" with some groups giving priority to work aimed at a cure while fewer resources are devoted to medical or therapy-based interventions to enhance the quality of life of affected patients or provide support for their families.Several possible therapeutic approaches are under development that, it is claimed and hoped, may lead to a "cure" for patients with Rett syndrome. While all have a rationale, there are potential obstacles to each being both safe and effective. Furthermore, any strategy that succeeded in restoring normal levels of MECP2 gene expression throughout the brain carries potential pitfalls, so that it will be of crucial importance to introduce any clinical trials of such therapies with great care.Expectations of families for a radical, rational treatment should not be inflated beyond a cautious optimism. This is particularly because affected patients with us now may not be able to reap the full benefits of a "cure". Thus, interventions aimed at enhancing the quality of life of affected patients should not be forgone and their importance should not be minimised.

Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity.

PubMed

Kondo, Mari A; Gray, Laura J; Pelka, Gregory J; Leang, Sook-Kwan; Christodoulou, John; Tam, Patrick P L; Hannan, Anthony J

2016-02-01

Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from a range of debilitating physical symptoms, however, behavioral and emotional symptoms also severely affect their quality of life. Here, we present previously unreported and clinically relevant affective dysfunction in the female heterozygous Mecp2(tm1Tam) mouse model of RTT (129sv and C57BL6 mixed background). The affective dysfunction and aberrant anxiety-related behavior of the Mecp2(+/-) mice were found to be reversible with environmental enrichment (EE) from 4 weeks of age. The effect of exercise alone (via wheel running) was also explored, providing the first evidence that increased voluntary physical activity in an animal model of RTT is beneficial for some phenotypes. Mecp2(+/-) mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating hypothalamic-pituitary-adrenal axis dysregulation. EE of Mecp2(+/-) mice normalized basal serum corticosterone and hippocampal BDNF protein levels. The enrichment-induced rescue appears independent of the transcriptional regulation of the MeCP2 targets Bdnf exon 4 and Crh. These findings provide new insight into the neurodevelopmental role of MeCP2 and pathogenesis of RTT, in particular the affective dysfunction. The positive outcomes of environmental stimulation and physical exercise have implications for the development of therapies targeting the affective symptoms, as well as behavioral and cognitive dimensions, of this devastating neurodevelopmental disorder. © 2015 Wiley Periodicals, Inc.

Brief Report: Systematic Review of Rett Syndrome in Males

ERIC Educational Resources Information Center

Reichow, Brian; George-Puskar, Annie; Lutz, Tara; Smith, Isaac C.; Volkmar, Fred R.

2015-01-01

Rett syndrome (RTT) is a neurogenetic disorder in which a period of typical development is followed by loss of previously acquired skills. Once thought to occur exclusively in females, increasing numbers of male cases of RTT have been reported. This systematic review included 36 articles describing 57 cases of RTT in males. Mutations of the MECP2…

Parental perspectives on the communication abilities of their daughters with Rett syndrome.

PubMed

Urbanowicz, Anna; Leonard, Helen; Girdler, Sonya; Ciccone, Natalie; Downs, Jenny

2016-01-01

This study describes, from the perspective of parents, how females with Rett syndrome communicate in everyday life and the barriers and facilitators to successful communication. Sixteen interviews were conducted with parents with a daughter with Rett syndrome with a pathogenic mutation in the methyl-CpG-binding protein 2 gene. Interviews were recorded and transcribed verbatim. Transcripts were analysed using directed content analysis. All parents reported their daughters were able to express discomfort and pleasure, and make requests and choices using a variety of modalities including vocalisations, body movements and eye gaze. Parents also reported their daughters understood most of what they said and that the level of functional abilities, such as mobility, and environmental factors, such as characteristics of the communication partner, influenced successful communication. The perspectives of parents are integral to the assessment of communication abilities and have the potential to inform communication interventions for girls and women with Rett syndrome.

Direct Observation of the Behaviour of Females with Rett Syndrome.

PubMed

Cianfaglione, Rina; Meek, Andrea; Clarke, Angus; Kerr, Michael; Hastings, Richard P; Felce, David

The aim was to observe the behaviour of a sample of females with RTT and explore how it was organized in relation to environmental events. Ten participants, all with a less severe form of classic ( n  = 9) or atypical ( n  = 1) Rett syndrome (RTT), were filmed at home and at school or day centre. Analysis used real-time data capture software. Observational categories distinguished engagement in social and non-social pursuits, hand stereotypies, self-injury and the receipt of attention from a parent, teacher or carer. Associations between participant behaviour and intake variables and receipt of attention were explored. Concurrent and lagged conditional probabilities between behavioural categories and receipt of attention were calculated. Receipt of adult attention was high. Engagement in activity using the hands was associated with a less severe condition and greater developmental age. Engagement in activity, whether using the hands or not, and social engagement were positively associated with receipt of support. The extent of hand stereotypies varied greatly across participants but was independent of environmental events. Six participants self-injured. There was some evidence that self-injury was related to adult attention. Participants appeared to experience a carer and attention rich environment and their levels of engagement seemed high as a result. As in the more general literature, engagement in activity was related to personal development and to social support. Self-injury contrasted with hand stereotypies in having possible environmental function.

Self-Injurious Behavior in Rett Syndrome: Interactions between Features of Rett Syndrome and Operant Conditioning.

ERIC Educational Resources Information Center

Oliver, Chris; And Others

1993-01-01

In this case study, interactions were examined between features of Rett syndrome and operant conditioning as determinants of self-injurious behavior (SIB). Analysis suggested different functions for two forms of SIB: automatic reinforcement by sensory stimulation and escape from social interactions. Features of Rett syndrome tended to maximize the…

Validating the Rett Syndrome Gross Motor Scale.

PubMed

Downs, Jenny; Stahlhut, Michelle; Wong, Kingsley; Syhler, Birgit; Bisgaard, Anne-Marie; Jacoby, Peter; Leonard, Helen

2016-01-01

Rett syndrome is a pervasive neurodevelopmental disorder associated with a pathogenic mutation on the MECP2 gene. Impaired movement is a fundamental component and the Rett Syndrome Gross Motor Scale was developed to measure gross motor abilities in this population. The current study investigated the validity and reliability of the Rett Syndrome Gross Motor Scale. Video data showing gross motor abilities supplemented with parent report data was collected for 255 girls and women registered with the Australian Rett Syndrome Database, and the factor structure and relationships between motor scores, age and genotype were investigated. Clinical assessment scores for 38 girls and women with Rett syndrome who attended the Danish Center for Rett Syndrome were used to assess consistency of measurement. Principal components analysis enabled the calculation of three factor scores: Sitting, Standing and Walking, and Challenge. Motor scores were poorer with increasing age and those with the p.Arg133Cys, p.Arg294* or p.Arg306Cys mutation achieved higher scores than those with a large deletion. The repeatability of clinical assessment was excellent (intraclass correlation coefficient for total score 0.99, 95% CI 0.93-0.98). The standard error of measurement for the total score was 2 points and we would be 95% confident that a change 4 points in the 45-point scale would be greater than within-subject measurement error. The Rett Syndrome Gross Motor Scale could be an appropriate measure of gross motor skills in clinical practice and clinical trials.

Speech and motor disturbances in Rett syndrome.

PubMed

Bashina, V M; Simashkova, N V; Grachev, V V; Gorbachevskaya, N L

2002-01-01

Rett syndrome is a severe, genetically determined disease of early childhood which produces a defined clinical phenotype in girls. The main clinical manifestations include lesions affecting speech functions, involving both expressive and receptive speech, as well as motor functions, producing apraxia of the arms and profound abnormalities of gait in the form of ataxia-apraxia. Most investigators note that patients have variability in the severity of derangement to large motor acts and in the damage to fine hand movements and speech functions. The aims of the present work were to study disturbances of speech and motor functions over 2-5 years in 50 girls aged 12 months to 14 years with Rett syndrome and to analyze the correlations between these disturbances. The results of comparing clinical data and EEG traces supported the stepwise involvement of frontal and parietal-temporal cortical structures in the pathological process. The ability to organize speech and motor activity is affected first, with subsequent development of lesions to gnostic functions, which are in turn followed by derangement of subcortical structures and the cerebellum and later by damage to structures in the spinal cord. A clear correlation was found between the severity of lesions to motor and speech functions and neurophysiological data: the higher the level of preservation of elements of speech and motor functions, the smaller were the contributions of theta activity and the greater the contributions of alpha and beta activities to the EEG. The possible pathogenetic mechanisms underlying the motor and speech disturbances in Rett syndrome are discussed.

Investigating genotype-phenotype relationships in Rett syndrome using an international data set.

PubMed

Bebbington, A; Anderson, A; Ravine, D; Fyfe, S; Pineda, M; de Klerk, N; Ben-Zeev, B; Yatawara, N; Percy, A; Kaufmann, W E; Leonard, H

2008-03-11

Rett syndrome is an uncommon neurodevelopmental disorder with an incidence of 1:9,000 live female births. The principal genetic cause was first reported in 1999 when the association with mutations in the methyl-CpG-binding protein 2 (or MECP2) gene was identified. This study uses data from a large international database, InterRett, to examine genotype-phenotype relationships and compares these with previous findings in a population-based cohort. The data set for these analyses was derived from a subset of InterRett cases with subject information collected from the family, the clinician, or both. Individual phenotypic characteristics and clinical severity using three scales were compared among those with eight known recurrent pathogenic MECP2 mutations as well as those with C-terminal deletions (n = 272). Overall, p.R270X and p.R255X were the most severe and p.R133C and p.R294X were the mildest mutations. Significant differences by mutation were seen for individual phenotypic characteristics such as hand use, ambulation, and language. This multicenter investigation into the phenotypic correlates of MECP2 mutations in Rett syndrome has provided a greater depth of understanding than hitherto available about the specific phenotypic characteristics associated with commonly occurring mutations. Although the modifying influence of X inactivation on clinical severity could not be included in the analysis, the findings confirm clear genotype-phenotype relationships in Rett syndrome and show the benefits of collaboration crucial to effective research in rare disorders.

Brain perfusion abnormalities in Rett syndrome: a qualitative and quantitative SPET study with 99Tc(m)-ECD.

PubMed

Burroni, L; Aucone, A M; Volterrani, D; Hayek, Y; Bertelli, P; Vella, A; Zappella, M; Vattimo, A

1997-06-01

Rett syndrome is a progressive neurological paediatric disorder associated with severe mental deficiency, which affects only girls. The aim of this study was to determine if brain blood flow abnormalities detected with 99Tc(m)-ethyl-cysteinate-dimer (99Tc[m]-ECD) single photon emission tomography (SPET) can explain the clinical manifestation and progression of the disease. Qualitative and quantitative global and regional brain blood flow was evaluated in 12 girls with Rett syndrome and compared with an aged-matched reference group of children. In comparison with the reference group, SPET revealed a considerable global reduction in cerebral perfusion in the groups of girls with Rett syndrome. A large statistical difference was noted, which was more evident when comparing the control group with girls with stage IV Rett syndrome than girls with stage III Rett syndrome. The reduction in cerebral perfusion reflects functional disturbance in the brain of children with Rett syndrome. These data confirm that 99Tc(m)-ECD brain SPET is sensitive in detecting hypoperfused areas in girls with Rett syndrome that may be associated with brain atrophy, even when magnetic resonance imaging appears normal.

Rett Syndrome: Of Girls and Mice--Lessons for Regression in Autism

ERIC Educational Resources Information Center

Glaze, Daniel G.

2004-01-01

Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females. Regression is a defining feature of RTT. During the regression stage, RTT girls display many autistic features, such as loss of communication and social skills, poor eye contact, and lack of interest, and initially may be given the diagnosis of autism.…

FOXG1 Is Responsible for the Congenital Variant of Rett Syndrome

PubMed Central

Ariani, Francesca; Hayek, Giuseppe; Rondinella, Dalila; Artuso, Rosangela; Mencarelli, Maria Antonietta; Spanhol-Rosseto, Ariele; Pollazzon, Marzia; Buoni, Sabrina; Spiga, Ottavia; Ricciardi, Sara; Meloni, Ilaria; Longo, Ilaria; Mari, Francesca; Broccoli, Vania; Zappella, Michele; Renieri, Alessandra

2008-01-01

Rett syndrome is a severe neurodevelopmental disease caused by mutations in the X-linked gene encoding for the methyl-CpG-binding protein MeCP2. Here, we report the identification of FOXG1-truncating mutations in two patients affected by the congenital variant of Rett syndrome. FOXG1 encodes a brain-specific transcriptional repressor that is essential for early development of the telencephalon. Molecular analysis revealed that Foxg1 might also share common molecular mechanisms with MeCP2 during neuronal development, exhibiting partially overlapping expression domain in postnatal cortex and neuronal subnuclear localization. PMID:18571142

A rare male patient with classic Rett syndrome caused by MeCP2_e1 mutation.

PubMed

Tokaji, Narumi; Ito, Hiromichi; Kohmoto, Tomohiro; Naruto, Takuya; Takahashi, Rizu; Goji, Aya; Mori, Tatsuo; Toda, Yoshihiro; Saito, Masako; Tange, Shoichiro; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

2018-03-01

Rett syndrome (RTT) is a severe neurodevelopmental disorder typically affecting females. It is mainly caused by loss-of-function mutations that affect the coding sequence of exon 3 or 4 of methyl-CpG-binding protein 2 (MECP2). Severe neonatal encephalopathy resulting in death before the age of 2 years is the most common phenotype observed in males affected by a pathogenic MECP2 variant. Mutations in MECP2 exon 1 affecting the MeCP2_e1 isoform are relatively rare causes of RTT in females, and only one case of a male patient with MECP2-related severe neonatal encephalopathy caused by a mutation in MECP2 exon 1 has been reported. This is the first reported case of a male with classic RTT caused by a 5-bp duplication in the open-reading frame of MECP2 exon 1 (NM_001110792.1:c.23_27dup) that introduced a premature stop codon [p.(Ser10Argfs*36)] in the MeCP2_e1 isoform, which has been reported in one female patient with classic RTT. Therefore, both males and females displaying at least some type of MeCP2_e1 mutation may exhibit the classic RTT phenotype. © 2018 Wiley Periodicals, Inc.

Rett Syndrome Turns 50: Themes From a Chronicle: Medical Perspectives and the Human Face of Rett Syndrome.

PubMed

Ronen, Gabriel M; Rosenbaum, Peter L

2016-08-01

Fifty years ago Andreas Rett first described in great detail what came to be known as "Rett syndrome." Understanding girls and women with this syndrome and their families helped in many ways to revolutionize modern neurodevelopmental medicine. For some people the identification of the genetic underpinning of the syndrome and the ongoing biological research into this condition represented the peak of the scientific accomplishments in Rett syndrome. For others, it was developments in clinical research methodologies that were especially important. Above all, the patient- and family-oriented empathetic and collaborative approach to care by professionals collaborating with families has led to immense achievements, both scientific and humanistic. The aim of this narrative was to describe the medical and personal life story of a young woman with Rett syndrome and to offer a history that highlights developments in the unraveling of this condition from its initial recognition to our current understanding. We believe that much can be learned from the humanistic style of care provision combined with the best possible level of assisted autonomy and life enjoyment of the young woman with Rett syndrome. In addition, the approach to collaborative research by dedicated and often charitable leaders in the field can teach us many important lessons about the ethics of clinical and health services research. Copyright © 2016 Elsevier Inc. All rights reserved.

Epidemiology of Rett syndrome in Serbia: prevalence, incidence and survival.

PubMed

Sarajlija, Adrijan; Kisic-Tepavcevic, Darija; Nikolic, Zorana; Savic Pavicevic, Dusanka; Obradovic, Slobodan; Djuric, Milena; Pekmezovic, Tatjana

2015-01-01

Rett syndrome (RTT) is a severe neurodevelopmental disorder that represents the second most common cause of mental retardation in females. However, incidence and prevalence of RTT are scarcely reported. A retrospective study included all patients with RTT diagnosed between 1981 and 2012 in Serbia. Estimation of incidence and prevalence was calculated on the basis of vital statistics reported by Statistical Office of Republic of Serbia. From 1981 to 2012, RTT has been diagnosed in 102 girls in Serbia. Incidence of RTT in Serbia is estimated at 0.586:10,000 female live births. We estimated the prevalence of RTT in population of females younger than 19 years at 1:8,439. Death occurred in 19 patients (18.63%), with pneumonia as the most common cause. The lethal outcome by the age of 12 years could be expected for 11% of patients. The mean age at diagnosis was 3.5 years and we have confirmed a significant trend towards earlier dianosis during studied period. Rett syndrome incidence in Serbia is in accordance with reports from other countries. Serbian RTT patients have increased risk for early death when compared to patients in more developed countries, most commonly due to pneumonia. There was significant trend towards early diagnosis of RTT in Serbia over recent decades. © 2015 S. Karger AG, Basel.

A Mutation in the Rett Syndrome Gene, MECP2, Causes X-Linked Mental Retardation and Progressive Spasticity in Males

PubMed Central

Meloni, Ilaria; Bruttini, Mirella; Longo, Ilaria; Mari, Francesca; Rizzolio, Flavio; D’Adamo, Patrizia; Denvriendt, Koenraad; Fryns, Jean-Pierre; Toniolo, Daniela; Renieri, Alessandra

2000-01-01

Heterozygous mutations in the X-linked MECP2 gene cause Rett syndrome, a severe neurodevelopmental disorder of young females. Only one male presenting an MECP2 mutation has been reported; he survived only to age 1 year, suggesting that mutations in MECP2 are male lethal. Here we report a three-generation family in which two affected males showed severe mental retardation and progressive spasticity, previously mapped in Xq27.2-qter. Two obligate carrier females showed either normal or borderline intelligence, simulating an X-linked recessive trait. The two males and the two obligate carrier females presented a mutation in the MECP2 gene, demonstrating that, in males, MECP2 can be responsible for severe mental retardation associated with neurological disorders. PMID:10986043

Autistic Disorder Symptoms in Rett Syndrome

ERIC Educational Resources Information Center

Wulffaert, Josette; Van Berckelaer-Onnes, Ina A.; Scholte, Evert M.

2009-01-01

According to the major classification systems it is not possible to diagnose a comorbid autistic disorder in persons with Rett syndrome. However, this is a controversial issue, and given the level of functioning of persons with Rett syndrome, the autistic disorder is expected to be present in a comparable proportion as in people with the same…

Rett Syndrome

MedlinePlus

... with movement and coordination, and a loss of social interaction and communication. Stage III: plateau. The third stage usually begins between the ages of 2 and 10 years and can last for many years. ... social functioning Shortened life span — people with Rett syndrome ...

Improving Functional Skills and Physical Fitness in Children with Rett Syndrome

ERIC Educational Resources Information Center

Lotan, M.; Isakov, E.; Merrick, J.

2004-01-01

To investigate the feasibility of a physical exercise programme with treadmill for persons with Rett syndrome (RS) in order to promote fitness and health. A daily training programme on a treadmill was designed for four females with RS over a period of 2 months with tests performed in three intervals, at time 1, 2 and 3, 2 months apart with…

Longitudinal course of epilepsy in Rett syndrome and related disorders

PubMed Central

Tarquinio, Daniel C; Hou, Wei; Berg, Anne; Kaufmann, Walter E; Lane, Jane B; Skinner, Steven A; Motil, Kathleen J; Neul, Jeffrey L; Percy, Alan K; Glaze, Daniel G

2017-01-01

Abstract Epilepsy is common in Rett syndrome, an X-linked dominant disorder caused by mutations in the MECP2 gene, and in Rett-related disorders, such as MECP2 duplication. However, neither the longitudinal course of epilepsy nor the patterns of seizure onset and remission have been described in Rett syndrome and related conditions. The present study summarizes the findings of the Rett syndrome Natural History study. Participants with clinical Rett syndrome and those with MECP2 mutations without the clinical syndrome were recruited through the Rett Natural History study from 2006 to 2015. Clinical details were collected, and cumulative lifetime prevalence of epilepsy was determined using the Kaplan-Meier estimator. Risk factors for epilepsy were assessed using Cox proportional hazards models. Of 1205 participants enrolled in the study, 922 had classic Rett syndrome, and 778 of these were followed longitudinally for 3939 person-years. The diagnosis of atypical Rett syndrome with a severe clinical phenotype was associated with higher prevalence of epilepsy than those with classic Rett syndrome. While point prevalence of active seizures ranged from 30% to 44%, the estimated cumulative lifetime prevalence of epilepsy using Kaplan-Meier approached 90%. Specific MECP2 mutations were not significantly associated with either seizure prevalence or seizure severity. In contrast, many clinical features were associated with seizure prevalence; frequency of hospitalizations, inability to walk, bradykinesia, scoliosis, gastrostomy feeding, age of seizure onset, and late age of diagnosis were independently associated with higher odds of an individual having epilepsy. Aggressive behaviour was associated with lower odds. Three distinct patterns of seizure prevalence emerged in classic Rett syndrome, including those who did not have seizures throughout the study, those who had frequent relapse and remission, and those who had relentless seizures. Although 248 of those with classic

IgA Antibodies in Rett Syndrome

ERIC Educational Resources Information Center

Reichelt, K. L.; Skjeldal, O.

2006-01-01

The level of IgA antibodies to gluten and gliadin proteins found in grains and to casein found in milk, as well as the level of IgG to gluten and gliadin, have been examined in 23 girls with Rett syndrome and 53 controls. Highly statistically significant increases were found for the Rett population compared to the controls. The reason for this…

Rett syndrome: stimulation of endogenous biogenic amines.

PubMed

Pelligra, R; Norton, R D; Wilkinson, R; Leon, H A; Matson, W R

1992-06-01

Transient hypercapnic hyperoxemia was induced in two Rett syndrome children by the administration of a gaseous mixture of 80% O2 and 20% CO2. Time course studies of neurotransmitters and their metabolites showed an immediate and marked increase in central biogenic amine turnover following inhalation of the gas mixture. The increased turnover of biogenic amines was associated with improved clinical changes. This suggests a coupled relationship and provides further support for an etiological role of neurotransmitter dysfunction in Rett syndrome. In a complementary study, elevation of pulmonary CO2 by application of a simple rebreathing device resulted in improvement of abnormal blood gases and elimination of the Cheyne-Stokes-like respiratory pattern of the Rett syndrome. Near normalization of the EEG occurred when a normal respiratory pattern was imposed by means of a respirator. Taken together, these results lead to the preliminary conclusion that cerebral hypoxemia secondary to abnormal respiratory function may contribute to diminished production of biogenic amines in Rett syndrome.

Rett syndrome - Stimulation of endogenous biogenic amines

NASA Technical Reports Server (NTRS)

Pelligra, R.; Norton, R. D.; Wilkinson, R.; Leon, H. A.; Matson, W. R.

1992-01-01

Transient hypercapnic hyperoxemia was induced in two Rett syndrome children by the administration of a gaseous mixture of 80 percent O2 and 20 percent CO2. Time course studies of neurotransmitters and their metabolites showed an immediate and marked increase in central biogenic amine turnover following inhalation of the gas mixture. The increased turnover of biogenic amines was associated with improved clinical changes. This suggests a coupled relationship and provides further support for an etiological role of neurotransmitter dysfunction in Rett syndrome. In a complementary study, elevation of pulmonary CO2 by application of a simple rebreathing device resulted in improvement of abnormal blood gases and elimination of the Cheyne-Stokes-like respiratory pattern of the Rett syndrome. Near normalization of the EEG occurred when a normal respiratory pattern was imposed by means of a respirator. Taken together, these results lead to the preliminary conclusion that cerebral hypoxemia secondary to abnormal respiratory function may contribute to diminished production of biogenic amines in Rett syndrome.

MECP2 gene study in a large cohort: testing of 240 female patients and 861 healthy controls (519 females and 342 males).

PubMed

Maortua, Hiart; Martínez-Bouzas, Cristina; García-Ribes, Ainhoa; Martínez, María-Jesus; Guillen, Encarna; Domingo, María-Rosario; Calvo, María-Teresa; Guitart, Miriam; Gabau, Elisabeth; Botella, María-Pilar; Gener, Blanca; Rubio, Izaskun; López-Aríztegui, María-Asunción; Tejada, María-Isabel

2013-09-01

The MECP2 gene located on Xq28 is one of the most important genes contributing to the spectrum of neurodevelopmental disorders. Therefore, we present our experience in the molecular study of this gene. MECP2 was thoroughly tested for the presence of mutations (sequencing of four exons and rearrangements) in 120 female patients: 28 with classic Rett syndrome, five with atypical Rett syndrome, and 87 with heterogeneous phenotypes with some Rett-like features. Another 120 female patients with intellectual disability of unknown origin were also studied, but in these cases we only tested exons 3 and 4. Finally, 861 healthy controls (519 females and 342 males) were also studied for exon 3 and 4. Eighteen different pathological mutations were found, five of them previously undescribed, and four large deletions detected by multiplex ligation-dependent probe amplification. All were de novo mutations not present in the parents. In conclusion, i) MECP2 is one of the most important genes in the diagnosis of genetic intellectual disability in females; ii) MECP2 must be studied not only in patients with classical/atypical Rett syndrome but also in patients with other phenotypes related to Rett syndrome; and iii) for the new variants, it is important to perform complementary studies, including the analysis of large populations of healthy individuals and the use of in silico programs. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Determinants of sleep disturbances in Rett syndrome: Novel findings in relation to genotype.

PubMed

Boban, Sharolin; Wong, Kingsley; Epstein, Amy; Anderson, Barbara; Murphy, Nada; Downs, Jenny; Leonard, Helen

2016-09-01

Rett syndrome is a rare but severe neurological disorder associated with a mutation in the methyl CpG binding protein 2 (MECP2) gene. Sleep problems and epilepsy are two of many comorbidities associated with this disorder. This study investigated the prevalence and determinants of sleep problems in Rett syndrome using an international sample. Families with a child with a confirmed Rett syndrome diagnosis and a MECP2 mutation registered in the International Rett Syndrome Phenotype Database (InterRett) were invited to participate. Questionnaires were returned by 364/461 (78.9%) either in web-based or paper format. Families completed the Sleep Disturbance Scale for Children and provided information on the presence, nature, and frequency of their child's sleep problems. Multivariate multinomial regression was used to investigate the relationships between selected sleep problems, age group, and genotype and linear regression for the relationships between sleep disturbance scales and a range of covariates. Night waking was the most prevalent sleep problem affecting over 80% with nearly half (48.3%) currently waking often at night. Initiating and maintaining sleep was most disturbed for younger children and those with a p.Arg294* mutation. Severe seizure activity was associated with poor sleep after adjusting for age group, mutation type, and mobility. We were surprised to find associations between the p.Arg294* mutation and some sleep disturbances given that other aspects of its phenotype are milder. These findings highlight the complexities of aberrant MECP2 function in Rett syndrome and explain some of the variation in manifestation of sleep disturbances. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Rett Syndrome.

ERIC Educational Resources Information Center

Culbert, Linda A.

This pamphlet reviews the historical process involved in initially recognizing Rett Syndrome as a specific disorder in girls. Its etiology is unknown, but studies have considered factors as hyperammonemia, a two-step mutation, a fragile X chromosome, metabolic disorder, environmental causation, dopamine deficiency, and an inactive X chromosome.…

Oral findings in Rett syndrome: a systematic review of the dental literature.

PubMed

Fuertes-González, María-Cristina; Silvestre, Francisco-Javier; Almerich-Silla, José-Manuel

2011-01-01

Rett syndrome (RS) is a chromosome X-linked genetic neurological disorder characterized by developmental regression, particularly in relation to expressive language and use of the hands, together with profound mental retardation, that almost exclusively affects females. The present review describes the 35 cases of RS published in the indexed literature (Medline)--the first corresponding to 1985 and the last to the year 2007. Certain oral manifestations of the disease are derived from the drug treatment prescribed to control the disease, while others are common to other clinical conditions characterized by convulsion activity, difficulties for correct oral hygiene, walking problems and/or an excess of oral/digital-manual habits. In any case, bruxism is the oral habit most frequently associated with RS--the treatment of which remains the subject of controversy.

Pathogenesis of Lethal Cardiac Arrhythmias in Mecp2 Mutant Mice: Implication for Therapy in Rett Syndrome

PubMed Central

McCauley, Mark D.; Wang, Tiannan; Mike, Elise; Herrera, Jose; Beavers, David L.; Huang, Teng-Wei; Ward, Christopher S.; Skinner, Steven; Percy, Alan K.; Glaze, Daniel G.; Wehrens, Xander H. T.; Neul, Jeffrey L.

2013-01-01

Rett Syndrome is a neurodevelopmental disorder typically caused by mutations in Methyl-CpG-Binding Protein 2 (MECP2) in which 26% of deaths are sudden and of unknown cause. To explore the hypothesis that these deaths may be due to cardiac dysfunction, we characterized the electrocardiograms (ECGs) in 379 people with Rett syndrome and found that 18.5% show prolongation of the corrected QT interval (QTc), indicating a repolarization abnormality that can predispose to the development of an unstable fatal cardiac rhythm. Male mice lacking MeCP2 function, Mecp2Null/Y, also have prolonged QTc and show increased susceptibility to induced ventricular tachycardia. Female heterozygous null mice, Mecp2Null/+, show an age-dependent prolongation of QTc associated with ventricular tachycardia and cardiac-related death. Genetic deletion of MeCP2 function in only the nervous system was sufficient to cause long QTc and ventricular tachycardia, implicating neuronally-mediated changes to cardiac electrical conduction as a potential cause of ventricular tachycardia in Rett syndrome. The standard therapy for prolonged QTc in Rett syndrome, β-adrenergic receptor blockers, did not prevent ventricular tachycardia in Mecp2Null/Y mice. To determine whether an alternative therapy would be more appropriate, we characterized cardiomyocytes from Mecp2Null/Y mice and found increased persistent sodium current, which was normalized when cells were treated with the sodium channel-blocking anti-seizure drug phenytoin. Treatment with phenytoin reduced both QTc and sustained ventricular tachycardia in Mecp2Null/Y mice. These results demonstrate that cardiac abnormalities in Rett syndrome are secondary to abnormal nervous system control, which leads to increased persistent sodium current. Our findings suggest that treatment in people with Rett syndrome would be more effective if it targeted the increased persistent sodium current in order to prevent lethal cardiac arrhythmias. PMID:22174313

What are patients with Rett syndrome interested in?

PubMed

Hirano, Daisuke; Taniguchi, Takamichi

2018-02-01

[Purpose] Rett syndrome is a severe neurodevelopmental disease; individuals typically have no verbal skills or purposeful hand movements. In clinical settings, knowledge of their interests would be helpful for therapy. Therefore, we investigated the interests of Rett syndrome patients. [Subjects and Methods] In 2016, we sent a questionnaire regarding the interests of individuals with Rett syndrome to 1,016 directors of schools for special needs education and 204 directors of rehabilitation departments (130 facilities for persons with severe motor and intellectual disabilities, 73 wards for patients with severe motor and intellectual disabilities, and the National Hospital Organization and National Center Hospital, and the National Center of Neurology and Psychiatry) in Japan. We used descriptive statistics and content analysis to examine the answers to the questionnaires. [Results] Information was acquired from 216 individuals (3-53 years old) with Rett syndrome. 92.9% of the individuals were reported to have some interests (e.g., in people, music, things to see, animation, or books). [Conclusion] Individuals with Rett syndrome were observed to be interested in various things despite their having severe motor and intellectual disabilities. These findings suggest that family members and care staff might facilitate various changes or developments of these individuals and discover their hidden strengths by focusing on their interests.

Longitudinal brain MRI study in a mouse model of Rett Syndrome and the effects of choline.

PubMed

Ward, B C; Agarwal, S; Wang, K; Berger-Sweeney, J; Kolodny, N H

2008-07-01

Rett Syndrome (RTT), the second most common cause of mental retardation in girls, is associated with mutations of an X-linked gene encoding the transcriptional repressor protein MeCP2. Mecp2(1lox) mutant mice express no functional MeCP2 protein and exhibit behavioral abnormalities similar to those seen in RTT patients. Here we monitor the development of both whole brain and regional volumes between 21 and 42 days of age in this model of RTT using MRI. We see decreases in whole brain volumes in both male and female mutant mice. Cerebellar and ventricular volumes are also decreased in RTT males. Previous work has suggested that perinatal choline supplementation alleviates some of the behavioral deficits in both male and female Mecp2(1lox) mutant mice. Here we show that perinatal choline supplementation also positively affects whole brain volume in heterozygous females, and cerebellar volume in male RTT mice.

Randomized open-label trial of dextromethorphan in Rett syndrome.

PubMed

Smith-Hicks, Constance L; Gupta, Siddharth; Ewen, Joshua B; Hong, Manisha; Kratz, Lisa; Kelley, Richard; Tierney, Elaine; Vaurio, Rebecca; Bibat, Genila; Sanyal, Abanti; Yenokyan, Gayane; Brereton, Nga; Johnston, Michael V; Naidu, Sakkubai

2017-10-17

To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity. Dextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale. Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect. © 2017 American Academy of Neurology.

InterRett, a Model for International Data Collection in a Rare Genetic Disorder

ERIC Educational Resources Information Center

Louise, Sandra; Fyfe, Sue; Bebbington, Ami; Bahi-Buisson, Nadia; Anderson, Alison; Pineda, Merce; Percy, Alan; Zeev, Bruria Ben; Wu, Xi Ru; Bao, Xinhua; MacLeod, Patrick; Armstrong, Judith; Leonard, Helen

2009-01-01

Rett syndrome (RTT) is a rare genetic disorder within the autistic spectrum. This study compared socio-demographic, clinical and genetic characteristics of the international database, InterRett, and the population-based Australian Rett syndrome database (ARSD). It also explored the strengths and limitations of InterRett in comparison with other…

Variant of Rett syndrome and CDKL5 gene: clinical and autonomic description of 10 cases.

PubMed

Pini, Giorgio; Bigoni, Stefania; Engerström, Ingegerd Witt; Calabrese, Olga; Felloni, Beatrice; Scusa, Maria Flora; Di Marco, Pietro; Borelli, Paolo; Bonuccelli, Ubaldo; Julu, Peter O O; Nielsen, Jytte Bieber; Morin, Bodil; Hansen, Stig; Gobbi, Giuseppe; Visconti, Paola; Pintaudi, Maria; Edvige, Veneselli; Romanelli, Anna; Bianchi, Fabrizio; Casarano, Manuela; Battini, Roberta; Cioni, Giovanni; Ariani, Francesca; Renieri, Alessandra; Benincasa, Alberto; Delamont, Robert S; Zappella, Michele

2012-02-01

Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. In recent years more than 60 patients with mutations in the CDKL5 gene have been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all subjects an evaluation of the autonomic system was performed using the Neuroscope. Common features were gaze avoidance, repetitive head movements and hand stereotypies. The autonomic evaluation disclosed eight cases with the Forceful breather cardiorespiratory phenotype and two cases with the Apneustic breather phenotype. The clinical picture remains within the RTT spectrum but some symptoms are more pronounced in addition to the very early onset of seizures. The cardiorespiratory phenotype was dominated by Forceful breathers, while Feeble breathers were not found, differently from the general Rett population, suggesting a specific behavioral and cardiorespiratory phenotype of the RTT the Hanefeld variant. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Novel mutations in cyclin-dependent kinase-like 5 (CDKL5) gene in Indian cases of Rett syndrome.

PubMed

Das, Dhanjit Kumar; Mehta, Bhakti; Menon, Shyla R; Raha, Sarbani; Udani, Vrajesh

2013-03-01

Rett syndrome is a severe neurodevelopmental disorder, almost exclusively affecting females and characterized by a wide spectrum of clinical manifestations. Both the classic and atypical forms of Rett syndrome are primarily due to mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in patients with atypical Rett syndrome, X-linked infantile spasms sharing common features of generally early-onset seizures and mental retardation. CDKL5 is known as serine/threonine protein kinase 9 (STK9) and is mapped to the Xp22 region. It has a conserved serine/threonine kinase domain within its amino terminus and a large C-terminal region. Disease-causing mutations are distributed in both the amino terminal domain and in the large C-terminal domain. We have screened the CDKL5 gene in 44 patients with atypical Rett syndrome who had tested negative for MECP2 gene mutations and have identified 6 sequence variants, out of which three were novel and three known mutations. Two of these novel mutations p.V966I and p.A1011V were missense and p.H589H a silent mutation. Other known mutations identified were p.V999M, p.Q791P and p.T734A. Sequence homology for all the mutations revealed that the two mutations (p.Q791P and p.T734A) were conserved across species. This indicated the importance of these residues in structure and function of the protein. The damaging effects of these mutations were analysed in silico using PolyPhen-2 online software. The PolyPhen-2 scores of p.Q791P and p.T734A were 0.998 and 0.48, revealing that these mutations could be deleterious and might have potential functional effect. All other mutations had a low score suggesting that they might not alter the activity of CDKL5. We have also analysed the position of the mutations in the CDKL5 protein and found that all the mutations were present in the C-terminal domain of the protein. The C-terminal domain is required for

A qualitative investigation of recovery after femoral fracture in Rett syndrome

PubMed Central

Horne, Thomas; Leonard, Helen; Stannage, Katherine; Downs, Jenny

2016-01-01

BACKGROUND Children with severe disability often develop osteoporosis and have an increased risk of fracture. In Rett syndrome, the prevalence of fracture is four times greater than in the general population and the femur is commonly affected. This study used qualitative methods to investigate the regaining of mobility within 12 months following femoral fracture in Rett syndrome and parent caregiver experiences. METHODS Caregivers (n=14) of cases registered with the Australian Rett Syndrome Database with a daughter with Rett syndrome were recruited if their daughter sustained a femoral fracture between 2009 and 2014. Median (IQR) age at fracture was 11 years 4 months (8 years 8 months to 22 years 3 months). Qualitative methods were used to investigate parent/caregiver experiences and their daughter’s recovery following fracture. Themes in the interview data were identified with thematic analysis. RESULTS Operative management was chosen for those walking independently and non-operative management for most of the remaining. All who walked independently and one of the four who required assistance recovered pre-operative walking skills within 6 months. Themes identified by caregivers related to the complexities of pain recognition, the caregiver emotional journey and later rebuilding of relationships with service providers. CONCLUSIONS Those who walked with assistance were vulnerable to loss of this skill. Difficulties in pain recognition increased time to diagnose fracture and the acute episode was associated with heightened caregiver stress. Service providers can use family-centred practice models to support the strengthening of family functioning following this acute event that is surprisingly common in those with severe disability. PMID:27511284

International Rett Syndrome Foundation

MedlinePlus

... of families and professionals. Sign up Join RettSyndrome.org Join our community to receive updates from the ... 2520 International: 1-513-874-3020 admin@rettsyndrome.org EIN 31-1682518 CFC 11046 Newsroom PSA Press ...

How can clinical ethics guide the management of comorbidities in the child with Rett syndrome?

PubMed

Downs, Jenny; Forbes, David; Johnson, Michael; Leonard, Helen

2016-08-01

Rett syndrome is a rare disorder caused by a mutation in the MECP2 gene. Those affected generally have severe functional impairments, and medical comorbidities such as scoliosis and poor growth are common. There is a paucity of information on the natural history of many rare disorders and an even greater deficit of evidence to guide best practice. The population-based and longitudinal Australian Rett Syndrome Database established in 1993 has supported investigations of the natural history of Rett syndrome and effectiveness of treatments. This paper reviews the disorder Rett syndrome and evidence for the management of scoliosis and poor growth within a clinical ethics framework. Compared with conservative management, we have shown that spinal fusion is associated with reduced mortality and better respiratory health. We have also shown that gastrostomy insertion is associated with subsequent weight gain. Family counselling for both procedures necessarily must include family perspectives and careful clinical attention to their needs and wishes. Vignettes describing family decision-making and experiences are presented to illustrate the principals of beneficence and autonomy in determining the best interests of the child and family. A blend of evidence-based practice with a strong clinical ethics framework has capacity to build existing strengths in families and reduce the negative impacts of disability and in so doing, optimise the health and wellbeing of those with Rett syndrome. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Mutations in Epilepsy and Intellectual Disability Genes in Patients with Features of Rett Syndrome

PubMed Central

Olson, Heather E.; Tambunan, Dimira; LaCoursiere, Christopher; Goldenberg, Marti; Pinsky, Rebecca; Martin, Emilie; Ho, Eugenia; Khwaja, Omar; Kaufmann, Walter E.; Poduri, Annapurna

2017-01-01

Rett syndrome and neurodevelopmental disorders with features overlapping this syndrome frequently remain unexplained in patients without clinically identified MECP2 mutations. We recruited a cohort of 11 patients with features of Rett syndrome and negative initial clinical testing for mutations in MECP2. We analyzed their phenotypes to determine whether patients met formal criteria for Rett syndrome, reviewed repeat clinical genetic testing, and performed exome sequencing of the probands. Using 2010 diagnostic criteria, three patients had classical Rett syndrome, including two for whom repeat MECP2 gene testing had identified mutations. In a patient with neonatal onset epilepsy with atypical Rett syndrome, we identified a frameshift deletion in STXBP1. Among seven patients with features of Rett syndrome not fulfilling formal diagnostic criteria, four had suspected pathogenic mutations, one each in MECP2, FOXG1, SCN8A, and IQSEC2. MECP2 mutations are highly correlated with classical Rett syndrome. Genes associated with atypical Rett syndrome, epilepsy, or intellectual disability should be considered in patients with features overlapping with Rett syndrome and negative MECP2 testing. While most of the identified mutations were apparently de novo, the SCN8A variant was inherited from an unaffected parent mosaic for the mutation, which is important to note for counseling regarding recurrence risks. PMID:25914188

Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome.

PubMed

Olson, Heather E; Tambunan, Dimira; LaCoursiere, Christopher; Goldenberg, Marti; Pinsky, Rebecca; Martin, Emilie; Ho, Eugenia; Khwaja, Omar; Kaufmann, Walter E; Poduri, Annapurna

2015-09-01

Rett syndrome and neurodevelopmental disorders with features overlapping this syndrome frequently remain unexplained in patients without clinically identified MECP2 mutations. We recruited a cohort of 11 patients with features of Rett syndrome and negative initial clinical testing for mutations in MECP2. We analyzed their phenotypes to determine whether patients met formal criteria for Rett syndrome, reviewed repeat clinical genetic testing, and performed exome sequencing of the probands. Using 2010 diagnostic criteria, three patients had classical Rett syndrome, including two for whom repeat MECP2 gene testing had identified mutations. In a patient with neonatal onset epilepsy with atypical Rett syndrome, we identified a frameshift deletion in STXBP1. Among seven patients with features of Rett syndrome not fulfilling formal diagnostic criteria, four had suspected pathogenic mutations, one each in MECP2, FOXG1, SCN8A, and IQSEC2. MECP2 mutations are highly correlated with classical Rett syndrome. Genes associated with atypical Rett syndrome, epilepsy, or intellectual disability should be considered in patients with features overlapping with Rett syndrome and negative MECP2 testing. While most of the identified mutations were apparently de novo, the SCN8A variant was inherited from an unaffected parent mosaic for the mutation, which is important to note for counseling regarding recurrence risks. © 2015 Wiley Periodicals, Inc.

Bone mineral content and bone mineral density are lower in older than in younger females with Rett syndrome

USDA-ARS?s Scientific Manuscript database

Although bone mineral deficits have been identified in Rett syndrome (RTT), the prevalence of low bone mineral density (BMD) and its association with skeletal fractures and scoliosis has not been characterized fully in girls and women with RTT. Accordingly, we measured total body bone mineral conten...

Examination of X chromosome markers in Rett syndrome: Exclusion mapping with a novel variation on multilocus linkage analysis

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

Ellison, K.A.; Fill, C.P.; Terwililger, J.

Rett syndrome is a neurologic disorder characterized by early normal development followed by regression, acquired deceleration of head growth, autism, ataxia, and sterotypic hand movements. The exclusive occurrence of the syndrome in females and the occurrence of a few familial cases with inheritance through maternal lines suggest that this disorder is most likely secondary to a mutation on the X chromosome. To address this hypothesis and to identify candidate regions for the Rett syndrome gene locus, genotypic analysis was performed in two families with maternally related affected half-sisters by using 63 DNA markers from the X chromosome. Nineteen of themore » loci studied were chosen for multipoint linkage analysis because they have been previously genetically mapped using a large number of meioses from reference families. Using the exclusion criterion of a lod score less than [minus]2, the authors were able to exclude the region between the Duchenne muscular dystrophy locus and the DXS456 locus. This region extends from Xp21.2 to Xq21-q23. The use of the multipoint linkage analysis approach outlined in this study should allow the exclusion of additional regions of the X chromosome as new markers are analyzed.« less

Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies.

PubMed

Guerrini, Renzo; Parrini, Elena

2012-12-01

Rett syndrome is an X-linked neurodevelopmental disorder that manifests in early childhood with developmental stagnation, and loss of spoken language and hand use, with the development of distinctive hand stereotypies, severe cognitive impairment, and autistic features. About 60% of patients have epilepsy. Seizure onset before the age of 3 years is unlikely, and onset after age 20 is rare. Diagnosis of Rett syndrome is based on key clinical elements that identify "typical" Rett syndrome but also "variant" or "atypical" forms. Diagnostic criteria have been modified only slightly over time, even after discovering that MECP2 gene alterations are present in >90% of patients with typical Rett syndrome but only in 50-70% of atypical cases. Over the last several years, intragenic or genomic alterations of the CDKL5 and FOXG1 genes have been associated with severe cognitive impairment, early onset epilepsy and, often, dyskinetic movement disorders, which have variably been defined as Rett variants. It is now clearly emerging that epilepsy has distinctive characteristics in typical Rett syndrome and in the different syndromes caused by CDKL5 and FOXG1 gene alterations. The progressive parting of CDKL5- and FOXG1-gene-related encephalopathies from the core Rett syndrome is reflected by the effort to produce clearer diagnostic criteria for typical and atypical Rett syndrome. Efforts to characterize the molecular pathology underlying these developmental encephalopathies are pointing to abnormalities of telencephalic development, neuronal morphogenesis, maturation and maintenance, and dendritic arborization. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

SATB2-associated syndrome presenting with Rett-like phenotypes.

PubMed

Lee, J S; Yoo, Y; Lim, B C; Kim, K J; Choi, M; Chae, J-H

2016-06-01

The SATB2-associated syndrome (SAS) was proposed recently, after the SATB2 gene was initially discovered to be associated with isolated cleft palate. This syndrome is characterized by intellectual disability with delayed speech development, facial dysmorphism, cleft or high-arched palate, and dentition problems. Here, we describe two novel SATB2 sequence variants in two unrelated patients presenting with Rett-like phenotypes. We performed trio-based whole-exome sequencing in a 17-month-old girl presenting with severe retardation and Rett-like phenotypes, which revealed a de novo missense variant in SATB2 (p.Glu396Gln). Moreover, targeted sequencing of the SATB2 gene was performed in a 2-year-old girl with severe psychomotor retardation, facial hypotonia, and cleft palate who also exhibited some features of Rett syndrome. A nonsense variant in SATB2 was identified in this patient (p.Arg459*). This study expanded the clinical and genetic spectrum of SAS. SATB2 variants should be considered in cases with psychomotor retardation alone or in any cases with Rett-like phenotypes, regardless of the typical features of SAS such as cleft palate. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dysphagia in Rett Syndrome: A Descriptive Study.

PubMed

Mezzedimi, Chiara; Livi, Walter; De Felice, Claudio; Cocca, Serena

2017-09-01

Rett syndrome (RS) is a neurodevelopmental disorder and the second major cause of mental retardation in females. The aim of this study was to evaluate swallowing problems of RS patients by endoscopic assessment and compile a list of suggestions for managing feeding and preventing complications. The sample consisted of 61 female patients (mean age = 13.6 years, range, 2-33 years) admitted to the Department of Neuropsychiatry, where they had previously been diagnosed with RS. Speech evaluation associated with observation during mealtimes was useful to formulate suggestions for caregivers. Progressive deterioration of feeding was commonly noted by caregivers. Fifty-four patients had a history of recurrent episodes of bronchitis. Oral apraxia, dyskinetic tongue movements, prolonged oral stage, and poor bolus formation were the most common findings in all patients. Dysphagia was primarily limited to oral preparatory phases, while the pharyngeal phase was normal in most patients. The high percentage of dysphagia suggests the need to accurately monitor the feeding capability of RS children. It is critical to correctly inform caregivers about safe swallowing procedures to reduce the incidence of fatal complications.

People with "MECP2" Mutation-Positive Rett Disorder Who Converse

ERIC Educational Resources Information Center

Kerr, A. M.; Archer, H. L.; Evans, J. C.; Prescott, R. J.; Gibbon, F.

2006-01-01

Background: People with useful speech after regression constitute a distinct group of those with mutation-positive Rett disorder, 6% (20/331) reported among mutation-positive people in the British Survey. We aimed to determine the physical, mental and genetic characteristics of this group and to gain insight into their experience of Rett syndrome.…

Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families.

PubMed

Hynes, Kim; Tarpey, Patrick; Dibbens, Leanne M; Bayly, Marta A; Berkovic, Samuel F; Smith, Raffaella; Raisi, Zahyia Al; Turner, Samantha J; Brown, Natasha J; Desai, Tarishi D; Haan, Eric; Turner, Gillian; Christodoulou, John; Leonard, Helen; Gill, Deepak; Stratton, Michael R; Gecz, Jozef; Scheffer, Ingrid E

2010-03-01

Epilepsy and mental retardation limited to females (EFMR) is an intriguing X-linked disorder affecting heterozygous females and sparing hemizygous males. Mutations in the protocadherin 19 (PCDH19) gene have been identified in seven unrelated families with EFMR. Here, we assessed the frequency of PCDH19 mutations in individuals with clinical features which overlap those of EFMR. We analysed 185 females from three cohorts: 42 with Rett syndrome who were negative for MECP2 and CDKL5 mutations, 57 with autism spectrum disorders, and 86 with epilepsy with or without intellectual disability. No mutations were identified in the Rett syndrome and autism spectrum disorders cohorts suggesting that despite sharing similar clinical characteristics with EFMR, PCDH19 mutations are not generally associated with these disorders. Among the 86 females with epilepsy (of whom 51 had seizure onset before 3 years), with or without intellectual disability, we identified two (2.3%) missense changes. One (c.1671C-->G, p.N557K), reported previously without clinical data, was found in two affected sisters, the first EFMR family without a multigenerational family history of affected females. The second, reported here, is a novel de novo missense change identified in a sporadic female. The change, p.S276P, is predicted to result in functional disturbance of PCDH19 as it affects a highly conserved residue adjacent to the adhesion interface of EC3 of PCDH19. This de novo PCDH19 mutation in a sporadic female highlights that mutational analysis should be considered in isolated instances of girls with infantile onset seizures and developmental delay, in addition to those with the characteristic family history of EFMR.

Rett Syndrome: A Focus on Gut Microbiota

PubMed Central

Borghi, Elisa; Borgo, Francesca; Severgnini, Marco; Savini, Miriam Nella; Casiraghi, Maria Cristina; Vignoli, Aglaia

2017-01-01

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder affecting 1 in 10,000 live female births. Changes in microbiota composition, as observed in other neurological disorders such as autism spectrum disorders, may account for several symptoms typically associated with RTT. We studied the relationship between disease phenotypes and microbiome by analyzing diet, gut microbiota, and short-chain fatty acid (SCFA) production. We enrolled eight RTT patients and 10 age- and sex-matched healthy women, all without dietary restrictions. The microbiota was characterized by 16S rRNA gene sequencing, and SCFAs concentration was determined by gas chromatographic analysis. The RTT microbiota showed a lower α diversity, an enrichment in Bacteroidaceae, Clostridium spp., and Sutterella spp., and a slight depletion in Ruminococcaceae. Fecal SCFA concentrations were similar, but RTT samples showed slightly higher concentrations of butyrate and propionate, and significant higher levels in branched-chain fatty acids. Daily caloric intake was similar in the two groups, but macronutrient analysis showed a higher protein content in RTT diets. Microbial function prediction suggested in RTT subjects an increased number of microbial genes encoding for propionate and butyrate, and amino acid metabolism. A full understanding of these critical features could offer new, specific strategies for managing RTT-associated symptoms, such as dietary intervention or pre/probiotic supplementation. PMID:28178201

Rett syndrome from bench to bedside: recent advances

PubMed Central

Ehinger, Yann; Matagne, Valerie; Villard, Laurent; Roux, Jean-Christophe

2018-01-01

Rett Syndrome is a severe neurological disorder mainly due to de novo mutations in the methyl-CpG-binding protein 2 gene ( MECP2). Mecp2 is known to play a role in chromatin organization and transcriptional regulation. In this review, we report the latest advances on the molecular function of Mecp2 and the new animal and cellular models developed to better study Rett syndrome. Finally, we present the latest innovative therapeutic approaches, ranging from classical pharmacology to correct symptoms to more innovative approaches intended to cure the pathology. PMID:29636907

Rett syndrome diagnostic criteria: lessons from the Natural History Study.

PubMed

Percy, Alan K; Neul, Jeffrey L; Glaze, Daniel G; Motil, Kathleen J; Skinner, Steven A; Khwaja, Omar; Lee, Hye-Seung; Lane, Jane B; Barrish, Judy O; Annese, Fran; McNair, Lauren; Graham, Joy; Barnes, Katherine

2010-12-01

Analysis of 819 participants enrolled in the Rett syndrome (RTT) Natural History Study validates recently revised diagnostic criteria. 765 females fulfilled 2002 consensus criteria for classic (653/85.4%) or variant (112/14.6%) RTT. All participants classified as classic RTT fulfilled each revised main criterion; supportive criteria were not uniformly present. All variant RTT participants met at least 3 of 6 main criteria in the 2002, 2 of 4 main criteria in the current format, and 5 of 11 supportive criteria in both. This analysis underscores the critical role of main criteria for classic RTT; variant RTT requires both main and supportive criteria.

Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome

PubMed Central

De Filippis, Bianca; Chiodi, Valentina; Adriani, Walter; Lacivita, Enza; Mallozzi, Cinzia; Leopoldo, Marcello; Domenici, Maria Rosaria; Fuso, Andrea; Laviola, Giovanni

2015-01-01

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family—crucially involved in the regulation of brain structural plasticity and cognitive processes—can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues RTT-related phenotypic alterations, motor coordination (Dowel test), spatial reference memory (Barnes maze test) and synaptic plasticity (hippocampal long-term-potentiation) in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein (rp) S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to 2 months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R. PMID:25926782

Modifying Adult Interactional Style as Positive Behavioural Intervention for a Child with Rett Syndrome.

ERIC Educational Resources Information Center

Evans, Ian M.; Meyer, Luanna H.

1999-01-01

A naturalistic behavioral assessment and intervention program over a 3-year period for a New Zealand girl (age 5) with Rett syndrome is described. The most significant reduction in hand mannerisms and other excess behaviors was related to positive social interactions and play that allowed for communication at the affective level. (Author/CR)

Rett syndrome: an overlooked diagnosis in women with stereotypic hand movements, psychomotor retardation, Parkinsonism, and dystonia?

PubMed

Roze, Emmanuel; Cochen, Valérie; Sangla, Sophie; Bienvenu, Thierry; Roubergue, Anne; Leu-Semenescu, Smaranda; Vidaihet, Marie

2007-02-15

Rett syndrome is an X-linked neurodevelopmental disorder resulting in profound psychomotor retardation. It is usually diagnosed by a pediatrician or pediatric neurologist. Adult neurologists may, therefore, overlook the possibility of Rett syndrome in women with psychomotor retardation of unknown etiology. We report the case of a woman diagnosed with Rett syndrome at age 49 years. This report emphasizes the diagnostic value of movement disorders, including hand stereotypies, Parkinsonism, and dystonia, in adults with Rett syndrome.

Analysis of the parental origin of de novo MECP2 mutations and X chromosome inactivation in 24 sporadic patients with Rett syndrome in China.

PubMed

Zhu, Xingwang; Li, Meirong; Pan, Hong; Bao, Xinhua; Zhang, Jingjing; Wu, Xiru

2010-07-01

Rett syndrome is an X-linked neurodevelopmental disorder that predominantly affects females. It is caused by mutations in methyl-CpG-binding protein 2 gene. Due to the sex-limited expression, it has been suggested that de novo X-linked mutations may exclusively occur in male germ cells and thus only females are affected. In this study, the authors have analyzed the parental origin of mutations and the X-chromosome inactivation status in 24 sporadic patients with identified methyl-CpG-binding protein 2 gene mutations. The results showed that 22 of 24 patients have a paternal origin. Only 2 patients have a maternal origin. Except for 2 cases which were homozygotic at the androgen receptor gene locus, of the remaining 22 cases, 16 cases have a random X-chromosome inactivation pattern; the other 6 cases have a skewed X-chromosome inactivation and they favor expression of the wild allele. The relationship between X-chromosome inactivation and phenotype may need more cases to explore.

Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome.

PubMed

Ward, Christopher S; Huang, Teng-Wei; Herrera, José A; Samaco, Rodney C; Pitcher, Meagan R; Herron, Alan; Skinner, Steven A; Kaufmann, Walter E; Glaze, Daniel G; Percy, Alan K; Neul, Jeffrey L

2016-01-01

Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized.

Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome

PubMed Central

Ward, Christopher S.; Huang, Teng-Wei; Herrera, José A.; Samaco, Rodney C.; Pitcher, Meagan R.; Herron, Alan; Skinner, Steven A.; Kaufmann, Walter E.; Glaze, Daniel G.; Percy, Alan K.; Neul, Jeffrey L.

2016-01-01

Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized. PMID:27828991

Rett syndrome: basic features of visual processing-a pilot study of eye-tracking.

PubMed

Djukic, Aleksandra; Valicenti McDermott, Maria; Mavrommatis, Kathleen; Martins, Cristina L

2012-07-01

Consistently observed "strong eye gaze" has not been validated as a means of communication in girls with Rett syndrome, ubiquitously affected by apraxia, unable to reply either verbally or manually to questions during formal psychologic assessment. We examined nonverbal cognitive abilities and basic features of visual processing (visual discrimination attention/memory) by analyzing patterns of visual fixation in 44 girls with Rett syndrome, compared with typical control subjects. To determine features of visual fixation patterns, multiple pictures (with the location of the salient and presence/absence of novel stimuli as variables) were presented on the screen of a TS120 eye-tracker. Of the 44, 35 (80%) calibrated and exhibited meaningful patterns of visual fixation. They looked longer at salient stimuli (cartoon, 2.8 ± 2 seconds S.D., vs shape, 0.9 ± 1.2 seconds S.D.; P = 0.02), regardless of their position on the screen. They recognized novel stimuli, decreasing the fixation time on the central image when another image appeared on the periphery of the slide (2.7 ± 1 seconds S.D. vs 1.8 ± 1 seconds S.D., P = 0.002). Eye-tracking provides a feasible method for cognitive assessment and new insights into the "hidden" abilities of individuals with Rett syndrome. Copyright © 2012 Elsevier Inc. All rights reserved.

A case of a Tunisian Rett patient with a novel double-mutation of the MECP2 gene

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

Fendri-Kriaa, Nourhene, E-mail: nourhene.fendri@gmail.com; Hsairi, Ines; Kifagi, Chamseddine

2011-06-03

Highlights: {yields} Sequencing of the MECP2 gene, modeling and comparison of the two variants were performed in a Tunisian classical Rett patient. {yields} A double-mutation: a new and de novo mutation c.535C > T and the common one c.763C > T of the MECP2 gene was identified. {yields} The P179S transition may change local electrostatic properties which may affect the function and stability of the protein MeCP2. -- Abstract: Rett syndrome is an X-linked dominant disorder caused frequently by mutations in the methyl-CpG-binding protein 2 gene (MECP2). Rett patients present an apparently normal psychomotor development during the first 6-18 monthsmore » of life. Thereafter, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. The aim of this study was to perform a mutational analysis of the MECP2 gene in a classical Rett patient by sequencing the corresponding gene and modeling the found variants. The results showed the presence of a double-mutation: a new and de novo mutation c.535C > T (p.P179S) and the common c.763C > T (p.R255X) transition of the MECP2 gene. The p.P179S mutation was located in a conserved amino acid in CRIR domain (corepressor interacting region). Modeling results showed that the P179S transition could change local electrostatic properties by adding a negative charge due to serine hydroxyl group of this region of MeCP2 which may affect the function and stability of the protein. The p.R255X mutation is located in TRD-NLS domain (transcription repression domain-nuclear localization signal) of MeCP2 protein.« less

Contributing to the early detection of Rett syndrome: the potential role of auditory Gestalt perception.

PubMed

Marschik, Peter B; Einspieler, Christa; Sigafoos, Jeff

2012-01-01

To assess whether there are qualitatively deviant characteristics in the early vocalizations of children with Rett syndrome, we had 400 native Austrian-German speakers listen to audio recordings of vocalizations from typically developing girls and girls with Rett syndrome. The audio recordings were rated as (a) inconspicuous, (b) conspicuous or (c) not able to decide between (a) and (b). The results showed that participants were accurate in differentiating the vocalizations of typically developing children compared to children with Rett syndrome. However, the accuracy for rating verbal behaviors was dependent on the type of vocalization with greater accuracy for canonical babbling compared to cooing vocalizations. The results suggest a potential role for the use of rating child vocalizations for early detection of Rett syndrome. This is important because clinical criteria related to speech and language development remain important for early identification of Rett syndrome. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rett syndrome: update of a 25 year follow-up investigation in Western Sweden--sociomedical aspects.

PubMed

Berg, M; Hagberg, B

2001-12-01

Through 1998-1999 the Swedish research team have systematically mapped 45 of 54 females with Rett syndrome (RS) aged 5-57 years (Berg M. Uppföljning av flickor med Rett syndrom i Västsverige. Socialmedicinsk kartläggning, Stencilerad rapport, Sahlgrenska universitetssjukhuset, Göteborg, 1999; Läkartidningen (Swedish Medical Journal) 96 (1999) 5488). The emphasis is on the RS females' adjustment to grown-up living. At an adult age the large majority moved over to a Swedish type of small group home. We visited these girls in their group homes and got information about their adaptation to this special home situation. We noted their behaviour and contact with the staff and interviewed their parents. The results showed that the young women usually had adjusted well. The adjustment seemed to depend on the degree of planning before the girls moved from their parents to special group homes. These seem to provide a good environment for the RS females, in respect of both physical and social aspects. Although neuropaediatrics in Sweden today has advanced in RS knowledge, the result from this research shows that in Swedish society there is still a great ignorance of RS, even among medical professionals. In particular there is a gap of knowledge when the medical responsibility had to be transferred over to adult medicine. Many of the parents emphasized the great importance of how they were listened to by professionals in public medical and social services. It is essential that professionals always listen to information from parents and personal assistants.

Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes.

PubMed

Chao, Hsiao-Tuan; Chen, Hongmei; Samaco, Rodney C; Xue, Mingshan; Chahrour, Maria; Yoo, Jong; Neul, Jeffrey L; Gong, Shiaoching; Lu, Hui-Chen; Heintz, Nathaniel; Ekker, Marc; Rubenstein, John L R; Noebels, Jeffrey L; Rosenmund, Christian; Zoghbi, Huda Y

2010-11-11

Mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2), cause Rett syndrome and several neurodevelopmental disorders including cognitive disorders, autism, juvenile-onset schizophrenia and encephalopathy with early lethality. Rett syndrome is characterized by apparently normal early development followed by regression, motor abnormalities, seizures and features of autism, especially stereotyped behaviours. The mechanisms mediating these features are poorly understood. Here we show that mice lacking Mecp2 from GABA (γ-aminobutyric acid)-releasing neurons recapitulate numerous Rett syndrome and autistic features, including repetitive behaviours. Loss of MeCP2 from a subset of forebrain GABAergic neurons also recapitulates many features of Rett syndrome. MeCP2-deficient GABAergic neurons show reduced inhibitory quantal size, consistent with a presynaptic reduction in glutamic acid decarboxylase 1 (Gad1) and glutamic acid decarboxylase 2 (Gad2) levels, and GABA immunoreactivity. These data demonstrate that MeCP2 is critical for normal function of GABA-releasing neurons and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes.

Aerophagia and subcutaneous emphysema in a patient with Rett syndrome.

PubMed

Clark, Christine M; Shah-Becker, Shivani; Mathew, Abraham; Goyal, Neerav

2018-03-01

A patient with Rett syndrome presented to our Emergency Department with extensive subcutaneous emphysema in the cervical region, chest wall, upper extremities, and back. Diagnostic evaluation revealed a mucosal tear in the posterior pharyngeal wall and an abscessed retropharyngeal lymph node, but she had no known history of trauma to account for these findings. This report discusses the occurrence of subcutaneous emphysema in the context of a rare neurodevelopmental disorder and proposes accentuated aerophagia, a sequela of Rett syndrome, as the most likely underlying mechanism.

What Are the Treatments for Rett Syndrome?

MedlinePlus

... NICHD Research Information Find a Study More Information Cerebral Palsy Condition Information NICHD Research Information Find a Study ... www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002503 United Cerebral Palsy. (2009). Can Rett syndrome be treated? Retrieved June ...

Profiling Early Socio-Communicative Development in Five Young Girls with the Preserved Speech Variant of Rett Syndrome

ERIC Educational Resources Information Center

Marschik, Peter B.; Kaufmann, Walter E.; Einspieler, Christa; Bartl-Pokorny, Katrin D.; Wolin, Thomas; Pini, Giorgio; Budimirovic, Dejan B.; Zappella, Michele; Sigafoos, Jeff

2012-01-01

Rett syndrome (RTT) is a developmental disorder characterized by regression of purposeful hand skills and spoken language, although some affected children retain some ability to speech. We assessed the communicative abilities of five young girls, who were later diagnosed with the preserved speech variant of RTT, during the pre-regression period…

Rett syndrome treatment in mouse models: searching for effective targets and strategies.

PubMed

Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni

2013-05-01

Rett syndrome (RTT) is a pervasive developmental disorder, primarily affecting girls with a prevalence of 1 in every 10,000 births; it represents the second most common cause of intellectual disability in females. Mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2) have been identified as clear etiological factors in more than 90% of classical RTT cases. Whereas the mechanisms leading to the severe, progressive and specific neurological dysfunctions when this gene is mutated still remain to be elucidated, a series of different mouse models have been generated, bearing different Mecp2 mutation. Neurobehavioural analysis in these mouse lines have been carried out and phenotyping analysis can be now utilised to preclinically evaluate the effects of potential RTT treatments. This review summarizes the different results achieved in this research field taking into account different key targets identified to ameliorate RTT phenotype in mouse models, including those not directly downstream of MeCP2 and those limited to the early phases of postnatal development. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

PubMed Central

Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C.

2015-01-01

Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

Nosology and Diagnosis of Rett Syndrome

ERIC Educational Resources Information Center

Matson, Johnny L.; Fodstad, Jill C.; Boisjoli, Jessica A.

2008-01-01

Rett Syndrome is one of the least commonly occurring autism spectrum disorders (ASD), but certainly one of the most devastating. A genetic profile has been identified, but checklists still have an important role for prescreening, especially before expensive genetic testing, and to provide precise strengths and weaknesses with respect to the core…

Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes.

PubMed

Ito-Ishida, Aya; Ure, Kerstin; Chen, Hongmei; Swann, John W; Zoghbi, Huda Y

2015-11-18

Inhibitory neurons are critical for proper brain function, and their dysfunction is implicated in several disorders, including autism, schizophrenia, and Rett syndrome. These neurons are heterogeneous, and it is unclear which subtypes contribute to specific neurological phenotypes. We deleted Mecp2, the mouse homolog of the gene that causes Rett syndrome, from the two most populous subtypes, parvalbumin-positive (PV+) and somatostatin-positive (SOM+) neurons. Loss of MeCP2 partially impairs the affected neuron, allowing us to assess the function of each subtype without profound disruption of neuronal circuitry. We found that mice lacking MeCP2 in either PV+ or SOM+ neurons have distinct, non-overlapping neurological features: mice lacking MeCP2 in PV+ neurons developed motor, sensory, memory, and social deficits, whereas those lacking MeCP2 in SOM+ neurons exhibited seizures and stereotypies. Our findings indicate that PV+ and SOM+ neurons contribute complementary aspects of the Rett phenotype and may have modular roles in regulating specific behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical phenotype of 5 females with a CDKL5 mutation.

PubMed

Stalpers, Xenia L; Spruijt, Liesbeth; Yntema, Helger G; Verrips, Aad

2012-01-01

Mutations in the X-linked cyclin dependent kinase like 5 (CDKL5) gene have been reported in approximately 80 patients since the first description in 2003. The clinical presentation partly corresponds with Rett syndrome, considering clinical features as intellectual disability, hypotonia, and poor visual, language, and motor development. However, these patients do not meet the consensus criteria for Rett syndrome since they lack the clear period of regression. Furthermore, in contrast to Rett syndrome, patients with CDKL5 mutations, have seizures or infantile spasms starting in the first weeks of life. We present clinical phenotype of 5 girls having a mutation in the CDKL5 gene. All mutations are novel and are pathogenic since they either lead to a frameshift in the reading frame or affect a consensus splice site. Four of the mutations are detected de novo in the affected girl.

A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.

PubMed

Sartori, Stefano; Di Rosa, Gabriella; Polli, Roberta; Bettella, Elisa; Tricomi, Giovanni; Tortorella, Gaetano; Murgia, Alessandra

2009-02-01

Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures. (c) 2009 Wiley-Liss, Inc.

Investigation of Rett syndrome using pluripotent stem cells.

PubMed

Dajani, Rana; Koo, Sung-Eun; Sullivan, Gareth J; Park, In-Hyun

2013-11-01

Rett syndrome (RTT) is one of most prevalent female neurodevelopmental disorders. De novo mutations in X-linked MECP2 are mostly responsible for RTT. Since the identification of MeCP2 as the underlying cause of RTT, murine models have contributed to understanding the pathophysiology of RTT and function of MeCP2. Reprogramming is a procedure to produce induced pluripotent stem cells (iPSCs) by overexpression of four transcription factors. iPSCs obtain similar features as embryonic stem cells and are capable of self-renewing and differentiating into cells of all three layers. iPSCs have been utilized in modeling human diseases in vitro. Neurons differentiated from RTT-iPSCs showed the recapitulation of RTT phenotypes. Despite the early success, genetic and epigenetic instability upon reprogramming and ensuing maintenance of iPSCs raise concerns in using RTT-iPSCs as an accurate in vitro model. Here, we update the current iPSC-based RTT modeling, and its concerns and challenges. © 2013 Wiley Periodicals, Inc.

Attention and Communication in Rett Syndrome

ERIC Educational Resources Information Center

Fabio, Rosa Angela; Antonietti, Alessandro; Castelli, Ilaria; Marchetti, Antonella

2009-01-01

The study of selective attention and its influence on communication in patients with Rett Syndrome (RS), in which communication abilities are impaired is particularly relevant. The aim of this study was to analyse attention and communication abilities in RS. A sample of 20 children (10 girls with RS and 10 control girls, matched on mental age)…

The Rett syndrome in males.

PubMed

Philippart, M

1990-01-01

Two young males in their thirties are reported with a clinical history and examination indistinguishable from typical females with the Rett syndrome. Both had normal early development. The first patient had a regression by the end of the second year. He was late in walking, had prominent hand-wringing from the age of 4 years, and non-progressive dystonia from the age of 14 years. He is still ambulatory. Seizures which started at the age of 18 months have been easily controlled. The second patient has had a severe seizure disorder since the age of 7 months. In his early teens, he lost ambulation and his height and weight fell below the 2nd percentile. He has severe foot dystonia without spasticity. Both patients have a normal head size and no evidence of atrophy on a CT scan of the brain. Both had kyphoscoliosis in their teens. It is difficult to evaluate the incidence of such cases. Little attention being paid to the normal early development, they hide behind vague diagnoses such as cerebral palsy, static encephalopathy, and behavior disorder. Dystonia is often confused with spasticity, the lack of paralysis is not appreciated, apraxia and hand wringing are assumed to be self-stimulatory behaviors.

Low Bone Mineral Mass Is Associated with Decreased Bone Formation and Diet in Females with Rett Syndrome

PubMed Central

Motil, Kathleen J.; Barrish, Judy O.; Neul, Jeffrey L.; Glaze, Daniel G.

2014-01-01

Objective To characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of females with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Methods Total body bone mineral content (BMC) and density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Results Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z-scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and gender, showed significant positive associations with total body BMD z-scores. Conclusion This study suggests decreased bone formation rather than increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium and phosphorus intakes may offer an opportunity to improve bone health in RTT. PMID:25144778

Molecular Screening of "MECP2" Gene in a Cohort of Lebanese Patients Suspected with Rett Syndrome: Report on a Mild Case with a Novel Indel Mutation

ERIC Educational Resources Information Center

Corbani, S.; Chouery, E.; Fayyad, J.; Fawaz, A.; El Tourjuman, O.; Badens, C.; Lacoste, C.; Delague, V.; Megarbane, A.

2012-01-01

Background: Rett syndrome (RTT), an X-linked, dominant, neurodevelopment disorder represents 10% of female subjects with profound intellectual disability. Mutations in the "MECP2" gene are responsible for up to 95% of the classical RTT cases, and nearly 500 different mutations distributed throughout the gene have been reported. Methods:…

Assessment of Caregiver Inventory for Rett Syndrome

ERIC Educational Resources Information Center

Lane, Jane B.; Salter, Amber R.; Jones, Nancy E.; Cutter, Gary; Horrigan, Joseph; Skinner, Steve A.; Kaufmann, Walter E.; Glaze, Daniel G.; Neul, Jeffrey L.; Percy, Alan K.

2017-01-01

Rett syndrome (RTT) requires total caregiver attention and leads to potential difficulties throughout life. The Caregiver Burden Inventory, designed for Alzheimer disease, was modified to a RTT Caregiver Inventory Assessment (RTT CIA). Reliability and face, construct, and concurrent validity were assessed in caregivers of individuals with RTT. Chi…

Using eye-tracking technology for communication in Rett syndrome: perceptions of impact.

PubMed

Vessoyan, Kelli; Steckle, Gill; Easton, Barb; Nichols, Megan; Mok Siu, Victoria; McDougall, Janette

2018-04-27

Studies have investigated the use of eye-tracking technology to assess cognition in individuals with Rett syndrome, but few have looked at this access method for communication for this group. Loss of speech, decreased hand use, and severe motor apraxia significantly impact functional communication for this population. Eye gaze is one modality that may be used successfully by individuals with Rett syndrome. This multiple case study explored whether using eye-tracking technology, with ongoing support from a team of augmentative and alternative communication (AAC) therapists, could help four participants with Rett syndrome meet individualized communication goals. Two secondary objectives were to examine parents' perspectives on (a) the psychosocial impact of their child's use of the technology, and (b) satisfaction with using the technology. All four participants were rated by the treating therapists to have made improvement on their goals. According to both quantitative findings and descriptive information, eye-tracking technology was viewed by parents as contributing to participants' improved psychosocial functioning. Parents reported being highly satisfied with both the device and the clinical services received. This study provides initial evidence that eye-tracking may be perceived as a worthwhile and potentially satisfactory technology to support individuals with Rett syndrome in communicating. Future, more rigorous research that addresses the limitations of a case study design is required to substantiate study findings.

Contributing to the Early Detection of Rett Syndrome: The Potential Role of Auditory Gestalt Perception

ERIC Educational Resources Information Center

Marschik, Peter B.; Einspieler, Christa; Sigafoos, Jeff

2012-01-01

To assess whether there are qualitatively deviant characteristics in the early vocalizations of children with Rett syndrome, we had 400 native Austrian-German speakers listen to audio recordings of vocalizations from typically developing girls and girls with Rett syndrome. The audio recordings were rated as (a) inconspicuous, (b) conspicuous or…

Communication Intervention in Rett Syndrome: A Systematic Review

ERIC Educational Resources Information Center

Sigafoos, Jeff; Green, Vanessa A.; Schlosser, Ralf; O'eilly, Mark F.; Lancioni, Giulio E.; Rispoli, Mandy; Lang, Russell

2009-01-01

We reviewed communication intervention studies involving people with Rett syndrome. Systematic searches of five electronic databases, selected journals, and reference lists identified nine studies meeting the inclusion criteria. These studies were evaluated in terms of: (a) participant characteristics, (b) target skills, (c) procedures, (d) main…

Community participation for girls and women living with Rett syndrome.

PubMed

Andrews, Jaimi; Leonard, Helen; Hammond, Geoffrey C; Girdler, Sonya; Rajapaksa, Ruwani; Bathgate, Katherine; Downs, Jenny

2014-01-01

To describe the relationships between impairment and contextual factors and community participation for girls and women with Rett syndrome. Data was collected from a questionnaire completed in 2009 by families participating in the Australian Rett Syndrome Database (n = 214). Univariate and multivariate logistic regression were used to analyse relationships between impairment, personal and environmental factors and community participation. The mean age of the girls and women was 17.6 years (SD = 7.95, range 3 to 34 years) with 114 (53.3%) girls still at school and 100 (46.7%) women post school. Frequency of activities was influenced by level of walking, community support and maternal education. For girls living at home, participation in activities was associated with greater functional independence and higher levels of maternal education. Participation in recreational (90.1%), physical/skill-based (67.6%) and/or social (70.3%) activities was commonly reported by families, while self-improvement (17.6%) activities were less reported. Younger girls participated in activities mainly with family members and older girls more frequently participated with carers. Participation for girls and women with Rett syndrome could be enhanced by stronger local community supports. There are also needs for the implementation of policies that ensure resources are available and accessible by those communities most in need.

Measuring Use and Cost of Health Sector and Related Care in a Population of Girls and Young Women with Rett Syndrome

ERIC Educational Resources Information Center

Hendrie, Delia; Bebbington, Ami; Bower, Carol; Leonard, Helen

2011-01-01

This study measured use and cost of health sector and related services in Rett syndrome and effects of socio-demographic, clinical severity and genetic factors on costs. The study population consisted of individuals with Rett syndrome registered with the Australian Rett Syndrome Database in 2004. Descriptive analysis was used to examine patterns…

Activities that girls and women with Rett syndrome liked or did not like to do.

PubMed

Sernheim, Åsa-Sara; Hemmingsson, Helena; Witt Engerström, Ingegerd; Liedberg, Gunilla

2016-11-06

Activities occur in all people's lives. This study investigated over a period of time, 15 years, what activities were enjoyed or not enjoyed and what activities parents and staff liked to do with girls/women with Rett syndrome. A descriptive study was conducted using secondary data from three earlier questionnaires at the Swedish National Rett Center. The first questionnaire provided data on 123 girls/women with Rett syndrome, the second on 52 and the third questionnaire, on 39. Informants were parents and/or staff, in total 365. Open-ended questions were analysed using a content analysis approach. Three categories appeared: Being in motion, receiving impressions and having contact. Bathing/swimming, listening to music and being outdoors/walking were the most enjoyed activities over the years. Of the few activities that were reported as being unenjoyable, most were daily care activities. The activities that the parents/staff enjoyed doing with the girls/women were similar to those the girls/women themselves liked to do. A preliminary overview for both liked and disliked activities of girls/women with Rett syndrome was presented. This knowledge could facilitate the choice and use of activities.

Daily affect and female sexual function.

PubMed

Kalmbach, David A; Pillai, Vivek

2014-12-01

The specific affective experiences related to changes in various aspects of female sexual function have received little attention as most prior studies have focused instead on the role of clinical mood and anxiety disorders and their influence on sexual dysfunction. We sought to understand the transaction between daily affect and female sexual function in effort to provide a more nuanced understanding of the interplay between affective and sexual experiences. The present study used a 2-week daily diary approach to examine same-day and temporal relations between positive and negative affect states and sexual function in young women. We examined the unique relations between positive (i.e., joviality, serenity, self-assurance) and negative (i.e., fear, sadness, hostility) affects and female sexual response (i.e., desire, subjective arousal, vaginal lubrication, orgasmic function, and sexual pain) while controlling for higher order sexual distress, depression, and anxiety, as well as age effects and daily menstruation. Analyses revealed different aspects of both positive and negative affects to be independently related to sexual response indices. Specifically, results indicated that joviality was related to same-day sexual desire and predicted increased desire the following day. This latter relation was partially mediated by sexual activity. Further, greater sexual desire predicted next-day calmness, which was partially mediated by sexual activity. Notably, fear was related to same-day subjective arousal, lubrication, orgasmic function, and vaginal pain, whereas poorer orgasmic function predicted greater next-day sadness. These findings describe the manner in which changes in affect correspond to variations in female sexual function, thus highlighting the inextricability of mental and sexual health. Further, these findings may offer insight into the progression of normative levels of affect and sexual function as they develop into comorbid depression, anxiety, and

[Role of mitochondrial lesion in pathogenesis of sporadic rett syndrome].

PubMed

Meng, H; Pan, H; Qi, Y

2001-06-10

To investigate the role of mitochondrial lesion in children with Rett syndrome (RTT). The platelets from 6 cases with Rett syndrome and 9 normal controls were fused with mitochondrial DNA-lacking rho degrees cell by polyethylene glycol-mediated fusion technique. The oxygen free radical was evaluated by the polarography with substrates of vitamine C and TMPD (N, N, N', N'-tetramethyl-p-phenlene diamine). The rate of apoptosis was determinated by flow cytometry. The apoptosis was observed by electronic microscope and TUNEL method. The t test between groups was adopted in study. In RTT patients, the anticyano-respiration significantly increased by 23% (t = 4.76, P < 0.01). After 6-hour coincubation with 100 micromol/L H(2)O(2), the rate of apoptosis is (3.6 +/- 1.1) % in normal control, and (9.9 +/- 2.7) % in RTT group with significant difference (t = 6.30, P < 0.01), the existence of apoptosis was confirmed by electronic microscope and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL). After mitochondrial DNA transfer, the oxygen free radical increased in mitochondrial respiratory chain in cybrids of RTT children. RTT cybrid cell lines demonstrated an increased sensitivity to H(2)O(2)-induced apoptotic cell death as compared to control cybrids. The mitochondrial lesion might play a role in the pathogenesis of Rett syndrome.

Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study.

PubMed

Halbach, Nicky; Smeets, Eric E; Julu, Peter; Witt-Engerström, Ingegerd; Pini, Giorgio; Bigoni, Stefania; Hansen, Stig; Apartopoulos, Flora; Delamont, Robert; van Roozendaal, Kees; Scusa, Maria F; Borelli, Paolo; Candel, Math; Curfs, Leopold

2016-09-01

Many studies have attempted to establish the genotype-phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well-defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype-phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non-invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence-based management in RTT. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Seizures and pain uncertainty associated with parenting stress and Rett syndrome.

PubMed

Byiers, Breanne J; Tervo, Raymond C; Feyma, Timothy J; Symons, Frank J

2014-04-01

Data were collected parenting stress, adaptive behavior, pain, and health issues from the caregivers of 35 girls and women with Rett syndrome (mean age = 20.3). A majority (60%) of parents reported stress in the clinical range on at least 1 subscale of the Parenting Stress Index-Short Form. Seizures and uncertainty about their daughter's gastrointestinal pain experience were significantly associated with higher levels of parenting stress. No other child factors (adaptive behavior, age, residential status) were significantly related to parenting stress. Factors related to chronic health concerns (seizures, ambiguous pain presentation) may be important when considering family stress issues in relation to general outcomes for girls with Rett syndrome and related developmental disorders.

A qualitative motion analysis study of voluntary hand movement induced by music in patients with Rett syndrome

PubMed Central

Go, Tohshin; Mitani, Asako

2009-01-01

Patients with Rett syndrome are known to respond well to music irrespective of their physical and verbal disabilities. Therefore, the relationship between auditory rhythm and their behavior was investigated employing a two-dimensional motion analysis system. Ten female patients aged from three to 17 years were included. When music with a simple regular rhythm started, body rocking appeared automatically in a back and forth direction in all four patients who showed the same rocking motion as their stereotyped movement. Through this body rocking, voluntary movement of the hand increased gradually, and finally became sufficient to beat a tambourine. However, the induction of body rocking by music was not observed in the other six patients who did not show stereotyped body rocking in a back and forth direction. When the music stopped suddenly, voluntary movement of the hand disappeared. When the music changed from a simple regular rhythm to a continuous tone without an auditory rhythm, the periodic movement of both the hand and body prolonged. Auditory rhythm shows a close relationship with body movement and facilitates synchronized body movement. This mechanism was demonstrated to be preserved in some patients with Rett syndrome, and stimulation with music could be utilized for their rehabilitation. PMID:19851517

A qualitative motion analysis study of voluntary hand movement induced by music in patients with Rett syndrome.

PubMed

Go, Tohshin; Mitani, Asako

2009-01-01

Patients with Rett syndrome are known to respond well to music irrespective of their physical and verbal disabilities. Therefore, the relationship between auditory rhythm and their behavior was investigated employing a two-dimensional motion analysis system. Ten female patients aged from three to 17 years were included. When music with a simple regular rhythm started, body rocking appeared automatically in a back and forth direction in all four patients who showed the same rocking motion as their stereotyped movement. Through this body rocking, voluntary movement of the hand increased gradually, and finally became sufficient to beat a tambourine. However, the induction of body rocking by music was not observed in the other six patients who did not show stereotyped body rocking in a back and forth direction. When the music stopped suddenly, voluntary movement of the hand disappeared. When the music changed from a simple regular rhythm to a continuous tone without an auditory rhythm, the periodic movement of both the hand and body prolonged. Auditory rhythm shows a close relationship with body movement and facilitates synchronized body movement. This mechanism was demonstrated to be preserved in some patients with Rett syndrome, and stimulation with music could be utilized for their rehabilitation.

Functional Communication Training in Rett Syndrome: A Preliminary Study

ERIC Educational Resources Information Center

Byiers, Breanne J.; Dimian, Adele; Symons, Frank J.

2014-01-01

Rett syndrome (RTT) is associated with a range of serious neurodevelopmental consequences including severe communicative impairments. Currently, no evidence-based communication interventions exist for the population (Sigafoos et al., 2009). The purpose of the current study was to examine the effectiveness of functional assessment (FA) and…

Assessing cognitive functioning in females with Rett syndrome by eye-tracking methodology.

PubMed

Ahonniska-Assa, Jaana; Polack, Orli; Saraf, Einat; Wine, Judy; Silberg, Tamar; Nissenkorn, Andreea; Ben-Zeev, Bruria

2018-01-01

While many individuals with severe developmental impairments learn to communicate with augmentative and alternative communication (AAC) devices, a significant number of individuals show major difficulties in the effective use of AAC. Recent technological innovations, i.e., eye-tracking technology (ETT), aim to improve the transparency of communication and may also enable a more valid cognitive assessment. To investigate whether ETT in forced-choice tasks can enable children with very severe motor and speech impairments to respond consistently, allowing a more reliable evaluation of their language comprehension. Participants were 17 girls with Rett syndrome (M = 6:06 years). Their ability to respond by eye gaze was first practiced with computer games using ETT. Afterwards, their receptive vocabulary was assessed using the Peabody Picture Vocabulary Test-4 (PPVT-4). Target words were orally presented and participants responded by focusing their eyes on the preferred picture. Remarkable differences between the participants in receptive vocabulary were demonstrated using ETT. The verbal comprehension abilities of 32% of the participants ranged from low-average to mild cognitive impairment, and the other 68% of the participants showed moderate to severe impairment. Young age at the time of assessment was positively correlated with higher receptive vocabulary. The use of ETT seems to make the communicational signals of children with severe motor and communication impairments more easily understood. Early practice of ETT may improve the quality of communication and enable more reliable conclusions in learning and assessment sessions. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Updating the profile of C-terminal MECP2 deletions in Rett syndrome

PubMed Central

Bebbington, A; Percy, A; Christodoulou, J; Ravine, D; Ho, G; Jacoby, P; Anderson, A; Pineda, M; Ben Zeev, B; Bahi-Buisson, N; Smeets, E; Leonard, H

2014-01-01

Objectives This study aimed to compare the phenotype of Rett syndrome cases with C-terminal deletions to that of cases with different MECP2 mutations and to examine the phenotypic variation within C-terminal deletions. Methods Cases were selected from InterRett, an international database and from the population-based Australian Rett Syndrome Database. Cases (n=832) were included if they had a pathogenic MECP2 mutation in which the nature of the amino acid change was known. Three severity scale systems were used, and individual aspects of the phenotype were also compared. Results Lower severity was associated with C-terminal deletions (n=79) compared to all other MECP2 mutations (e.g. Pineda scale C-terminals mean 15.0 (95% CI 14.0–16.0) vs 16.2 (15.9–16.5). Cases with C-terminal deletions were more likely to have a normal head circumference (odds ratio 3.22, 95% CI 1.53 – 6.79) and weight (odds ratio 2.97, 95% CI 1.25–5.76). Onset of stereotypies tended to be later (median age 2.5 years vs 2 years, p<0.001 from survival analysis), and age of learning to walk tended to be earlier (median age 1.6 years vs 2 years, p=0.002 from survival analysis). Those with C-terminal deletions occurring later in the region had lower average severity scores than those occurring earlier in the region. Conclusion In terms of overall severity C-terminal deletion cases would appear to be in the middle of the range. In terms of individual aspects of phenotype growth and ability to ambulate appear to be particular strengths. By pooling data internationally this study has achieved the case numbers to provide a phenotypic profile of C-terminal deletions in Rett syndrome. PMID:19914908

Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome

PubMed Central

Engineer, Crystal T.; Rahebi, Kimiya C.; Borland, Michael S.; Buell, Elizabeth P.; Centanni, Tracy M.; Fink, Melyssa K.; Im, Kwok W.; Wilson, Linda G.; Kilgard, Michael P.

2015-01-01

Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial. PMID:26321676

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.

Changing the Perspective on Early Development of Rett Syndrome

ERIC Educational Resources Information Center

Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

2013-01-01

We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

Clinical Guidelines for Management of Bone Health in Rett Syndrome Based on Expert Consensus and Available Evidence

PubMed Central

Jefferson, Amanda; Leonard, Helen; Siafarikas, Aris; Woodhead, Helen; Fyfe, Sue; Ward, Leanne M.; Munns, Craig; Motil, Kathleen; Tarquinio, Daniel; Shapiro, Jay R.; Brismar, Torkel; Ben-Zeev, Bruria; Bisgaard, Anne-Marie; Coppola, Giangennaro; Ellaway, Carolyn; Freilinger, Michael; Geerts, Suzanne; Humphreys, Peter; Jones, Mary; Lane, Jane; Larsson, Gunilla; Lotan, Meir; Percy, Alan; Pineda, Mercedes; Skinner, Steven; Syhler, Birgit; Thompson, Sue; Weiss, Batia; Witt Engerström, Ingegerd; Downs, Jenny

2016-01-01

Objectives We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. Methods An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions. Results Agreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended. Conclusion A clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity. PMID:26849438

Clinical Guidelines for Management of Bone Health in Rett Syndrome Based on Expert Consensus and Available Evidence.

PubMed

Jefferson, Amanda; Leonard, Helen; Siafarikas, Aris; Woodhead, Helen; Fyfe, Sue; Ward, Leanne M; Munns, Craig; Motil, Kathleen; Tarquinio, Daniel; Shapiro, Jay R; Brismar, Torkel; Ben-Zeev, Bruria; Bisgaard, Anne-Marie; Coppola, Giangennaro; Ellaway, Carolyn; Freilinger, Michael; Geerts, Suzanne; Humphreys, Peter; Jones, Mary; Lane, Jane; Larsson, Gunilla; Lotan, Meir; Percy, Alan; Pineda, Mercedes; Skinner, Steven; Syhler, Birgit; Thompson, Sue; Weiss, Batia; Witt Engerström, Ingegerd; Downs, Jenny

2016-01-01

We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions. Agreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended. A clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity.

Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice

PubMed Central

Hao, Shuang; Tang, Bin; Wu, Zhenyu; Ure, Kerstin; Sun, Yaling; Tao, Huifang; Gao, Yan; Patel, Akash J.; Curry, Daniel J.; Samaco, Rodney C.; Zoghbi, Huda Y.; Tang, Jianrong

2016-01-01

Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnestic rats have demonstrated that DBS targeted to the fimbria-fornix1-3, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory3-5. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder (IDD). IDDs are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We hypothesized that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett Syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP26, RTT appears by the second year of life, causing profound impairment in cognitive, motor, and social skills along with an array of neurological features7; RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity8-11. Here we show that forniceal DBS in RTT mice rescued contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restored in vivo hippocampal long-term potentiation (LTP) and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT. PMID:26469053

Communication Assessment for Individuals with Rett Syndrome: A Systematic Review

ERIC Educational Resources Information Center

Sigafoos, Jeff; Kagohara, Debora; van der Meer, Larah; Green, Vanessa A.; O'Reilly, Mark F.; Lancioni, Giulio E.; Lang, Russell; Rispoli, Mandy; Zisimopoulos, Dimitrios

2011-01-01

We reviewed studies that aimed to determine whether behaviors, such as body movements, vocalizations, eye gaze, and facial expressions, served a communicative function for individuals with Rett syndrome. A systematic search identified eight studies, which were summarized in terms of (a) participants, (b) assessment targets, (c) assessment…

Development of the Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database and the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire.

PubMed

Santosh, Paramala; Lievesley, Kate; Fiori, Federico; Singh, Jatinder

2017-06-21

Rett syndrome (RTT) is a pervasive neurodevelopmental disorder that presents with deficits in brain functioning leading to language and learning regression, characteristic hand stereotypies and developmental delay. Different mutations in the gene implicated in RTT- methyl-CpG-binding protein 2 ( MECP2 ) establishes RTT as a disorder with divergent symptomatology ranging from individuals with severe to milder phenotypes. A reliable and single multidimensional questionnaire is needed that can embrace all symptoms, and the relationships between them, and can map clinically meaningful data to symptomatology across the lifespan in patients with RTT. As part of the HealthTracker-based Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database, the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire will be able to marry with the physiological aspects of the disease obtained using wearable sensor technology, along with genetic and psychosocial data to stratify patients. Taken together, the web-based TRIAL database will empower clinicians and researchers with the confidence to delineate between different aspects of disorder symptomatology to streamline care pathways for individuals or for those patients entering clinical trials. This protocol describes the anticipated development of the REST questionnaire and the TRIAL database which links with the outcomes of the wearable sensor technology, and will serve as a barometer for longitudinal patient monitoring in patients with RTT. The US Food and Drug Administration Guidance for Patient-Reported Outcome Measures will be used as a template to inform the methodology of the study. It will follow an iterative framework that will include item/concept identification, item/concept elicitation in parent/carer-mediated focus groups, expert clinician feedback, web-based presentation of questionnaires, initial scale development, instrument refinement and instrument validation. The study has received favourable

[The clinical phenomenology of Rett's syndrome].

PubMed

Calderón-González, R; Calderón-Sepulveda, R F; Treviño-Welsh, J

1999-01-01

The work was done to facilitate the clinical diagnosis and understanding of Rett syndrome (RS) by grouping the symptoms and signs in areas of neurological disfunction. This is a retrospective, longitudinal and observational study of 30 young females whose clinical manifestations were grouped using a modified Fitzgerald et al. scale for motor and behavior evaluation of patients with RS. All patients were videotaped at least during one or several appointments during their follow-up for a period of 1 to 10 years. All patients and videotapes were reviewed independently by the three authors. We followed the clinical diagnostic criteria of classic RS, and grouped the symptoms and signs in 12 groups of clinical phenomenology that represented specific areas of central or peripheral nervous system involvement: 1) dementia syndrome (fronto-temporo-parietal and limbic dysfunction); 2) extrapyramidal syndrome (basal ganglia dysfunction); 3) respiratory function disorders (brain stem reticular system disfunction); 4) sleep disorders (reticular system and limbic dysfunction); 5) epilepsy (cortico-subcortical paroxysmal bioelectrical dysfunction); 6) lower motor neuron syndrome (neuropathic dysfunction and/or peripheral neuropathy); 7) body growth retardation; 8) tonic-postural skeletal deformities; 9) deficit of pain sensation (nociceptive deficit); 10) pseudobulbar dysfunction; 11) autonomic dysfunction and 12) others (microcephaly and bruxism). In clinical practice, we recommend the use of this grouping of symptoms and signs because it makes facilities the clinical study, definition of areas of dysfunction and diagnosis of the patient with RS.

Brief Report:MECP2 Mutations in People without Rett Syndrome

ERIC Educational Resources Information Center

Suter, Bernhard; Treadwell-Deering, Diane; Zoghbi, Huda Y.; Glaze, Daniel G.; Neul, Jeffrey L.

2014-01-01

Mutations in "Methyl-CpG-Binding protein 2" ("MECP2") are commonly associated with the neurodevelopmental disorder Rett syndrome (RTT). However, some people with RTT do not have mutations in "MECP2," and interestingly there have been people identified with "MECP2" mutations that do not have the clinical…

Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications.

PubMed

Szafranski, Przemyslaw; Golla, Sailaja; Jin, Weihong; Fang, Ping; Hixson, Patricia; Matalon, Reuben; Kinney, Daniel; Bock, Hans-Georg; Craigen, William; Smith, Janice L; Bi, Weimin; Patel, Ankita; Wai Cheung, Sau; Bacino, Carlos A; Stankiewicz, Paweł

2015-07-01

Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8-21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540-935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8-14 years of age, and three affected girls, 6-8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly.

Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications

PubMed Central

Szafranski, Przemyslaw; Golla, Sailaja; Jin, Weihong; Fang, Ping; Hixson, Patricia; Matalon, Reuben; Kinney, Daniel; Bock, Hans-georg; Craigen, William; Smith, Janice L; Bi, Weimin; Patel, Ankita; Wai Cheung, Sau; Bacino, Carlos A; Stankiewicz, Paweł

2015-01-01

Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8–21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540–935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8–14 years of age, and three affected girls, 6–8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly. PMID:25315662

Quantification of functional abilities in Rett syndrome: a comparison between stages III and IV

PubMed Central

Monteiro, Carlos BM; Savelsbergh, Geert JP; Smorenburg, Ana RP; Graciani, Zodja; Torriani-Pasin, Camila; de Abreu, Luiz Carlos; Valenti, Vitor E; Kok, Fernando

2014-01-01

We aimed to evaluate the functional abilities of persons with Rett syndrome (RTT) in stages III and IV. The group consisted of 60 females who had been diagnosed with RTT: 38 in stage III, mean age (years) of 9.14, with a standard deviation of 5.84 (minimum 2.2/maximum 26.4); and 22 in stage IV, mean age of 12.45, with a standard deviation of 6.17 (minimum 5.3/maximum 26.9). The evaluation was made using the Pediatric Evaluation of Disability Inventory, which has 197 items in the areas of self-care, mobility, and social function. The results showed that in the area of self-care, stage III and stage IV RTT persons had a level of 24.12 and 18.36 (P=0.002), respectively. In the area of mobility, stage III had 37.22 and stage IV had 14.64 (P<0.001), while in the area of social function, stage III had 17.72 and stage IV had 12.14 (P=0.016). In conclusion, although persons with stage III RTT have better functional abilities when compared with stage IV, the areas of mobility, self-care, and social function are quite affected, which shows a great functional dependency and need for help in basic activities of daily life. PMID:25061307

Development of a Video-Based Evaluation Tool in Rett Syndrome

ERIC Educational Resources Information Center

Fyfe, S.; Downs, J.; McIlroy, O.; Burford, B.; Lister, J.; Reilly, S.; Laurvick, C. L.; Philippe, C.; Msall, M.; Kaufmann, W. E.; Ellaway, C.; Leonard, H.

2007-01-01

This paper describes the development of a video-based evaluation tool for use in Rett syndrome (RTT). Components include a parent-report checklist, and video filming and coding protocols that contain items on eating, drinking, communication, hand function and movements, personal care and mobility. Ninety-seven of the 169 families who initially…

Retracing Atypical Development: A Preserved Speech Variant of Rett Syndrome

ERIC Educational Resources Information Center

Marschik, Peter B.; Einspieler, Christa; Oberle, Andreas; Laccone, Franco; Prechtl, Heinz F. R.

2009-01-01

The subject of the present study is the development of a girl with the preserved speech variant of Rett disorder. Our data are based on detailed retrospective and prospective video analyses. Despite achieving developmental milestones, movement quality was already abnormal during the girl's first half year of life. In addition, early hand…

Management of epilepsy in patients with Rett syndrome: perspectives and considerations.

PubMed

Krajnc, Natalija

2015-01-01

Rett syndrome (RTT) is a common neurodevelopmental disorder that appears in infancy with regression of acquired motor skills, loss of purposeful activity, hand stereotypies, loss of acquired spoken language, and seizures. Epilepsy affects the majority of patients in a specific clinical stage of the disease and is drug resistant in approximately one-third of cases. The association of epilepsy and even drug-resistant epilepsy has been reported in certain genotypes of the methyl-CpG-binding protein 2 mutation, which is present in a majority of patients with classical RTT. The evolution of electroencephalographic abnormalities accompanying the clinical development of the syndrome is well described, but much less is known about the seizure semiology and the effectiveness of specific antiepileptic drugs. The aim of this review is to present the clinical and electrophysiological aspects of epilepsy in RTT and the current treatment approach.

The Relationship between "MECP2" Mutation Type and Health Status and Service Use Trajectories over Time in a Rett Syndrome Population

ERIC Educational Resources Information Center

Young, Deidra; Bebbington, Ami; de Klerk, Nick; Bower, Carol; Nagarajan, Lakshmi; Leonard, Helen

2011-01-01

This study aimed to investigate the trajectories over time of health status and health service use in Rett syndrome by mutation type. Data were obtained from questionnaires administered over 6 years to 256 participants from the Australian Rett Syndrome Database. Health status (episodes of illness and medication load) and health service use…

Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome

PubMed Central

Kunio, Miyake; Yang, Chunshu; Minakuchi, Yohei; Ohori, Kenta; Soutome, Masaki; Hirasawa, Takae; Kazuki, Yasuhiro; Adachi, Noboru; Suzuki, Seiko; Itoh, Masayuki; Goto, Yu-ichi; Andoh, Tomoko; Kurosawa, Hiroshi; Akamatsu, Wado; Ohyama, Manabu; Okano, Hideyuki; Oshimura, Mitsuo; Sasaki, Masayuki; Toyoda, Atsushi; Kubota, Takeo

2013-01-01

Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature and nurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. The twins shared the same de novo mutation in exon 4 of the MECP2 gene (G269AfsX288), which was paternal in origin and occurred during spermatogenesis. The XCI patterns in the twins did not differ in lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as does neuronal tissue). No reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues such as Mohawk Homeobox (MKX), Brain-type Creatine Kinase (CKB), and FYN Tyrosine Kinase Protooncogene (FYN). The level of methylation in these upstream regions was inversely correlated with the level of gene expression. Thus, differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins. PMID:23805272

Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome.

PubMed

Miyake, Kunio; Yang, Chunshu; Minakuchi, Yohei; Ohori, Kenta; Soutome, Masaki; Hirasawa, Takae; Kazuki, Yasuhiro; Adachi, Noboru; Suzuki, Seiko; Itoh, Masayuki; Goto, Yu-Ichi; Andoh, Tomoko; Kurosawa, Hiroshi; Oshimura, Mitsuo; Sasaki, Masayuki; Toyoda, Atsushi; Kubota, Takeo

2013-01-01

Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature and nurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. The twins shared the same de novo mutation in exon 4 of the MECP2 gene (G269AfsX288), which was paternal in origin and occurred during spermatogenesis. The XCI patterns in the twins did not differ in lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as does neuronal tissue). No reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues such as Mohawk Homeobox (MKX), Brain-type Creatine Kinase (CKB), and FYN Tyrosine Kinase Protooncogene (FYN). The level of methylation in these upstream regions was inversely correlated with the level of gene expression. Thus, differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins.

Spinal fusion for scoliosis in Rett syndrome with an emphasis on early postoperative complications.

PubMed

Gabos, Peter G; Inan, Muharrem; Thacker, Mihir; Borkhu, Buttugs

2012-01-15

Retrospective case-control study. To examine the postoperative complications of posterior spinal fusion in a population of patients with Rett syndrome (RS). Scoliosis is a common feature of RS, a progressive neurologic disorder affecting almost exclusively females. Despite this, there is little published information regarding the surgical treatment of scoliosis in this disorder. Sixteen consecutive female patients with RS treated by posterior spinal fusion and unit rod instrumentation for progressive scoliosis between 1995 and 2003 were evaluated. Only patients with a minimum of 2-year follow-up were included. Preoperative medical conditions and postoperative complications were recorded. As a control group, we randomly selected 32 spastic quadriplegic patients who underwent the identical procedure during the same time period, selected from our database and matched according to age, level of neurologic impairment, and medical complexity. There was a high rate of early medical complications in the RS patients, with 28 major and 37 minor complications. Only 1 patient did not have a major medical complication, and every patient had at least 1 minor gastrointestinal and/or respiratory complication. Major respiratory complications occurred in 10 patients (63%) and comprised 61% of all major complications. Major gastrointestinal complications occurred in 6 patients (37%) and comprised 21% of all major complications. Other major complications included disseminated intravascular coagulopathy (1 patient), subacute bacterial endocarditis (1 patient), sacral decubiti requiring surgical debridement (2 patients), and extensive bilateral heterotopic ossification of the hips (1 patient). There were no cases of instrumentation failure, pseudarthrosis, deep infection, or need for rod revision. Postoperative complication scores were similar to those in patients with spastic quadriplegic pattern cerebral palsy. Spinal fusion for scoliosis in RS can give a satisfactory technical result

Gastrostomy placement improves height and weight gain in girls with Rett syndrome

USDA-ARS?s Scientific Manuscript database

Growth failure and undernutrition complicate the clinical course of girls with Rett syndrome (RTT). These abnormalities are, in part, the consequence of oral motor dysfunction and inadequate dietary intake. We hypothesized that gastrostomy placement for nutritional therapy reverses the decline in he...

Social Impairments in Rett Syndrome: Characteristics and Relationship with Clinical Severity

ERIC Educational Resources Information Center

Kaufmann, W. E.; Tierney, E.; Rohde, C. A.; Suarez-Pedraza, M. C.; Clarke, M. A.; Salorio, C. F.; Bibat, G.; Bukelis, I.; Naram, D.; Lanham, D. C.; Naidu, S.

2012-01-01

Background: While behavioural abnormalities are fundamental features of Rett syndrome (RTT), few studies have examined the RTT behavioural phenotype. Most of these reports have focused on autistic features, linked to the early regressive phase of the disorder, and few studies have applied standardised behavioural measures. We used a battery of…

Expression profiling of clonal lymphocyte cell cultures from Rett syndrome patients

USDA-ARS?s Scientific Manuscript database

More than 85% of Rett syndrome (RTT) patients have heterozygous mutations in the X-linked MECP2 gene which encodes methyl-CpG-binding protein 2, a transcriptional repressor that binds methylated CpG sites. Because MECP2 is subject to X chromosome inactivation (XCI), girls with RTT express either the...

Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

PubMed

Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

2016-01-01

The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.

Peculiarities in the Gestural Repertoire: An Early Marker for Rett Syndrome?

ERIC Educational Resources Information Center

Marschik, Peter B.; Sigafoos, Jeff; Kaufmann, Walter E.; Wolin, Thomas; Talisa, Victor B.; Bartl-Pokorny, Katrin D.; Budimirovic, Dejan B.; Vollmann, Ralf; Einspieler, Christa

2012-01-01

We studied the gestures used by children with classic Rett syndrome (RTT) to provide evidence as to how this essential aspect of communicative functions develops. Seven participants with RTT were longitudinally observed between 9 and 18 months of life. The gestures used by these participants were transcribed and coded from a retrospective analysis…

Suggestions for Educational and Therapeutic Interventions with the Rett Syndrome Child.

ERIC Educational Resources Information Center

International Rett Syndrome Association, Inc., Fort Washington, MD.

This paper comprises a compilation of nine case studies of girls (aged 4-16 years) with Rett Syndrome. The educational settings involved are various and include private day school, public elementary school in both integrated and special needs classrooms, and a county-operated preschool program for handicapped children. Each case study outlines the…

Cognitive-Affective Dimensions of Female Orgasm: The Role of Automatic Thoughts and Affect During Sexual Activity.

PubMed

Tavares, Inês M; Laan, Ellen T M; Nobre, Pedro J

2017-06-01

Cognitive-affective factors contribute to female sexual dysfunctions, defined as clinically significant difficulties in the ability to respond sexually or to experience sexual pleasure. Automatic thoughts and affect presented during sexual activity are acknowledged as maintenance factors for these difficulties. However, there is a lack of studies on the influence of these cognitive-affective dimensions regarding female orgasm. To assess the role of automatic thoughts and affect during sexual activity in predicting female orgasm occurrence and to investigate the mediator role of these variables in the relation between sexual activity and orgasm occurrence. Nine hundred twenty-six sexually active heterosexual premenopausal women reported on frequency of sexual activities and frequency of orgasm occurrence, cognitive factors, and social desirability. Participants completed the Sexual Modes Questionnaire-Automatic Thoughts Subscale, the Positive and Negative Affect Schedule, and the Socially Desirable Response Set. Multiple linear regressions and mediation analyses were performed, controlling for the effect of covariates such as social desirability, sociodemographic and medical characteristics, and relationship factors. The main outcome measurement was orgasm frequency as predicted and mediated by automatic thoughts and affect experienced during sexual activities. The presence of failure thoughts and lack of erotic thoughts during sexual activity significantly and negatively predicted female orgasm, whereas positive affect experienced during sexual activity significantly and positively predicted female orgasm. Moreover, negative automatic thoughts and positive affect during sexual activity were found to mediate the relation between sexual activity and female orgasm occurrence. These data suggest that the cognitive aspects of sexual involvement are critical to enhancing female orgasm experience and can aid the development of strategies that contemplate the central role

The eye-tracking of social stimuli in patients with Rett syndrome and autism spectrum disorders: a pilot study.

PubMed

Schwartzman, José Salomão; Velloso, Renata de Lima; D'Antino, Maria Eloísa Famá; Santos, Silvana

2015-05-01

To compare visual fixation at social stimuli in Rett syndrome (RT) and autism spectrum disorders (ASD) patients. Visual fixation at social stimuli was analyzed in 14 RS female patients (age range 4-30 years), 11 ASD male patients (age range 4-20 years), and 17 children with typical development (TD). Patients were exposed to three different pictures (two of human faces and one with social and non-social stimuli) presented for 8 seconds each on the screen of a computer attached to an eye-tracker equipment. Percentage of visual fixation at social stimuli was significantly higher in the RS group compared to ASD and even to TD groups. Visual fixation at social stimuli seems to be one more endophenotype making RS to be very different from ASD.

Socio-Economic Affects of Floods on Female Teachers in Jampur (Pakistan)

ERIC Educational Resources Information Center

Buzdar, Muhammad Ayub; Ali, Akhtar

2011-01-01

Women are major affected segment of society in any disaster in under developed countries. Floods of 2010, in Pakistan, affected more than 17 million people. Ultimately, it created several social, psychological and financial problems for affected females. The current paper aimed to study the socio-economic affects of floods on female teachers of…

Severe changes in colon epithelium in the Mecp2-null mouse model of Rett syndrome.

PubMed

Millar-Büchner, Pamela; Philp, Amber R; Gutierrez, Noemí; Villanueva, Sandra; Kerr, Bredford; Flores, Carlos A

2016-12-01

Rett syndrome is best known due to its severe and devastating symptoms in the central nervous system. It is produced by mutations affecting the Mecp2 gene that codes for a transcription factor. Nevertheless, evidence for MECP2 activity has been reported for tissues other than those of the central nervous system. Patients affected by Rett presented with intestinal affections whose origin is still not known. We have observed that the Mecp2-null mice presented with episodes of diarrhea, and decided to study the intestinal phenotype in these mice. Mecp2-null mice or bearing the conditional intestinal deletion of MECP2 were used. Morphometirc and histologic analysis of intestine, and RT-PCR, western blot and immunodetection were perfomed on intestinal samples of the animals. Electrical parameters of the intestine were determined by Ussing chamber experiments in freshly isolated colon samples. First we determined that MECP2 protein is mainly expressed in cells of the lower part of the colonic crypts and not in the small intestine. The colon of the Mecp2-null mice was shorter than that of the wild-type. Histological analysis showed that epithelial cells of the surface have abnormal localization of key membrane proteins like ClC-2 and NHE-3 that participate in the electroneutral NaCl absorption; nevertheless, electrogenic secretion and absorption remain unaltered. We also detected an increase in a proliferation marker in the crypts of the colon samples of the Mecp2-null mice, but the specific silencing of Mecp2 from intestinal epithelium was not able to recapitulate the intestinal phenotype of the Mecp2-null mice. In summary, we showed that the colon is severely affected by Mecp2 silencing in mice. Changes in colon length and epithelial histology are similar to those observed in colitis. Changes in the localization of proteins that participate in fluid absorption can explain watery stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce colon

Vitamin D deficiency is prevalent in girls and women with rett syndrome

USDA-ARS?s Scientific Manuscript database

The aim of the study was to determine the prevalence of vitamin D deficiency and identify the relation between 25-hydroxyvitamin D (25-(OH)D) levels and the consumption of dietary sources of vitamin D or exposure to anticonvulsants in girls and women with Rett syndrome (RTT). Retrospective review of...

Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists

PubMed Central

Abdala, Ana P.; Bissonnette, John M.; Newman-Tancredi, Adrian

2014-01-01

Rett syndrome is a neurological disorder caused by loss of function of methyl-CpG-binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional regulator has a devastating effect on the central nervous system. One of the most severe and life-threatening presentations of this syndrome is brainstem dysfunction, which results in autonomic disturbances such as breathing deficits, typified by episodes of breathing cessation intercalated with episodes of hyperventilation or irregular breathing. Defects in numerous neurotransmitter systems have been observed in Rett syndrome both in animal models and patients. Here we dedicate special attention to serotonin due to its role in promoting regular breathing, increasing vagal tone, regulating mood, alleviating Parkinsonian-like symptoms and potential for therapeutic translation. A promising new symptomatic strategy currently focuses on regulation of serotonergic function using highly selective serotonin type 1A (5-HT1A) “biased agonists.” We address this newly emerging therapy for respiratory brainstem dysfunction and challenges for translation with a holistic perspective of Rett syndrome, considering potential mood and motor effects. PMID:24910619

Novel mutation in forkhead box G1 (FOXG1) gene in an Indian patient with Rett syndrome.

PubMed

Das, Dhanjit Kumar; Jadhav, Vaishali; Ghattargi, Vikas C; Udani, Vrajesh

2014-03-15

Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by the progressive loss of intellectual functioning, fine and gross motor skills and communicative abilities, deceleration of head growth, and the development of stereotypic hand movements, occurring after a period of normal development. The classic form of RTT involves mutation in MECP2 while the involvement of CDKL5 and FOXG1 genes has been identified in atypical RTT phenotype. FOXG1 gene encodes for a fork-head box protein G1, a transcription factor acting primarily as transcriptional repressor through DNA binding in the embryonic telencephalon as well as a number of other neurodevelopmental processes. In this report we have described the molecular analysis of FOXG1 gene in Indian patients with Rett syndrome. FOXG1 gene mutation analysis was done in a cohort of 34 MECP2/CDKL5 mutation negative RTT patients. We have identified a novel mutation (p. D263VfsX190) in FOXG1 gene in a patient with congenital variant of Rett syndrome. This mutation resulted into a frameshift, thereby causing an alteration in the reading frames of the entire coding sequence downstream of the mutation. The start position of the frameshift (Asp263) and amino acid towards the carboxyl terminal end of the protein was found to be well conserved across species using multiple sequence alignment. Since the mutation is located at forkhead binding domain, the resultant mutation disrupts the secondary structure of the protein making it non-functional. This is the first report from India showing mutation in FOXG1 gene in Rett syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

Rett syndrome: EEG presentation.

PubMed

Robertson, R; Langill, L; Wong, P K; Ho, H H

1988-11-01

Rett syndrome, a degenerative neurological disorder of girls, has a classical presentation and typical EEG findings. The electroencephalograms (EEGs) of 7 girls whose records have been followed from the onset of symptoms to the age of 5 or more are presented. These findings are tabulated with the Clinical Staging System of Hagberg and Witt-Engerström (1986). The records show a progressive deterioration in background rhythms in waking and sleep. The abnormalities of the background activity may only become evident at 4-5 years of age or during stage 2--the Rapid Destructive Stage. The marked contrast between waking and sleep background may not occur until stage 3--the Pseudostationary Stage. In essence EEG changes appear to lag behind clinical symptomatology by 1-3 years. An unexpected, but frequent, abnormality was central spikes seen in 5 of 7 girls. They appeared to be age related and could be evoked by tactile stimulation in 2 patients. We hypothesize that the prominent 'hand washing' mannerism may be self-stimulating and related to the appearance of central spike discharges.

Unconventional Transcriptional Response to Environmental Enrichment in a Mouse Model of Rett Syndrome

PubMed Central

Kerr, Bredford; Silva, Pamela A.; Walz, Katherina; Young, Juan I.

2010-01-01

Background Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2) and one of the leading causes of mental retardation in females. RTT is characterized by psychomotor retardation, purposeless hand movements, autistic-like behavior and abnormal gait. We studied the effects of environmental enrichment (EE) on the phenotypic manifestations of a RTT mouse model that lacks MeCP2 (Mecp2 −/y). Principal Findings We found that EE delayed and attenuated some neurological alterations presented by Mecp2 −/y mice and prevented the development of motor discoordination and anxiety-related abnormalities. To define the molecular correlate of this beneficial effect of EE, we analyzed the expression of several synaptic marker genes whose expression is increased by EE in several mouse models. Conclusions/Significance We found that EE induced downregulation of several synaptic markers, suggesting that the partial prevention of RTT-associated phenotypes is achieved through a non-conventional transcriptional program. PMID:20634955

How Stereotypes Affect Current Collegiate Female Athletes' Athletic Experiences

ERIC Educational Resources Information Center

James, Melissa

2017-01-01

Stereotype discrimination affects female athletes' athletic experiences. Studies have been conducted of former collegiate female athletes' perceptions of the lesbian stereotype found that they were discriminated against because of their sport participation. These limit the recalling of thoughts and experience from the female athletes' playing…

Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene.

PubMed

Vieira, José Pedro; Lopes, Fátima; Silva-Fernandes, Anabela; Sousa, Maria Vânia; Moura, Sofia; Sousa, Susana; Costa, Bruno M; Barbosa, Mafalda; Ylstra, Bauke; Temudo, Teresa; Lourenço, Teresa; Maciel, Patrícia

2015-11-01

Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome -46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated by the inversion. However, and in spite of a balanced pattern of X inactivation, this patient displayed hypomethylation and an overexpression of the MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55±0.38) in comparison to a group of control individuals; the expression of the CDKL5 gene was similar to that of controls (mean fold change: 0.98±0.10). No gains or losses were detected in the breakpoint regions encompassing known or suspected transcription regulatory elements. We propose that the de-regulation of MECP2 expression in this patient may be due to alterations in long-range genomic interactions caused by the inversion and hypothesize that this type of epigenetic de-regulation of the MECP2 may be present in other RTT-like patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessment and management of nutrition and growth in Rett syndrome

PubMed Central

Leonard, Helen; Ravikumara, Madhur; Baikie, Gordon; Naseem, Nusrat; Ellaway, Carolyn; Percy, Alan; Abraham, Suzanne; Geerts, Suzanne; Lane, Jane; Jones, Mary; Bathgate, Katherine; Downs, Jenny

2014-01-01

Objectives We developed recommendations for the clinical management of poor growth and weight gain in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. Methods Initial draft recommendations were created based upon literature review and 34 open-ended questions where the literature was lacking. Statements and questions were made available to an international, multi-disciplinary panel of clinicians in an online format and a Microsoft Word formatted version of the draft via email. Input was sought using a 2-stage modified Delphi process to reach consensus agreement. Items included clinical assessment of growth, anthropometry, feeding difficulties and management to increase caloric intake, decrease feeding difficulties and consideration of gastrostomy. Results Agreement was achieved on 101/112 statements. A comprehensive approach to the management of poor growth in Rett syndrome is recommended that takes into account factors such as feeding difficulties and nutritional needs. A BMI of approximately the 25th centile can be considered as a reasonable target in clinical practice. Gastrostomy is indicated for very poor growth, if there is risk of aspiration and if feeding times are prolonged. Conclusions These evidence- and consensus-based recommendations have the potential to improve care of nutrition and growth in a rare condition and stimulate research to improve the current limited evidence base. PMID:24084372

Sleep Disturbance in Children with Rett Syndrome: A Qualitative Investigation of the Parental Experience

ERIC Educational Resources Information Center

McDougall, Allyson; Kerr, Alison M.; Espie, Colin A.

2005-01-01

Background: Sleep problems in children with intellectual disability can be precipitated and maintained by intrinsic and external factors. The present study comprised a qualitative investigation of the experiences of parents of children with Rett syndrome, a neurodevelopmental disorder where sleep disturbance is common. Method: Audio-taped…

Physical and mental health of mothers caring for a child with Rett syndrome.

PubMed

Laurvick, Crystal L; Msall, Michael E; Silburn, Sven; Bower, Carol; de Klerk, Nicholas; Leonard, Helen

2006-10-01

Our goal was to investigate the physical and mental health of mothers who care for a child with Rett syndrome. We assessed maternal physical and mental health by using the SF-12 version 1 physical component summary and mental component summary scores as the outcome measures of interest. Mothers (n = 135) of children with Rett syndrome completed the SF-12 measure as part of the Australian Rett Syndrome Study in 2002. The analysis investigated linear relationships between physical and mental health scores and maternal, family, and child characteristics. Mothers ranged in age from 21 to 60 years and their children from 3 to 27 years. Nearly half of these mothers (47.4%) indicated that they worked full-time or part-time outside the home, and 41% had a combined family (gross) income of <40,000 Australian dollars. The resultant model for physical health demonstrated that the following factors were positively associated with better maternal physical health: the mother working full-time or part-time outside the home, having some high school education, having private health insurance, the child not having breathing problems in the last 2 years, the child not having home-based structured therapy, and high scores on the Family Resource Scale (indicating adequacy of time resources for basic and family needs). The resultant model for mental health demonstrated that the following factors were positively associated with better maternal mental health: the mother working full-time or part-time outside the home, the child not having a fracture in the last 2 years, lesser reporting of facial stereotypes and involuntary facial movements, being in a well-adjusted marriage, and having low stress scores. Our study suggests that the most important predictors of maternal physical and emotional health are child behavior, caregiver demands, and family function.

Assessment of Caregiver Inventory for Rett Syndrome

PubMed Central

Lane, Jane B.; Salter, Amber R.; Jones, Nancy E.; Cutter, Gary; Horrigan, Joseph; Skinner, Steve A.; Kaufmann, Walter E.; Glaze, Daniel G.; Neul, Jeffrey L.; Percy, Alan K.

2017-01-01

Rett syndrome (RTT) requires total caregiver attention and leads to potential difficulties throughout life. The Caregiver Burden Inventory, designed for Alzheimer disease, was modified to a RTT Caregiver Inventory Assessment (RTT CIA). Reliability and face, construct, and concurrent validity were assessed in caregivers of individuals with RTT. Chi-square or Fisher’s exact test for categorical variables and t-tests or Wilcoxon two-sample tests for continuous variables were utilized. Survey completed by 198 caregivers; 70 caregivers completed follow-up assessment. Exploratory factor analysis revealed good agreement for Physical Burden, Emotional Burden, and Social Burden. Internal reliability was high (Cronbach’s alpha: 0.898). RTT CIA represents a reliable and valid measure, providing a needed metric of caregiver burden in this disorder. PMID:28132121

Gastrostomy placement favorably alters the natural history of growth failure and undernutrition in Rett syndrome

USDA-ARS?s Scientific Manuscript database

Growth failure and undernutrition complicate the clinical course of girls with Rett syndrome (RTT). These abnormalities are, in part, the consequence of oral motor dysfunction and inadequate dietary intake. Our objective was to determine if gastrostomy placement for nutritional therapy alters the na...

Rett-like phenotypes: expanding the genetic heterogeneity to the KCNA2 gene and first familial case of CDKL5-related disease.

PubMed

Allou, L; Julia, S; Amsallem, D; El Chehadeh, S; Lambert, L; Thevenon, J; Duffourd, Y; Saunier, A; Bouquet, P; Pere, S; Moustaïne, A; Ruaud, L; Roth, V; Jonveaux, P; Philippe, C

2017-03-01

Several genes have been implicated in Rett syndrome (RTT) in its typical and variant forms. We applied next-generation sequencing (NGS) to evaluate for mutations in known or new candidate genes in patients with variant forms of Rett or Rett-like phenotypes of unknown molecular aetiology. In the first step, we used NGS with a custom panel including MECP2, CDKL5, FOXG1, MEF2C and IQSEC2. In addition to a FOXG1 mutation in a patient with all core features of the congenital variant of RTT, we identified a missense (p.Ser240Thr) in CDKL5 in a patient who appeared to be seizure free. This missense was maternally inherited with opposite allele expression ratios in the proband and her mother. In the asymptomatic mother, the mutated copy of the CDKL5 gene was inactivated in 90% of blood cells. We also identified a premature stop codon (p.Arg926*) in IQSEC2 in a patient with a Rett-like phenotype. Finally, exome sequencing enabled us to characterize a heterozygous de novo missense (p.Val408Ala) in KCNA2 encoding the potassium channel Kv 1.2 in a girl with infantile-onset seizures variant of RTT. Our study expands the genetic heterogeneity of RTT and RTT-like phenotypes. Moreover, we report the first familial case of CDKL5-related disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Physical and Mental Health of Mothers Caring for a Child with Rett Syndrome

ERIC Educational Resources Information Center

Laurvick, Crystal L.; Msall, Michael E.; Silburn, Sven; Bower, Carol; de Klerk, Nicholas; Leonard, Helen

2007-01-01

Objectives: Our goal was to investigate the physical and mental health of mothers who care for a child with Rett syndrome. Methods: We assessed maternal physical and mental health by using the SF-12 version 1 physical component summary and mental component summary scores as the outcome measures of interest. Mothers (n = 135) of children with Rett…

Clinical severity and quality of life in children and adolescents with Rett syndrome

PubMed Central

Lane, J.B.; Lee, H.-S.; Smith, L.W.; Cheng, P.; Glaze, D.G.; Neul, J.L.; Motil, K.J.; Barrish, J.O.; Skinner, S.A.; Annese, F.; McNair, L.; Graham, J.; Khwaja, O.; Barnes, K.; Krischer, J.P.

2011-01-01

Objective: The clinical features and genetics of Rett syndrome (RTT) have been well studied, but examination of quality of life (QOL) is limited. This study describes the impact of clinical severity on QOL among female children and adolescents with classic RTT. Methods: Cross-sectional and longitudinal analyses were conducted on data collected from an NIH-sponsored RTT natural history study. More than 200 participants from 5 to 18 years of age with classic RTT finished their 2-year follow-up at the time of analysis. Regression models after adjustment for their MECP2 mutation type and age at enrollment were used to examine the association between clinical status and QOL. Results: Severe clinical impairment was highly associated with poor physical QOL, but worse motor function and earlier age at onset of RTT stereotypies were associated with better psychosocial QOL; conversely, better motor function was associated with poorer psychosocial QOL. Conclusions: Standard psychosocial QOL assessment for children and adolescents with RTT differs significantly with regard to their motor function severity. As clinical trials in RTT emerge, the Child Health Questionnaire 50 may represent one of the important outcome measures. PMID:22013176

Scoliosis in Rett Syndrome: Progression, Comorbidities, and Predictors.

PubMed

Killian, John T; Lane, Jane B; Lee, Hye-Seung; Skinner, Steve A; Kaufmann, Walter E; Glaze, Daniel G; Neul, Jeffrey L; Percy, Alan K

2017-05-01

Scoliosis is prominent in Rett syndrome (RTT). Following the prior report from the US Natural History Study, the onset and progression of severe scoliosis (≥40° Cobb angle) and surgery were examined regarding functional capabilities and specific genotypes, addressing the hypothesis that abnormal muscle tone, poor oral feeding, puberty, and delays or absence of sitting balance and ambulation may be responsible for greater risk in RTT. The multicenter RTT Natural History Study gathered longitudinal data for classic RTT, including mutation type, scoliosis, muscle tone, sitting, ambulation, hand function, and feeding. Cox regression models were used to examine the association between scoliosis and functional characteristics. All analyses utilized SAS 9.4; two-sided P values of <0.05 were considered significant. A total of 913 females with classic RTT were included. Scoliosis frequency and severity increased with age. Severe scoliosis was found in 251 participants (27%), 113 of whom developed severe scoliosis during the follow-up assessments; 168 (18%) had surgical correction. Severe MECP2 mutations (R106W, R168X, R255X, R270X, and large deletions) showed a higher proportion of scoliosis. Individuals developing severe scoliosis or requiring surgery were less likely to sit, ambulate, or use their hands and were more likely to have begun puberty. Significant differences were absent for epilepsy rates, sleep problems, or constipation. Scoliosis requires vigilance regarding the risk factors noted, particularly specific mutations and the role of puberty and motor abilities. Bracing is recommended for moderate curves and surgery for severe curves in accordance with published guidelines for scoliosis management. Copyright © 2017 Elsevier Inc. All rights reserved.

Dendritic spine dysgenesis in Rett syndrome

PubMed Central

Xu, Xin; Miller, Eric C.; Pozzo-Miller, Lucas

2014-01-01

Spines are small cytoplasmic extensions of dendrites that form the postsynaptic compartment of the majority of excitatory synapses in the mammalian brain. Alterations in the numerical density, size, and shape of dendritic spines have been correlated with neuronal dysfunction in several neurological and neurodevelopmental disorders associated with intellectual disability, including Rett syndrome (RTT). RTT is a progressive neurodevelopmental disorder associated with intellectual disability that is caused by loss of function mutations in the transcriptional regulator methyl CpG-binding protein 2 (MECP2). Here, we review the evidence demonstrating that principal neurons in RTT individuals and Mecp2-based experimental models exhibit alterations in the number and morphology of dendritic spines. We also discuss the exciting possibility that signaling pathways downstream of brain-derived neurotrophic factor (BDNF), which is transcriptionally regulated by MeCP2, offer promising therapeutic options for modulating dendritic spine development and plasticity in RTT and other MECP2-associated neurodevelopmental disorders. PMID:25309341

Attentional and affective biases for attractive females emerge early in development.

PubMed

Rennels, Jennifer Lynn; Verba, Stephanie Ann

2017-01-01

Predominant experience with females early in development results in infants developing an attractive, female-like facial representation that guides children's attention toward and affective preferences for attractive females. When combined with increased interest in the other sex at puberty, these early emerging biases might help explain the robust prosocial and financial biases men exhibit toward attractive women during adulthood.

Rett Syndrome: Crossing the Threshold to Clinical Translation

PubMed Central

Katz, David M.; Bird, Adrian; Coenraads, Monica; Gray, Steven J.; Menon, Debashish U.; Philpot, Benjamin D.; Tarquinio, Daniel C.

2016-01-01

Lying at the intersection between neurobiology and epigenetics, Rett syndrome (RTT) has garnered intense interest in recent years, not only from a broad range of academic scientists, but also from the pharmaceutical and biotechnology industries. In addition to the critical need for treatments for this devastating disorder, optimism for developing RTT treatments derives from a unique convergence of factors, including a known monogenic cause, reversibility of symptoms in preclinical models, a strong clinical research infrastructure highlighted by an NIH-funded natural history study and well-established clinics with significant patient populations. Here, we review recent advances in understanding the biology of RTT, particularly promising preclinical findings, lessons from past clinical trials, and critical elements of trial design for rare disorders. PMID:26830113

Expression pattern of cdkl5 during zebrafish early development: implications for use as model for atypical Rett syndrome.

PubMed

Vitorino, Marta; Cunha, Nídia; Conceição, Natércia; Cancela, M Leonor

2018-05-11

Atypical Rett syndrome is a child neurodevelopmental disorder induced by mutations in CDKL5 gene and characterized by a progressive regression in development with loss of purposeful use of the hands, slowed brain and head growth, problems with walking, seizures, and intellectual disability. At the moment, there is no cure for this pathology and little information is available concerning animal models capable of mimicking its phenotypes, thus the development of additional animal models should be of interest to gain more knowledge about the disease. Zebrafish has been used successfully as model organism for many human genetic diseases; however, no information is available concerning the spatial and temporal expression of cdkl5 orthologous in this organism. In the present study, we identified the developmental expression patterns of cdkl5 in zebrafish by quantitative PCR and whole-mount in situ hybridization. cdkl5 is expressed maternally at low levels during the first 24 h of development. After that the expression of the gene increases significantly and it starts to be expressed mainly in the nervous system and in several brain structures, such as telencephalon, mesencephalon and diencephalon. The expression patterns of cdkl5 in zebrafish is in accordance with the tissues known to be affected in humans and associated to symptoms and deficits observed in Rett syndrome patients thus providing the first evidence that zebrafish could be an alternative model to study the molecular pathways of this disease as well as to test possible therapeutic approaches capable of rescuing the phenotype.

Altered gut microbiota in Rett syndrome.

PubMed

Strati, Francesco; Cavalieri, Duccio; Albanese, Davide; De Felice, Claudio; Donati, Claudio; Hayek, Joussef; Jousson, Olivier; Leoncini, Silvia; Pindo, Massimo; Renzi, Daniela; Rizzetto, Lisa; Stefanini, Irene; Calabrò, Antonio; De Filippo, Carlotta

2016-07-30

The human gut microbiota directly affects human health, and its alteration can lead to gastrointestinal abnormalities and inflammation. Rett syndrome (RTT), a progressive neurological disorder mainly caused by mutations in MeCP2 gene, is commonly associated with gastrointestinal dysfunctions and constipation, suggesting a link between RTT's gastrointestinal abnormalities and the gut microbiota. The aim of this study was to evaluate the bacterial and fungal gut microbiota in a cohort of RTT subjects integrating clinical, metabolomics and metagenomics data to understand if changes in the gut microbiota of RTT subjects could be associated with gastrointestinal abnormalities and inflammatory status. Our findings revealed the occurrence of an intestinal sub-inflammatory status in RTT subjects as measured by the elevated values of faecal calprotectin and erythrocyte sedimentation rate. We showed that, overall, RTT subjects harbour bacterial and fungal microbiota altered in terms of relative abundances from those of healthy controls, with a reduced microbial richness and dominated by microbial taxa belonging to Bifidobacterium, several Clostridia (among which Anaerostipes, Clostridium XIVa, Clostridium XIVb) as well as Erysipelotrichaceae, Actinomyces, Lactobacillus, Enterococcus, Eggerthella, Escherichia/Shigella and the fungal genus Candida. We further observed that alterations of the gut microbiota do not depend on the constipation status of RTT subjects and that this dysbiotic microbiota produced altered short chain fatty acids profiles. We demonstrated for the first time that RTT is associated with a dysbiosis of both the bacterial and fungal component of the gut microbiota, suggesting that impairments of MeCP2 functioning favour the establishment of a microbial community adapted to the costive gastrointestinal niche of RTT subjects. The altered production of short chain fatty acids associated with this microbiota might reinforce the constipation status of RTT

Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders

USDA-ARS?s Scientific Manuscript database

Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-functi...

Clinical and molecular characterization of females affected by X-linked retinoschisis.

PubMed

Staffieri, Sandra E; Rose, Loreto; Chang, Andrew; De Roach, John N; McLaren, Terri L; Mackey, David A; Hewitt, Alex W; Lamey, Tina M

2015-01-01

X-linked retinoschisis (XLRS) is a leading cause of juvenile macular degeneration associated with mutations in the RS1 gene. XLRS has a variable expressivity in males and shows no clinical phenotype in carrier females. Clinical and molecular characterization of male and female individuals affected with XLRS in a consanguineous family. Consanguineous Eastern European-Australian family Four clinically affected and nine unaffected family members were genetically and clinically characterized. Deoxyribonucleic acid (DNA) analysis was conducted by the Australian Inherited Retinal Disease Register and DNA Bank. Clinical and molecular characterization of the causative mutation in a consanguineous family with XLRS. By direct sequencing of the RS1 gene, one pathogenic variant, NM_000330.3: c.304C > T, p. R102W, was identified in all clinically diagnosed individuals analysed. The two females were homozygous for the variant, and the males were hemizygous. Clinical and genetic characterization of affected homozygous females in XLRS affords the rare opportunity to explore the molecular mechanisms of XLRS and the manifestation of these mutations as disease in humans. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

Psychological Well-Being of Mothers and Siblings in Families of Girls and Women with Rett Syndrome

ERIC Educational Resources Information Center

Cianfaglione, Rina; Hastings, Richard P.; Felce, David; Clarke, Angus; Kerr, Michael P.

2015-01-01

Few published studies have reported on the psychological well-being of family members of individuals with Rett syndrome (RTT). Eighty-seven mothers of girls and women with RTT completed a questionnaire survey about their daughters' behavioral phenotype, current health, and behavior problems, and their own and a sibling's well-being. Mothers…

Norrie disease and exudative vitreoretinopathy in families with affected female carriers.

PubMed

Shastry, B S; Hiraoka, M; Trese, D C; Trese, M T

1999-01-01

Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness, which is often associated with sensorineural hearing loss and mental retardation. X-linked familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina and is not associated with systemic diseases. X-linked recessive disorders generally do not affect females. Here we show that female carriers can be associated with manifestation of an X-linked disorder. A four-generation family with an affected female, and a history of congenital blindness and hearing loss, was identified through the pro-band. A second family, with a full-term female infant, was evaluated through ophthalmic examinations and found to exhibit ocular features, such as retinal folds, retinal detachment and peripheral exudates. Peripheral blood specimens were collected from several affected and unaffected family members. DNA was extracted and analyzed by single-strand conformation polymorphism (SSCP) following polymerase chain reaction (PCR) amplification of the exons of the Norrie disease gene. The amplified products were sequenced by the dideoxy chain termination method. In an X-linked four-generation family, a novel missense (A118D) mutation in the third exon of the Norrie disease gene, was identified. The mutation was transmitted through three generations and cosegregated with the disease. The affected maternal grandmother and the unaffected mother carried the same mutation in one of their alleles. In an unrelated sporadic family, a heterozygous missense mutation (C96Y) was identified in the third exon of the Norrie disease gene in an affected individual. Analysis of exon-1 and 2 of the Norrie disease gene did not reveal any additional sequence alterations in these families. The mutations were not detected in the unaffected family members and the 116 normal unrelated controls, suggesting that they are likely to be the pathogenic mutations

Tyr120Asp mutation alters domain flexibility and dynamics of MeCP2 DNA binding domain leading to impaired DNA interaction: Atomistic characterization of a Rett syndrome causing mutation.

PubMed

D'Annessa, Ilda; Gandaglia, Anna; Brivio, Elena; Stefanelli, Gilda; Frasca, Angelisa; Landsberger, Nicoletta; Di Marino, Daniele

2018-05-01

Mutations in the X-linked MECP2 gene represent the main origin of Rett syndrome, causing a profound intellectual disability in females. MeCP2 is an epigenetic transcriptional regulator containing two main functional domains: a methyl-CpG binding domain (MBD) and a transcription repression domain (TRD). Over 600 pathogenic mutations were reported to affect the whole protein; almost half of missense mutations affect the MBD. Understanding the impact of these mutations on the MBD structure and interaction with DNA will foster the comprehension of their pathogenicity and possibly genotype/phenotype correlation studies. Herein, we use molecular dynamics simulations to obtain a detailed view of the dynamics of WT and mutated MBD in the presence and absence of DNA. The pathogenic mutation Y120D is used as paradigm for our studies. Further, since the Y120 residue was previously found to be a phosphorylation site, we characterize the dynamic profile of the MBD also in the presence of Y120 phosphorylation (pY120). We found that addition of a phosphate group to Y120 or mutation in aspartic acid affect domain mobility that samples an alternative conformational space with respect to the WT, leading to impaired ability to interact with DNA. Experimental assays showing a significant reduction in the binding affinity between the mutated MBD and the DNA confirmed our predictions. Copyright © 2018 Elsevier B.V. All rights reserved.

Choline Ameliorates Disease Phenotypes in Human iPSC Models of Rett Syndrome.

PubMed

Chin, Eunice W M; Marcy, Guillaume; Yoon, Su-In; Ma, Dongliang; Rosales, Francisco J; Augustine, George J; Goh, Eyleen L K

2016-09-01

Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene account for approximately 95 % of all RTT cases. To model RTT in vitro, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of two RTT patients with different mutations (MECP2 (R306C) and MECP2 (1155Δ32)) in their MECP2 gene. We found that these iPSCs were capable of differentiating into functional neurons. Compared to control neurons, the RTT iPSC-derived cells had reduced soma size and a decreased amount of synaptic input, evident both as fewer Synapsin 1-positive puncta and a lower frequency of spontaneous excitatory postsynaptic currents. Supplementation of the culture media with choline rescued all of these defects. Choline supplementation may act through changes in the expression of choline acetyltransferase, an important enzyme in cholinergic signaling, and also through alterations in the lipid metabolite profiles of the RTT neurons. Our study elucidates the possible mechanistic pathways for the effect of choline on human RTT cell models, thereby illustrating the potential for using choline as a nutraceutical to treat RTT.

The utility of Next Generation Sequencing for molecular diagnostics in Rett syndrome.

PubMed

Vidal, Silvia; Brandi, Núria; Pacheco, Paola; Gerotina, Edgar; Blasco, Laura; Trotta, Jean-Rémi; Derdak, Sophia; Del Mar O'Callaghan, Maria; Garcia-Cazorla, Àngels; Pineda, Mercè; Armstrong, Judith

2017-09-25

Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that almost exclusively affects girls and is totally disabling. Three genes have been identified that cause RTT: MECP2, CDKL5 and FOXG1. However, the etiology of some of RTT patients still remains unknown. Recently, next generation sequencing (NGS) has promoted genetic diagnoses because of the quickness and affordability of the method. To evaluate the usefulness of NGS in genetic diagnosis, we present the genetic study of RTT-like patients using different techniques based on this technology. We studied 1577 patients with RTT-like clinical diagnoses and reviewed patients who were previously studied and thought to have RTT genes by Sanger sequencing. Genetically, 477 of 1577 patients with a RTT-like suspicion have been diagnosed. Positive results were found in 30% by Sanger sequencing, 23% with a custom panel, 24% with a commercial panel and 32% with whole exome sequencing. A genetic study using NGS allows the study of a larger number of genes associated with RTT-like symptoms simultaneously, providing genetic study of a wider group of patients as well as significantly reducing the response time and cost of the study.

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations.

PubMed

Hadzsiev, Kinga; Polgar, Noemi; Bene, Judit; Komlosi, Katalin; Karteszi, Judit; Hollody, Katalin; Kosztolanyi, Gyorgy; Renieri, Alessandra; Melegh, Bela

2011-03-01

Rett syndrome (RTT) is characterized by a relatively specific clinical phenotype. We screened 152 individuals with RTT phenotype. A total of 22 different known MECP2 mutations were identified in 42 subjects (27.6%). Of the 22 mutations, we identified 7 (31.8%) frameshift-causing deletions, 4 (18.2%) nonsense, 10 (45.5%) missense mutations and one insertion (4.5%). The most frequent pathologic changes were: p.Thr158Met (14.2%) and p.Arg133Cys (11.9%) missense, and p.Arg255Stop (9.5%) and p.Arg294Stop (9.5%) nonsense mutations. We also detected the c.925C >T (p.Arg309Trp) mutation in an affected patient, whose role in RTT pathogenesis is still unknown. Patients without detectable MECP2 defects were screened for mutations of cyclin-dependent kinase-like 5 (CDKL5) gene, responsible for the early-onset variant of RTT. We discovered two novel mutations: c.607G >T resulting in a termination codon at aa203, disrupting the catalytic domain, and c.1708G >T leading to a stop at aa570 of the C terminus. Both patients with CDKL5 mutation presented therapy-resistant epilepsy and a phenotype fitting with the diagnosis of early-onset variant of RTT. No FOXG1 mutation was detected in any of the remaining patients. A total of 110 (72.5%) patients remained without molecular genetic diagnosis that necessitates further search for novel gene mutations in this phenotype. Our results also suggest the need of screening for CDKL5 mutations in patients with Rett phenotype tested negative for MECP2 mutations.

Management of a severe forceful breather with Rett syndrome using carbogen.

PubMed

Smeets, Eric E J; Julu, Peter O O; van Waardenburg, Dick; Engerström, Ingegerd Witt; Hansen, Stig; Apartopoulos, Flora; Curfs, Leopold M G; Schrander-Stumpel, Connie T R M

2006-11-01

We have used a novel neurophysiological technique in the NeuroScope system in combination with conventional electroencephalography (EEG) to monitor both brainstem and cortical activity simultaneously in real-time in a girl with Rett syndrome. The presenting clinical features in our patient were severe sleep disturbances, irregular breathing in the awake state dominated by Valsalva's type of breathing followed by tachypnoea and very frequent attacks of seizures and vacant spells. Our novel neurophysiological data showed that the patient was a Forceful Breather according to the breathing categories in Rett syndrome. She had frequent abnormal spontaneous brainstem activation (ASBA) preceded by severe attacks of hypocapnoea, which was caused by a combination of Valsalva's type of breathing and tachypnoea and all these together were responsible for the seizures and non-epileptic vacant spells. The ASBA was not detectable in conventional EEG and there were no epileptiform changes in the EEG during the seizures and vacant spells caused by the hypocapnic attacks, therefore these were pseudo-seizures. The record of brainstem activity confirmed that these were autonomic events, a kind of "brainstem epilepsy". We successfully treated the sleep disturbance with Pipamperone, a 5-hydroxytryptophan antagonist of receptor type 2 and we prevented the severe hypocapnoea during Valsalva's type of breathing and during tachypnoea using carbogen (a mixture of 5% carbon dioxide and 95% oxygen), which we gave by inhalation. Our treatment drastically reduced the autonomic events, promoted whole night sleep and significantly improved the quality of life in our patient. She can now participate in normal family activity which was previously impossible before treatment.

Improvement in motor and exploratory behavior in Rett syndrome mice with restricted ketogenic and standard diets.

PubMed

Mantis, John G; Fritz, Christie L; Marsh, Jeremy; Heinrichs, Stephen C; Seyfried, Thomas N

2009-06-01

Rett syndrome (RTT) is a rare X-linked autistic-spectrum neurological disorder associated with impaired energy metabolism, seizure susceptibility, progressive social behavioral regression, and motor impairment primarily in young girls. The objective of this study was to examine the influence of restricted diets, including a ketogenic diet (KD) and a standard rodent chow diet (SD), on behavior in male Mecp2(308/y) mice, a model of RTT. The KD is a high-fat, low-carbohydrate diet that has anticonvulsant efficacy in children with intractable epilepsy and may be therapeutic in children with RTT. Following an 11-day pretrial period, adult wild-type and mutant Rett mice were separated into groups that were fed either an SD in unrestricted or restricted amounts or a ketogenic diet (KetoCal) in restricted amounts for a total of 30 days. The restricted diets were administered to reduce mouse body weight by 20-23% compared to the body weight of each mouse before the initiation of the diet. All mice were subjected to a battery of behavioral tests to determine the influence of the diet on the RTT phenotype. We found that performance in tests of motor behavior and anxiety was significantly worse in male RTT mice compared to wild-type mice and that restriction of either the KD or the SD improved motor behavior and reduced anxiety. We conclude that although both restricted diets increased the tendency of Rett mice to explore a novel environment, the beneficial effects of the KD were due more to calorie restriction than to the composition of the diet. Our findings suggest that calorically restricted diets could be effective in reducing the anxiety and in improving motor behavior in girls with RTT.

Does microglial dysfunction play a role in autism and Rett syndrome?

PubMed Central

MAEZAWA, IZUMI; CALAFIORE, MARCO; WULFF, HEIKE; JIN, LEE-WAY

2016-01-01

Autism spectrum disorders (ASDs) including classic autism is a group of complex developmental disabilities with core deficits of impaired social interactions, communication difficulties and repetitive behaviors. Although the neurobiology of ASDs has attracted much attention in the last two decades, the role of microglia has been ignored. Existing data are focused on their recognized role in neuroinflammation, which only covers a small part of the pathological repertoire of microglia. This review highlights recent findings on the broader roles of microglia, including their active surveillance of brain microenvironments and regulation of synaptic connectivity, maturation of brain circuitry and neurogenesis. Emerging evidence suggests that microglia respond to pre- and postnatal environmental stimuli through epigenetic interface to change gene expression, thus acting as effectors of experience-dependent synaptic plasticity. Impairments of these microglial functions could substantially contribute to several major etiological factors of autism, such as environmental toxins and cortical underconnectivity. Our recent study on Rett syndrome, a syndromic autistic disorder, provides an example that intrinsic microglial dysfunction due to genetic and epigenetic aberrations could detrimentally affect the developmental trajectory without evoking neuroinflammation. We propose that ASDs provide excellent opportunities to study the influence of microglia on neurodevelopment, and this knowledge could lead to novel therapies. PMID:22717189

Placebo-controlled crossover assessment of mecasermin for the treatment of Rett syndrome.

PubMed

O'Leary, Heather M; Kaufmann, Walter E; Barnes, Katherine V; Rakesh, Kshitiz; Kapur, Kush; Tarquinio, Daniel C; Cantwell, Nicole G; Roche, Katherine J; Rose, Suzanne A; Walco, Alexandra C; Bruck, Natalie M; Bazin, Grace A; Holm, Ingrid A; Alexander, Mark E; Swanson, Lindsay C; Baczewski, Lauren M; Mayor Torres, Juan M; Nelson, Charles A; Sahin, Mustafa

2018-03-01

To measure the efficacy of mecasermin (recombinant human insulin-like growth factor 1, rhIGF-1), for treating symptoms of Rett syndrome (RTT) in a pediatric population using a double-blind crossover study design. Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rhIGF-1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28-week washout period. The primary endpoints were as follows: Anxiety Depression and Mood Scale (ADAMS) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire (RSBQ) Fear/Anxiety subscale, Parent Target Symptom Visual Analog Scale (PTSVAS) top three concerns, Clinical Global Impression (CGI), Parent Global Impression (PGI), and the Kerr severity scale. Cardiorespiratory- and electroencephalography (EEG)-based biomarkers were also analyzed. There were no significant differences between randomization groups. The majority of AEs were mild to moderate, although 12 episodes of serious AEs occurred. The Kerr severity scale, ADAMS Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography (EEG) parameters also deteriorated. A secondary analysis of subjects who were not involved in a placebo recall confirmed most of these findings. However, it also revealed improvements on a measure of stereotypic behavior and another of social communication. As in the phase 1 trial, rhIGF-1 was safe; however, the drug did not reveal significant improvement, and some parameters worsened.

[Epigenome: what we learned from Rett syndrome, a neurological disease caused by mutation of a methyl-CpG binding protein].

PubMed

Kubota, Takeo

2013-01-01

Epigenome is defined as DNA and histone modification-dependent gene regulation system. Abnormalities in this system are known to cause various neuro-developmental diseases. We recently reported that neurological symptoms of Rett syndrome, which is an autistic disorder caused by mutations in methyl-CpG binding protein 2 (MeCP2), was associated with failure of epigenomic gene regulation in neuronal cells, and that clinical differences in the identical twins with Rett syndrome in the differences in DNA methylation in neuronal genes, but not caused by DNA sequence differences. Since central nervus system requires precise gene regulation, neurological diseases including Alzheimer and Parkinson diseases may be caused by acquired DNA modification (epigenomic) changes that results in aberrant gene regulation as well as DNA sequence changes congenitally occurred (mutation).

Identification of novel genetic causes of Rett syndrome-like phenotypes.

PubMed

Lopes, Fátima; Barbosa, Mafalda; Ameur, Adam; Soares, Gabriela; de Sá, Joaquim; Dias, Ana Isabel; Oliveira, Guiomar; Cabral, Pedro; Temudo, Teresa; Calado, Eulália; Cruz, Isabel Fineza; Vieira, José Pedro; Oliveira, Renata; Esteves, Sofia; Sauer, Sascha; Jonasson, Inger; Syvänen, Ann-Christine; Gyllensten, Ulf; Pinto, Dalila; Maciel, Patrícia

2016-03-01

The aim of this work was to identify new genetic causes of Rett-like phenotypes using array comparative genomic hybridisation and a whole exome sequencing approach. We studied a cohort of 19 Portuguese patients (16 girls, 3 boys) with a clinical presentation significantly overlapping Rett syndrome (RTT). Genetic analysis included filtering of the single nucleotide variants and indels with preference for de novo, homozygous/compound heterozygous, or maternally inherited X linked variants. Examination by MRI and muscle biopsies was also performed. Pathogenic genomic imbalances were found in two patients (10.5%): an 18q21.2 deletion encompassing four exons of the TCF4 gene and a mosaic UPD of chromosome 3. Variants in genes previously implicated in neurodevelopmental disorders (NDD) were identified in six patients (32%): de novo variants in EEF1A2, STXBP1 and ZNF238 were found in three patients, maternally inherited X linked variants in SLC35A2, ZFX and SHROOM4 were detected in two male patients and one homozygous variant in EIF2B2 was detected in one patient. Variants were also detected in five novel NDD candidate genes (26%): we identified de novo variants in the RHOBTB2, SMARCA1 and GABBR2 genes; a homozygous variant in EIF4G1; compound heterozygous variant in HTT. Network analysis reveals that these genes interact by means of protein interactions with each other and with the known RTT genes. These findings expand the phenotypical spectrum of previously known NDD genes to encompass RTT-like clinical presentations and identify new candidate genes for RTT-like phenotypes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Neurophysiological responses to music and vibroacoustic stimuli in Rett syndrome.

PubMed

Bergström-Isacsson, Märith; Lagerkvist, Bengt; Holck, Ulla; Gold, Christian

2014-06-01

People with Rett syndrome (RTT) have severe communicative difficulties. They have as well an immature brainstem that implies dysfunction of the autonomic nervous system. Music plays an important role in their life, is often used as a motivating tool in a variety of situations and activities, and caregivers are often clear about people with RTTs favourites. The aim of this study was to investigate physiological and emotional responses related to six different musical stimuli in people with RTT. The study included 29 participants with RTT who were referred to the Swedish Rett Center for medical brainstem assessment during the period 2006-2007. 11 children with a typical developmental pattern were used as comparison. A repeated measures design was used, and physiological data were collected from a neurophysiological brainstem assessment. The continuous dependent variables measured were Cardiac Vagal Tone (CVT), Cardiac Sensitivity to Baroreflex (CSB), Mean Arterial Blood Pressure (MAP) and the Coefficient of Variation of Mean Arterial Blood Pressure (MAP-CV). These parameters were used to categorise brainstem responses as parasympathetic (calming) response, sympathetic (activating) response, arousal (alerting) response and unclear response. The results showed that all participants responded to the musical stimuli, but not always in the expected way. It was noticeable that both people with and without RTT responded with an arousal to all musical stimuli to begin with. Even though the initial expressions sometimes changed after some time due to poor control functions of their brainstem, the present results are consistent with the possibility that the RTT participants' normal responses to music are intact. These findings may explain why music is so important for individuals with RTT throughout life. Copyright © 2014 Elsevier Ltd. All rights reserved.

Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome.

PubMed

Moretti, Paolo; Bouwknecht, J Adriaan; Teague, Ryan; Paylor, Richard; Zoghbi, Huda Y

2005-01-15

Rett syndrome (RTT) is an autistic spectrum disorder with a known genetic basis. RTT is caused by loss of function mutations in the X-linked gene MECP2 and is characterized by loss of acquired motor, social and language skills in females beginning at 6-18 months of age. MECP2 mutations also cause non-syndromic mental retardation in males and females, and abnormalities of MeCP2 expression in the brain have been found in autistic spectrum disorders. We studied home-cage behavior and social interactions in a mouse model of RTT (Mecp2(308/Y)) carrying a mutation similar to common RTT causing alleles. Young adult mutant mice showed abnormal home-cage diurnal activity in the absence of motor skill deficits. Nesting, a phenotype related to social behavior, and social interactions were both impaired in these animals. Mecp2(308/Y) mice showed deficits in nest building and decreased nest use. Although there were no differences in aggression or exploration of novel inanimate stimuli, mutant mice took less initiative and were less decisive approaching unfamiliar males and spent less time in close vicinity to them in several social interaction paradigms. The abnormalities of diurnal activity and social behavior in Mecp2(308/Y) mice are reminiscent of the sleep/wake dysfunction and autistic features of RTT. These data suggest that MECP2 regulates the expression and/or function of genes involved in social behavior. The study of Mecp2(308/Y) mice will allow the identification of the molecular basis of social impairment in RTT and related autistic spectrum disorders.

The short-time structural plasticity of dendritic spines is altered in a model of Rett syndrome.

PubMed

Landi, Silvia; Putignano, Elena; Boggio, Elena Maria; Giustetto, Maurizio; Pizzorusso, Tommaso; Ratto, Gian Michele

2011-01-01

The maturation of excitatory transmission comes about through a developmental period in which dendritic spines are highly motile and their number, form and size are rapidly changing. Surprisingly, although these processes are crucial for the formation of cortical circuitry, little is known about possible alterations of these processes in brain disease. By means of acute in vivo 2-photon imaging we show that the dynamic properties of dendritic spines of layer V cortical neurons are deeply affected in a mouse model of Rett syndrome (RTT) at a time around P25 when the neuronal phenotype of the disease is still mild. Then, we show that 24h after a subcutaneous injection of IGF-1 spine dynamics is restored. Our study demonstrates that spine dynamics in RTT mice is severely impaired early during development and suggest that treatments for RTT should be started very early in order to reestablish a normal period of spine plasticity.

How Facial Expressions in a Rett Syndrome Population Are Recognised and Interpreted by Those around Them as Conveying Emotions

ERIC Educational Resources Information Center

Bergstrom-Isacsson, Marith; Lagerkvist, Bengt; Holck, Ulla; Gold, Christian

2013-01-01

Rett syndrome (RTT) is a neurodevelopmental disorder, including autonomic nervous system dysfunctions and severe communication impairment with an extremely limited ability to use verbal language. These individuals are therefore dependent on the capacity of caregivers to observe and interpret communicative signals, including emotional expressions.…

Adapting the Mullen Scales of Early Learning for a Standardized Measure of Development in Children with Rett Syndrome

ERIC Educational Resources Information Center

Clarkson, Tessa; LeBlanc, Jocelyn; DeGregorio, Geneva; Vogel-Farley, Vanessa; Barnes, Katherine; Kaufmann, Walter E.; Nelson, Charles A.

2017-01-01

Rett Syndrome (RTT) is characterized by severe impairment in fine motor (FM) and expressive language (EL) function, making accurate evaluations of development difficult with standardized assessments. In this study, the administration and scoring of the Mullen Scales of Early Learning (MSEL) were adapted to eliminate the confounding effects of FM…

Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms.

PubMed

Zahorakova, Daniela; Rosipal, Robert; Hadac, Jan; Zumrova, Alena; Bzduch, Vladimir; Misovicova, Nadezda; Baxova, Alice; Zeman, Jiri; Martasek, Pavel

2007-01-01

Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder in females, is caused mainly by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Here we report mutation analysis of the MECP2 gene in 87 patients with RTT from the Czech and Slovak Republics, and Ukraine. The patients, all girls, with classical RTT were investigated for mutations using bi-directional DNA sequencing and conformation sensitive gel electrophoresis analysis of the coding sequence and exon/intron boundaries of the MECP2 gene. Restriction fragment length polymorphism analysis was performed to confirm the mutations that cause the creation or abolition of the restriction site. Mutation-negative cases were subsequently examined by multiple ligation-dependent probe amplification (MLPA) to identify large deletions. Mutation screening revealed 31 different mutations in 68 patients and 12 non-pathogenic polymorphisms. Six mutations have not been previously published: two point mutations (323T>A, 904C>T), three deletions (189_190delGA, 816_832del17, 1069delAGC) and one deletion/inversion (1063_1236del174;1189_1231inv43). MLPA analysis revealed large deletions in two patients. The detection rate was 78.16%. Our results confirm the high frequency of MECP2 mutations in females with RTT and provide data concerning the mutation heterogeneity in the Slavic population.

[Analysis of the parental origin of MECP2 mutations in patients with Rett syndrome].

PubMed

Zhang, Jing-jing; Bao, Xin-hua; Cao, Guang-na; Jiang, Sheng-ling; Zhu, Xing-wang; Lu, Hong-mei; Jia, Li-fang; Pan, Hong; Wu, Xi-ru

2010-04-01

To identify the parental origin of methyl-CpG-binding protein 2 (MECP2) gene mutations in Chinese patients with Rett syndrome. Single nucleotide polymorphisms (SNPs) in intron 3 of the MECP2 gene were analyzed by PCR and sequencing in 115 patients with Rett syndrome. Then sequencing of the SNP region was performed for the fathers of the patients who had at least one SNP, to determine which allele was from the father. Then allele-specific PCR was performed and the products were sequenced to see whether the allele from father or mother harbored the mutation. Seventy-six of the 115 patients had at least one SNP. Three hot SNPs were found in these patients. They were: IVS3+22C >G, IVS3+266C >T and IVS3+683C>T. Among the 76 cases, 73 had a paternal origin of MECP2 mutations, and the other 3 had a maternal origin. There were multiple types of MECP2 mutation of the paternal origin, including 4 frame shift, 2 deletion and 67 point (56C >T, 6C >G, 2A >G, 2G >T and 1A >T) mutations. The mutation types of the 3 patients with maternal origin included 2 frame shift and 1 point (C >T) mutation. In Chinese RTT patients, the MECP2 mutations are mostly of paternal origin.

Hand stereotypies distinguish Rett syndrome from autism disorder.

PubMed

Goldman, Sylvie; Temudo, Teresa

2012-07-01

Rett syndrome (RTT) and autism disorder (AD) are 2 neurodevelopmental disorders of early life that share phenotypic features, one being hand stereotypies. Distinguishing RTT from AD often represents a challenge, and given their distinct long-term prognoses, this issue may have far-reaching implications. With the advances in genetic testing, the contribution of clinical manifestations in distinguishing RTT from AD has been overlooked. A comparison of hand stereotypies in 20 children with RTT and 20 with AD was performed using detailed analyses of videotaped standardized observations. Striking differences are observed between RTT and AD children. In RTT, hand stereotypies are predominantly complex, continuous, localized to the body midline, and involving mouthing. Conversely, in AD children, hand stereotypies are simple, bilateral, intermittent, and often involving objects. These results provide important clinical signs useful to the differential diagnosis of RTT versus AD, especially when genetic testing for RTT is not an option. Copyright © 2012 Movement Disorder Society.

A role for metabolism in Rett syndrome pathogenesis

PubMed Central

Justice, Monica J; Buchovecky, Christie M; Kyle, Stephanie M; Djukic, Aleksandra

2013-01-01

Rett syndrome (RTT), an X-linked neurological disorder caused by mutations in MECP2, may have a metabolic component. We reported a genetic suppressor screen in a Mecp2-null mouse model to identify pathways for therapeutic improvement of RTT symptoms. Of note, one suppressor mutation implied that cholesterol homeostasis was perturbed in Mecp2 null mice; indeed, cholesterol synthesis was elevated in the brain and body system. Remarkably, the genetic effect of downregulating the cholesterol pathway could be mimicked chemically by statin drugs, improving motor symptoms, and increasing longevity in the mouse. Our work linked cholesterol metabolism to RTT pathology for the first time. Both neurological and systemic effects of perturbed cholesterol homeostasis overlap with many RTT symptoms. Here we show in patients that peripheral cholesterol, triglycerides, and/or LDLs may be elevated early in RTT disease onset, providing a biomarker for patients that could be aided by therapeutic interventions that modulate lipid metabolism. PMID:25003017

The Contribution of Qualitative Research Towards the Issues Affecting Female Undergraduate Engineering Students

ERIC Educational Resources Information Center

Duggan, Louise Maria

2015-01-01

This article explores the use of qualitative research methods towards our understanding of the issues affecting female undergraduate engineers. As outlined in this article female engineering students face many challenges during their undergraduate studies. Qualitative research methods provide an opportunity to gain a deeper understanding of the…

Increased Mitochondrial Mass and Cytosolic Redox Imbalance in Hippocampal Astrocytes of a Mouse Model of Rett Syndrome: Subcellular Changes Revealed by Ratiometric Imaging of JC-1 and roGFP1 Fluorescence

PubMed Central

Bebensee, Dörthe F.

2017-01-01

Rett syndrome (RTT) is a neurodevelopmental disorder with mutations in the MECP2 gene. Mostly girls are affected, and an apparently normal development is followed by cognitive impairment, motor dysfunction, epilepsy, and irregular breathing. Various indications suggest mitochondrial dysfunction. In Rett mice, brain ATP levels are reduced, mitochondria are leaking protons, and respiratory complexes are dysregulated. Furthermore, we found in MeCP2-deficient mouse (Mecp2−/y) hippocampus an intensified mitochondrial metabolism and ROS generation. We now used emission ratiometric 2-photon imaging to assess mitochondrial morphology, mass, and membrane potential (ΔΨm) in Mecp2−/y hippocampal astrocytes. Cultured astrocytes were labeled with the ΔΨm marker JC-1, and semiautomated analyses yielded the number of mitochondria per cell, their morphology, and ΔΨm. Mecp2−/y astrocytes contained more mitochondria than wild-type (WT) cells and were more oxidized. Mitochondrial size, ΔΨm, and vulnerability to pharmacological challenge did not differ. The antioxidant Trolox opposed the oxidative burden and decreased the mitochondrial mass, thereby dampening the differences among WT and Mecp2−/y astrocytes; mitochondrial size and ΔΨm were not markedly affected. In conclusion, mitochondrial alterations and redox imbalance in RTT also involve astrocytes. Mitochondria are more numerous in Mecp2−/y than in WT astrocytes. As this genotypic difference is abolished by Trolox, it seems linked to the oxidative stress in RTT. PMID:28894505

Male irradiation affects female remating behavior in Anastrepha serpentina (Diptera: Tephritidae).

PubMed

Landeta-Escamilla, Anais; Hernández, Emilio; Arredondo, José; Díaz-Fleischer, Francisco; Pérez-Staples, Diana

2016-02-01

Female remating in target pest species can affect the efficacy of control methods such as the Sterile Insect Technique (SIT) but very little is known about the postcopulatory mating behavior of these pests. In this study, we investigated the remating behavior of female Anastrepha serpentina (Diptera: Tephritidae), an oligophagous pest of Sapotaceae. First, we tested how long the sexual refractory period of females lasted after an initial mating. Second, we tested the effect of male and female sterility, female ovipositing opportunities and male density on female propensity to remate. Lastly, we tested if the amount of sperm stored by females was correlated to the likelihood of females to remate. We found that receptivity of mass-reared A. serpentina females had a bimodal response, with up to 16% of mass-reared A. serpentina females remating five days after the initial copulation, decreasing to 2% at 10 and 15 days and increasing to 13% after 20 days. Compared to fertile males, sterile males were less likely to mate and less likely to inhibit females from remating. Copula duration of sterile males was shorter compared to fertile males. Remating females were less likely to mate with a sterile male as a second mate. Sterile females were less likely to mate or remate compared to fertile females. Opportunity to oviposit and male density had no effect on female remating probability. Sperm numbers were not correlated with female likelihood to remate. Information on the post-copulatory behavior of mass-reared A. serpentina will aid fruit fly managers in improving the quality of sterile males. We discuss our results in terms of the differences this species presents in female remating behavior compared to other tephritids. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biomechanical properties of bone in a mouse model of Rett syndrome.

PubMed

Kamal, Bushra; Russell, David; Payne, Anthony; Constante, Diogo; Tanner, K Elizabeth; Isaksson, Hanna; Mathavan, Neashan; Cobb, Stuart R

2015-02-01

Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (MECP2) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, MECP2 is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous Mecp2(stop/y) male mice in which Mecp2 is silenced in all cells and female Mecp2(stop/+) mice in which Mecp2 is silenced in ~50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of Mecp2 in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies. Copyright © 2014. Published by Elsevier Inc.

Biomechanical properties of bone in a mouse model of Rett syndrome

PubMed Central

Kamal, Bushra; Russell, David; Payne, Anthony; Constante, Diogo; Tanner, K. Elizabeth; Isaksson, Hanna; Mathavan, Neashan; Cobb, Stuart R.

2015-01-01

Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (MECP2) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, MECP2 is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous Mecp2stop/y male mice in which Mecp2 is silenced in all cells and female Mecp2stop/+ mice in which Mecp2 is silenced in ~ 50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of Mecp2 in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies. PMID:25445449

Developmental profile of speech-language and communicative functions in an individual with the preserved speech variant of Rett syndrome.

PubMed

Marschik, Peter B; Vollmann, Ralf; Bartl-Pokorny, Katrin D; Green, Vanessa A; van der Meer, Larah; Wolin, Thomas; Einspieler, Christa

2014-08-01

We assessed various aspects of speech-language and communicative functions of an individual with the preserved speech variant of Rett syndrome (RTT) to describe her developmental profile over a period of 11 years. For this study, we incorporated the following data resources and methods to assess speech-language and communicative functions during pre-, peri- and post-regressional development: retrospective video analyses, medical history data, parental checklists and diaries, standardized tests on vocabulary and grammar, spontaneous speech samples and picture stories to elicit narrative competences. Despite achieving speech-language milestones, atypical behaviours were present at all times. We observed a unique developmental speech-language trajectory (including the RTT typical regression) affecting all linguistic and socio-communicative sub-domains in the receptive as well as the expressive modality. Future research should take into consideration a potentially considerable discordance between formal and functional language use by interpreting communicative acts on a more cautionary note.

Social-emotional instability in individuals with Rett syndrome: parents' experiences with second stage behaviour.

PubMed

Munde, V; Vlaskamp, C; Ter Haar, A

2016-01-01

While the medical profession often terms behaviours in individuals with Rett syndrome (RTT) in the second stage as 'autistic-like', parents disagree with this description. The present study focuses on a comparison of parents' experiences with the social-emotional behaviour of the child with RTT in the second and subsequent stages. In collaboration with the Dutch Rett Syndrome Organization, 51 parents of children with RTT in the Netherlands took part in the present study. Parents completed an online questionnaire to clarify their experiences of the social-emotional behaviour of their children during and after the second stage of RTT. Both quantitative and qualitative analysis techniques have been used. The results of the paired-samples t-test show that parents see significantly less social-emotional behaviour in the children during the second stage of RTT than in the subsequent stages. Parents reported that their children did not seek as much interaction. From the parents' descriptions, it would seem that the children are willing but unable to interact with their environment. Like previous research, our study leads to doubts about the appropriateness of the label 'autistic-like' for the behaviour of individuals in the second stage of RTT. While behaviours of individuals with autism and individuals with RTT may resemble each other, quality and intentions may differ. Still, future studies are needed for further clarification. © 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Distinguishing response to names in Rett and MECP2 Duplication syndrome: An ERP study of auditory social information processing.

PubMed

Peters, Sarika U; Katzenstein, Ashley; Jones, Dorita; Key, Alexandra P

2017-11-15

Despite significant advances at the level of basic research, the characterization of higher-level processes in Rett and MECP2 Duplication syndrome remains understudied. In this pilot study, we assessed social-emotional information processing by testing whether children (ages 4-12years) with Rett (n=9) and MECP2 Duplication syndrome (n=7) distinguished their own spoken name from other names. We hypothesized that own and familiar names would elicit more positive parietal P300 responses than unknown names, and that the groups would have different neural responses to these stimuli. The MECP2 Duplication group partially mirrored the parietal responses to own name observed in typically developing participants, and better name discrimination correlated with more adaptive behaviors. Conversely, participants with RTT did not resemble the typical group, and showed greater responses to close other names at frontal/central regions. These results may reflect the different consequences of too much (MECP2 Duplication) vs. too little (RTT) MeCP2 protein. Copyright © 2017 Elsevier B.V. All rights reserved.

Misregulation of Alternative Splicing in a Mouse Model of Rett Syndrome

PubMed Central

Li, Ronghui; Dong, Qiping; Yuan, Xinni; Zeng, Xin; Gao, Yu; Li, Hongda; Keles, Sunduz; Wang, Zefeng; Chang, Qiang

2016-01-01

Mutations in the human MECP2 gene cause Rett syndrome (RTT), a severe neurodevelopmental disorder that predominantly affects girls. Despite decades of work, the molecular function of MeCP2 is not fully understood. Here we report a systematic identification of MeCP2-interacting proteins in the mouse brain. In addition to transcription regulators, we found that MeCP2 physically interacts with several modulators of RNA splicing, including LEDGF and DHX9. These interactions are disrupted by RTT causing mutations, suggesting that they may play a role in RTT pathogenesis. Consistent with the idea, deep RNA sequencing revealed misregulation of hundreds of splicing events in the cortex of Mecp2 knockout mice. To reveal the functional consequence of altered RNA splicing due to the loss of MeCP2, we focused on the regulation of the splicing of the flip/flop exon of Gria2 and other AMPAR genes. We found a significant splicing shift in the flip/flop exon toward the flop inclusion, leading to a faster decay in the AMPAR gated current and altered synaptic transmission. In summary, our study identified direct physical interaction between MeCP2 and splicing factors, a novel MeCP2 target gene, and established functional connection between a specific RNA splicing change and synaptic phenotypes in RTT mice. These results not only help our understanding of the molecular function of MeCP2, but also reveal potential drug targets for future therapies. PMID:27352031

Social Context–Induced Song Variation Affects Female Behavior and Gene Expression

PubMed Central

Woolley, Sarah C; Doupe, Allison J

2008-01-01

mesopallium (CMM) was most affected by whether a song was directed or undirected, whereas the caudomedial nidopallium (NCM) was most affected by whether a song was familiar or unfamiliar. Together these data demonstrate that females detect and prefer the features of directed song and suggest that high-level auditory areas including the CMM are involved in this social perception. PMID:18351801

Developmental profile of speech-language and communicative functions in an individual with the Preserved Speech Variant of Rett syndrome

PubMed Central

Marschik, Peter B.; Vollmann, Ralf; Bartl-Pokorny, Katrin D.; Green, Vanessa A.; van der Meer, Larah; Wolin, Thomas; Einspieler, Christa

2018-01-01

Objective We assessed various aspects of speech-language and communicative functions of an individual with the preserved speech variant (PSV) of Rett syndrome (RTT) to describe her developmental profile over a period of 11 years. Methods For this study we incorporated the following data resources and methods to assess speech-language and communicative functions during pre-, peri- and post-regressional development: retrospective video analyses, medical history data, parental checklists and diaries, standardized tests on vocabulary and grammar, spontaneous speech samples, and picture stories to elicit narrative competences. Results Despite achieving speech-language milestones, atypical behaviours were present at all times. We observed a unique developmental speech-language trajectory (including the RTT typical regression) affecting all linguistic and socio-communicative sub-domains in the receptive as well as the expressive modality. Conclusion Future research should take into consideration a potentially considerable discordance between formal and functional language use by interpreting communicative acts on a more cautionary note. PMID:23870013

The course of awake breathing disturbances across the lifespan in Rett syndrome.

PubMed

Tarquinio, Daniel C; Hou, Wei; Neul, Jeffrey L; Berkmen, Gamze Kilic; Drummond, Jana; Aronoff, Elizabeth; Harris, Jennifer; Lane, Jane B; Kaufmann, Walter E; Motil, Kathleen J; Glaze, Daniel G; Skinner, Steven A; Percy, Alan K

2018-04-12

Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2, is associated with a peculiar breathing disturbance exclusively during wakefulness that is distressing, and can even prompt emergency resuscitation. Through the RTT Natural History Study, we characterized cross sectional and longitudinal characteristics of awake breathing abnormalities in RTT and identified associated clinical features. Participants were recruited from 2006 to 2015, and cumulative lifetime prevalence of breathing dysfunction was determined using the Kaplan-Meier estimator. Risk factors were assessed using logistic regression. Of 1205 participants, 1185 had sufficient data for analysis, including 922 females with classic RTT, 778 of whom were followed longitudinally for up to 9.0 years, for a total of 3944 person-years. Participants with classic or atypical severe RTT were more likely to have breathing dysfunction (nearly 100% over the lifespan) compared to those with atypical mild RTT (60-70%). Remission was common, lasting 1 year on average, with 15% ending the study in terminal remission. Factors associated with higher odds of severe breathing dysfunction included poor gross and fine motor function, frequency of stereotypical hand movements, seizure frequency, prolonged corrected QT interval on EKG, and two quality of life metrics: caregiver concern about physical health and contracting illness. Factors associated with lower prevalence of severe breathing dysfunction included higher body mass index and head circumference Z-scores, advanced age, and severe scoliosis or contractures. Awake breathing dysfunction is common in RTT, more so than seizures, and is associated with function, quality of life and risk for cardiac dysrhythmia. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

An Analysis of the Factors Affecting the Career Orientation/Turnover Behavior of Female Naval Officers.

DTIC Science & Technology

1987-12-01

that there are five major, levels of needs in an ascending hierarchy: physiological, safety, social, self - esteem and self actualization. Once a need is...California OI FIlE CMP 0 THESIS AN ANALYSIS OF THE FACTORS AFFECTING THE CAREER ORIENTATION/TURNOVER BEHAVIOR OF FEMALE NAVAL OFFICERS by Richard W. Lowell...PROGRAM PROJECT TASK WORK UNIT ELEMENT NO. NO. No. ACCESSION NO A ,gNcg ecc%rv,.y~ra 1AS AFFECTING THE CAREER ORIENTATION/TURNOVER BEHAVIOR OF FEMALE NAVAL

Sexually transmitted bacteria affect female cloacal assemblages in a wild bird

USGS Publications Warehouse

White, Joël; Mirleau, Pascal; Danchin, Etienne; Mulard, Hervé; Hatch, Scott A.; Heeb, Phillipp; Wagner, Richard H.

2010-01-01

Sexual transmission is an important mode of disease propagation, yet its mechanisms remain largely unknown in wild populations. Birds comprise an important model for studying sexually transmitted microbes because their cloaca provides a potential for both gastrointestinal pathogens and endosymbionts to become incorporated into ejaculates. We experimentally demonstrate in a wild population of kittiwakes (Rissa tridactyla) that bacteria are transmitted during copulation and affect the composition and diversity of female bacterial communities. We used an anti-insemination device attached to males in combination with a molecular technique (automated ribosomal intergenic spacer analysis) that describes bacterial communities. After inseminations were experimentally blocked, the cloacal communities of mates became increasingly dissimilar. Moreover, female cloacal diversity decreased and the extinction of mate-shared bacteria increased, indicating that female cloacal assemblages revert to their pre-copulatory state and that the cloaca comprises a resilient microbial ecosystem.

Daily Rhythmic Behaviors and Thermoregulatory Patterns Are Disrupted in Adult Female MeCP2-Deficient Mice

PubMed Central

Wu, Chiping; Bardakjian, Berj L.; Zhang, Liang; Eubanks, James H.

2012-01-01

Mutations in the X-linked gene encoding Methyl-CpG-binding protein 2 (MECP2) have been associated with neurodevelopmental and neuropsychiatric disorders including Rett Syndrome, X-linked mental retardation syndrome, severe neonatal encephalopathy, and Angelman syndrome. Although alterations in the performance of MeCP2-deficient mice in specific behavioral tasks have been documented, it remains unclear whether or not MeCP2 dysfunction affects patterns of periodic behavioral and electroencephalographic (EEG) activity. The aim of the current study was therefore to determine whether a deficiency in MeCP2 is sufficient to alter the normal daily rhythmic patterns of core body temperature, gross motor activity and cortical delta power. To address this, we monitored individual wild-type and MeCP2-deficient mice in their home cage environment via telemetric recording over 24 hour cycles. Our results show that the normal daily rhythmic behavioral patterning of cortical delta wave activity, core body temperature and mobility are disrupted in one-year old female MeCP2-deficient mice. Moreover, female MeCP2-deficient mice display diminished overall motor activity, lower average core body temperature, and significantly greater body temperature fluctuation than wild-type mice in their home-cage environment. Finally, we show that the epileptiform discharge activity in female MeCP2-deficient mice is more predominant during times of behavioral activity compared to inactivity. Collectively, these results indicate that MeCP2 deficiency is sufficient to disrupt the normal patterning of daily biological rhythmic activities. PMID:22523589

Social and Environmental Factors Affecting Fecal Glucocorticoids in Wild, Female White-Faced Capuchins (Cebus capucinus)

PubMed Central

CARNEGIE, SARAH D.; FEDIGAN, LINDA M.; ZIEGLER, TONI E.

2016-01-01

Assessing glucocorticoid levels in free-ranging nonhuman primates provides a means to determine the social and environmental stress load for individuals. We investigated the effect of four proximate variables—reproductive state, season, male rank stability, and dominance rank—on the level of fecal glucocorticoids (cortisol metabolites) in eight adult female white-faced capuchin monkeys in Costa Rica. Reproductive state, season, and male rank stability significantly affected fecal glucocorticoids while female dominance rank did not. Cortisol levels were significantly higher in pregnant females as compared with lactating or other reproductive states. Cortisol levels were higher among females during the dry season compared with the wet season, suggesting a metabolic adaptation to maintain homeostasis in drier, hotter conditions. Although unfamiliar males present a greater infanticidal threat than do familiar ones, we found that females experienced higher glucocorticoid levels during male rank instability events, regardless of whether the alpha male role was taken over by a familiar or an unfamiliar male. Our findings provide important benchmark and comparative data for future studies on the variables that affect glucocorticoid levels in this species and other mammals. PMID:21506140

Social and environmental factors affecting fecal glucocorticoids in wild, female white-faced capuchins (Cebus capucinus).

PubMed

Carnegie, Sarah D; Fedigan, Linda M; Ziegler, Toni E

2011-09-01

Assessing glucocorticoid levels in free-ranging nonhuman primates provides a means to determine the social and environmental stress load for individuals. We investigated the effect of four proximate variables--reproductive state, season, male rank stability, and dominance rank--on the level of fecal glucocorticoids (cortisol metabolites) in eight adult female white-faced capuchin monkeys in Costa Rica. Reproductive state, season, and male rank stability significantly affected fecal glucocorticoids while female dominance rank did not. Cortisol levels were significantly higher in pregnant females as compared with lactating or other reproductive states. Cortisol levels were higher among females during the dry season compared with the wet season, suggesting a metabolic adaptation to maintain homeostasis in drier, hotter conditions. Although unfamiliar males present a greater infanticidal threat than do familiar ones, we found that females experienced higher glucocorticoid levels during male rank instability events, regardless of whether the alpha male role was taken over by a familiar or an unfamiliar male. Our findings provide important benchmark and comparative data for future studies on the variables that affect glucocorticoid levels in this species and other mammals. © 2011 Wiley-Liss, Inc.

Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome

PubMed Central

Plummer, J T; Evgrafov, O V; Bergman, M Y; Friez, M; Haiman, C A; Levitt, P; Aldinger, K A

2013-01-01

Single nucleotide variants (SNV) in the gene encoding the MET receptor tyrosine kinase have been associated with an increased risk for autism spectrum disorders (ASD). The MET promoter SNV rs1858830 C ‘low activity' allele is enriched in ASD, associated with reduced protein expression, and impacts functional and structural circuit connectivity in humans. To gain insight into the transcriptional regulation of MET on ASD-risk etiology, we examined an interaction between the methyl CpG-binding protein 2 (MeCP2) and the MET 5′ promoter region. Mutations in MeCP2 cause Rett syndrome (RTT), a predominantly female neurodevelopmental disorder sharing some ASD clinical symptoms. MeCP2 binds to a region of the MET promoter containing the ASD-risk SNV, and displays rs1858830 genotype-specific binding in human neural progenitor cells derived from the olfactory neuroepithelium. MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2. In the postmortem temporal cortex, a region normally enriched in MET, gene expression is reduced dramatically in females with RTT, although not due to enrichment of the rs1858830 C ‘low activity' allele. We newly identified a sex-based reduction in MET expression, with male ASD cases, but not female ASD cases compared with sex-matched controls. The experimental data reveal a prominent allele-specific regulation of MET transcription by MeCP2. The mechanisms underlying the pronounced reduction of MET in ASD and RTT temporal cortex are distinct and likely related to factors unique to each disorder, including a noted sex bias. PMID:24150225

Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome.

PubMed

Plummer, J T; Evgrafov, O V; Bergman, M Y; Friez, M; Haiman, C A; Levitt, P; Aldinger, K A

2013-10-22

Single nucleotide variants (SNV) in the gene encoding the MET receptor tyrosine kinase have been associated with an increased risk for autism spectrum disorders (ASD). The MET promoter SNV rs1858830 C 'low activity' allele is enriched in ASD, associated with reduced protein expression, and impacts functional and structural circuit connectivity in humans. To gain insight into the transcriptional regulation of MET on ASD-risk etiology, we examined an interaction between the methyl CpG-binding protein 2 (MeCP2) and the MET 5' promoter region. Mutations in MeCP2 cause Rett syndrome (RTT), a predominantly female neurodevelopmental disorder sharing some ASD clinical symptoms. MeCP2 binds to a region of the MET promoter containing the ASD-risk SNV, and displays rs1858830 genotype-specific binding in human neural progenitor cells derived from the olfactory neuroepithelium. MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2. In the postmortem temporal cortex, a region normally enriched in MET, gene expression is reduced dramatically in females with RTT, although not due to enrichment of the rs1858830 C 'low activity' allele. We newly identified a sex-based reduction in MET expression, with male ASD cases, but not female ASD cases compared with sex-matched controls. The experimental data reveal a prominent allele-specific regulation of MET transcription by MeCP2. The mechanisms underlying the pronounced reduction of MET in ASD and RTT temporal cortex are distinct and likely related to factors unique to each disorder, including a noted sex bias.

Social Brains in Context: Lesions Targeted to the Song Control System in Female Cowbirds Affect Their Social Network

PubMed Central

Maguire, Sarah E.; Schmidt, Marc F.; White, David J.

2013-01-01

Social experiences can organize physiological, neural, and reproductive function, but there are few experimental preparations that allow one to study the effect individuals have in structuring their social environment. We examined the connections between mechanisms underlying individual behavior and social dynamics in flocks of brown-headed cowbirds (Molothrus ater). We conducted targeted inactivations of the neural song control system in female subjects. Playback tests revealed that the lesions affected females' song preferences: lesioned females were no longer selective for high quality conspecific song. Instead, they reacted to all cowbird songs vigorously. When lesioned females were introduced into mixed-sex captive flocks, they were less likely to form strong pair-bonds, and they no longer showed preferences for dominant males. This in turn created a cascade of effects through the groups. Social network analyses showed that the introduction of the lesioned females created instabilities in the social structure: males in the groups changed their dominance status and their courtship patterns, and even the competitive behavior of other female group-mates was affected. These results reveal that inactivation of the song control system in female cowbirds not only affects individual behavior, but also exerts widespread effects on the stability of the entire social system. PMID:23650558

Social brains in context: lesions targeted to the song control system in female cowbirds affect their social network.

PubMed

Maguire, Sarah E; Schmidt, Marc F; White, David J

2013-01-01

Social experiences can organize physiological, neural, and reproductive function, but there are few experimental preparations that allow one to study the effect individuals have in structuring their social environment. We examined the connections between mechanisms underlying individual behavior and social dynamics in flocks of brown-headed cowbirds (Molothrus ater). We conducted targeted inactivations of the neural song control system in female subjects. Playback tests revealed that the lesions affected females' song preferences: lesioned females were no longer selective for high quality conspecific song. Instead, they reacted to all cowbird songs vigorously. When lesioned females were introduced into mixed-sex captive flocks, they were less likely to form strong pair-bonds, and they no longer showed preferences for dominant males. This in turn created a cascade of effects through the groups. Social network analyses showed that the introduction of the lesioned females created instabilities in the social structure: males in the groups changed their dominance status and their courtship patterns, and even the competitive behavior of other female group-mates was affected. These results reveal that inactivation of the song control system in female cowbirds not only affects individual behavior, but also exerts widespread effects on the stability of the entire social system.

Molecular analysis of the XLRS1 gene in 4 females affected with X-linked juvenile retinoschisis.

PubMed

Saleheen, Danish; Ali, Azam; Khanum, Shaheen; Ozair, Mohammad Z; Zaidi, Moazzam; Sethi, Muhammad J; Khan, Nadir; Frossard, Philippe

2008-10-01

X-linked juvenile retinoschisis (XLRS) is the most common cause of juvenile macular degeneration in males. Because of its X-linked mode of transmission, the disease is rare in females. In this article, we describe a mutation screen conducted on a family in which 4 female patients affected with XLRS presented with an unusually severe phenotype. DNA was extracted from peripheral blood, and the XLRS1 gene was amplified on DNA samples of all the available family members. The mutation screen was conducted by performing direct DNA sequencing using an MJ Research PTC-225 Peltier Thermal Cycler. A novel mutation, 588-593ins.C, was identified in exon 6 of the gene. The affected father was found to be heterozygous for the mutation, whereas all the female patients were homozygous for this mutation. The homozygosity of the mutation in the affected females led to severe phenotypes. The defective allele was expressed in infancy in 1 patient, whereas the disease manifested itself at variable ages in the other patients, reflecting a variation in the phenotype. This report describes a novel mutation in a family in which consanguinity has led to XLRS in 4 females. A variation in the phenotype of the disease is consistent with the published literature and suggests the involvement of genetic modifiers or environmental factors in influencing the clinical severity of the disease.

Acute exposure to ethanol on gestational day 15 affects social motivation of female offspring.

PubMed

Varlinskaya, Elena I; Mooney, Sandra M

2014-03-15

Alterations in social behavior are a hallmark of many neurodevelopmental disorders in humans. In rodents, social behavior is affected by prenatal insults. The outcomes are dependent on the timing of the insult as well as the sex and age of the animal tested. The limbic system is particularly important for social behavior, and a peak of neurogenesis within this system occurs on gestational day (G)15. Neurons appear particularly vulnerable to ethanol insult around the time they become post-mitotic. We tested the hypothesis that acute exposure to ethanol on G15 would result in significant social behavior deficits. Accordingly, Long Evans pregnant females were injected with ethanol (2.9 g/kg) or an equivalent volume of saline on G15. Offspring were assessed in a modified social interaction test on postnatal day (P) 28, P42, or P75, i.e., during early adolescence, late adolescence, or young adulthood. Prenatal ethanol exposure decreased social investigation in P28 females and transformed social preference into social avoidance in 75-day-old females. Contact behavior, play fighting, and locomotor activity differed as a function of age, but were not significantly affected by ethanol exposure. Males demonstrated significantly more contact behavior and play fighting at P42 than at P28 or P70, whereas there were no age-related changes in females. Adult females showed more locomotor activity than adult males. Overall, prenatal ethanol exposure on G15 enhanced social anxiety in females, with these effects seen in adulthood only. Copyright © 2013 Elsevier B.V. All rights reserved.

Parent-reported pain in Rett syndrome.

PubMed

Symons, Frank J; Byiers, Breanne; Tervo, Raymond C; Beisang, Arthur

2013-08-01

Clinical reports suggest that patients with Rett syndrome (RTT) live with significant chronic health issues as well as severe motor and communication impairments. Consequently, patients with RTT may be at risk for living with pain but not having it recognized. The purpose of this preliminary study was to document parent reported estimates of pain frequency, pain communication, and pain source. Caregivers of 44 patients with clinically diagnosed RTT (mean RTT age = 21.5, SD = 13.5) completed a health survey about their daughter that contained a number of items specific to pain from the Non-Communicating Children's Pain Checklist - Revised Among survey responders, 24% reported that their child had experienced pain on 8 or more days (> 1 week) in the previous 30 days. The most frequent form of pain communication was facial expression (85%) and vocalization (82%, eg, moan, cry). The most commonly reported pain source was gastro-intestinal (66%). Pain frequency was significantly (P<0.05) correlated with age (0.41), number of pain sources (0.72), and number of health problems (0.45); and the number pain sources was significantly (P<0.05) correlated with number of health problems (0.67). These preliminary results suggest that pain is a problem for a significant subgroup of patients with RTT. Almost one quarter of respondents indicated their daughters experience over a week of pain per month. The frequent health and communication issues associated with RTT suggest an increased risk that pain may be overlooked or discounted in this vulnerable population.

Personality differentially affects individual mate choice decisions in female and male Western mosquitofish (Gambusia affinis).

PubMed

Chen, Bo-Jian; Liu, Kai; Zhou, Lin-Jun; Gomes-Silva, Guilherme; Sommer-Trembo, Carolin; Plath, Martin

2018-01-01

Consistent individual differences in behavioral tendencies (animal personality) can affect individual mate choice decisions. We asked whether personality traits affect male and female mate choice decisions similarly and whether potential personality effects are consistent across different mate choice situations. Using western mosquitofish (Gambusia affinis) as our study organism, we characterized focal individuals (males and females) twice for boldness, activity, and sociability/shoaling and found high and significant behavioral repeatability. Additionally, each focal individual was tested in two different dichotomous mate choice tests in which it could choose between computer-animated stimulus fish of the opposite sex that differed in body size and activity levels, respectively. Personality had different effects on female and male mate choice: females that were larger than average showed stronger preferences for large-bodied males with increasing levels of boldness/activity (i.e., towards more proactive personality types). Males that were larger than average and had higher shoaling tendencies showed stronger preferences for actively swimming females. Size-dependent effects of personality on the strength of preferences for distinct phenotypes of potential mating partners may reflect effects of age/experience (especially in females) and social dominance (especially in males). Previous studies found evidence for assortative mate choice based on personality types or hypothesized the existence of behavioral syndromes of individuals' choosiness across mate choice criteria, possibly including other personality traits. Our present study exemplifies that far more complex patterns of personality-dependent mate choice can emerge in natural systems.

Trihexyphenidyl for acute life-threatening episodes due to a dystonic movement disorder in Rett syndrome.

PubMed

Gika, Artemis D; Hughes, Elaine; Goyal, Sushma; Sparkes, Matthew; Lin, Jean-Pierre

2010-02-15

In Rett syndrome (RS), acute life-threatening episodes (ALTEs) are usually attributed to epilepsy or autonomic dysfunction but they can represent a movement disorder (MD). We describe three girls with RS who experienced ALTEs from an early age. These were long considered epileptic until video-EEG in Patients 1 and 3 revealed their non-epileptic nature. A primary dystonic mechanism was suspected and Patients 1 and 2 were treated with Trihexyphenidyl with significantly reduced frequency of the ALTEs. Patient 3 died before Trihexyphenidyl was tried. Trihexyphenidyl in RS patients with similar presentations can modify the dystonia and prevent ALTEs. (c) 2009 Movement Disorder Society.

How visual images of chocolate affect the craving and guilt of female dieters.

PubMed

Fletcher, Ben C; Pine, Karen J; Woodbridge, Zoe; Nash, Avril

2007-03-01

This study asks whether exposure to images of chocolate induces cravings and guilty feelings in females. A further aim was to examine whether these effects are heightened in the case of dieters. The participants, 85 females, saw a series of enticing media images, either of chocolate or of non-food products. Two thirds of the sample were dieting or had dieted in the past; 15% had been on seven or more diets. After viewing the images all participants completed the Attitudes to Chocolate Questionnaire (ACQ) [Benton, Greenfield, & Morgan (1998). The development of the attitudes to chocolate questionnaire. Personality and Individual Differences, 24(4), 513-520]. The different conditions affected only those who dieted. Dieters had significantly higher ACQ scores after viewing the chocolate images than the non-dieters. It is suggested that dietary restriction increases desire for forbidden foods, in the form of craving, and may induce negative affect such as guilt, anxiety and depression.

How multiple mating by females affects sexual selection

PubMed Central

Shuster, Stephen M.; Briggs, William R.; Dennis, Patricia A.

2013-01-01

Multiple mating by females is widely thought to encourage post-mating sexual selection and enhance female fitness. We show that whether polyandrous mating has these effects depends on two conditions. Condition 1 is the pattern of sperm utilization by females; specifically, whether, among females, male mating number, m (i.e. the number of times a male mates with one or more females) covaries with male offspring number, o. Polyandrous mating enhances sexual selection only when males who are successful at multiple mating also sire most or all of each of their mates' offspring, i.e. only when Cov♂(m,o), is positive. Condition 2 is the pattern of female reproductive life-history; specifically, whether female mating number, m, covaries with female offspring number, o. Only semelparity does not erode sexual selection, whereas iteroparity (i.e. when Cov♀(m,o), is positive) always increases the variance in offspring numbers among females, which always decreases the intensity of sexual selection on males. To document the covariance between mating number and offspring number for each sex, it is necessary to assign progeny to all parents, as well as identify mating and non-mating individuals. To document significant fitness gains by females through iteroparity, it is necessary to determine the relative magnitudes of male as well as female contributions to the total variance in relative fitness. We show how such data can be collected, how often they are collected, and we explain the circumstances in which selection favouring multiple mating by females can be strong or weak. PMID:23339237

Technological aids to support choice strategies by three girls with Rett syndrome.

PubMed

Stasolla, Fabrizio; Perilli, Viviana; Di Leone, Antonia; Damiani, Rita; Albano, Vincenza; Stella, Anna; Damato, Concetta

2015-01-01

This study was aimed at extending the use of assistive technology (i.e., photocells, interface and personal computer) to support choice strategies by three girls with Rett syndrome and severe to profound developmental disabilities. A second purpose of the study was to reduce stereotypic behaviors exhibited by the participants involved (i.e., body rocking, hand washing and hand mouthing). Finally, a third goal of the study was to monitor the effects of such program on the participants' indices of happiness. The study was carried out according to a multiple probe design across responses for each participant. Results showed that the three girls increased the adaptive responses and decreased the stereotyped behaviors during intervention phases compared to baseline. Moreover, during intervention phases, the indices of happiness augmented for each girl as well. Clinical, psychological and rehabilitative implications of the findings are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Host plant affects the sexual attractiveness of the female white-spotted longicorn beetle, Anoplophora malasiaca.

PubMed

Yasui, Hiroe; Fujiwara-Tsujii, Nao

2016-07-14

Anoplophora malasiaca (Coleoptera: Cerambycidae) is a serious pest that destroys various landscape and crop trees in Japan. We evaluated the precopulatory responses of three different A. malasiaca populations collected from mandarin orange, willow and blueberry trees. Most of the males accepted mates from within the same host plant population as well as females from the willow and blueberry populations. However, significant number of males from the blueberry and willow populations rejected females from the mandarin orange population immediately after touching them with their antennae. Because all three of the female populations produced contact sex pheromones on their elytra, the females of the mandarin orange population were predicted to possess extra chemicals that repelled the males of the other two populations. β-Elemene was identified as a key component that was only found in mandarin orange-fed females and induced a rejection response in willow-fed males. Our results represent the first example of a female-acquired repellent against conspecific males of different host plant populations, indicating that the host plant greatly affects the female's sexual attractiveness.

Hormonal, biochemical, and hematological profiles in female camels (Camelus dromedarius) affected with reproductive disorders.

PubMed

Ali, A; Tharwat, M; Al-Sobayil, F A

2010-04-01

The aim of this study was to assess the blood profiles in female camels affected with common reproductive disorders. Estradiol-17beta (E(2)), progesterone (P(4)), thyroxin (T(4)), zinc (Zn), copper (Cu), calcium (Ca), phosphorus (P), magnesium (Mg), cholesterol, glucose, triglycerides, total protein, albumin, globulin, hematocrite, and total and differential white blood cell counts (WBC) were determined in blood of female camels affected with endometritis (n=15), vaginal adhesions (n=15), and ovarian cysts (n=15). Normal cyclic animals were used as controls (n=15). Diagnosis of reproductive disorders was based on transrectal palpation, ultrasonographic examination, and exploration of the vagina. Increased WBC counts (P=0.03) and a tendency for neutrophelia (P=0.05) were noted in female camels with vaginal adhesions. These animals were also characterized by having higher concentration of serum P(4) (P=0.0001), T(4) (P=0.001) and total protein (P=0.007), in comparison with female camels with endometritis, ovarian cysts, or controls. Animals having ovarian cysts with thin walls and homogenous hypoechogenic contents had greater serum E(2) (P=0.001) and P(4) (P=0.0001) than those having ovarian cysts with thick walls and non-homogenous echogenic contents. Animals with endometritis, vaginal adhesions, and ovarian cysts revealed lower serum Zn concentration than that of control group (P=0.003). Other blood parameters did not differ significantly compared to controls. In conclusion, this is the first report characterizing blood constituents in female camels with various reproductive disorders. These profiles may be valuable in clarifying the etio-pathogenesis of these disorders. Copyright 2009 Elsevier B.V. All rights reserved.

Female fecundity variation affects reproducibility of experiments on host plant preference and acceptance in a phytophagous insect

PubMed Central

Schäpers, Alexander; Petrén, Hampus; Wheat, Christopher W.; Wiklund, Christer

2017-01-01

Reproducibility is a scientific cornerstone. Many recent studies, however, describe a reproducibility crisis and call for assessments of reproducibility across scientific domains. Here, we explore the reproducibility of a classic ecological experiment—that of assessing female host plant preference and acceptance in phytophagous insects, a group in which host specialization is a key driver of diversification. We exposed multiple cohorts of Pieris napi butterflies from the same population to traditional host acceptance and preference tests on three Brassicaceae host species. Whereas the host plant rank order was highly reproducible, the propensity to oviposit on low-ranked hosts varied significantly even among cohorts exposed to similar conditions. Much variation could be attributed to among-cohort variation in female fecundity, a trait strongly correlated both to female size and to the size of the nuptial gift a female receives during mating. Small males provide small spermatophores, and in our experiment small females that mated with small males had a disproportionally low propensity to oviposit on low-ranked hosts. Hence, our results provide empirical support to the theoretical prediction that female host utilization is strongly affected by non-genetic, environmental variation, and that such variation can affect the reproducibility of ecological experiments even under seemingly identical conditions. PMID:28202813

Female brain size affects the assessment of male attractiveness during mate choice.

PubMed

Corral-López, Alberto; Bloch, Natasha I; Kotrschal, Alexander; van der Bijl, Wouter; Buechel, Severine D; Mank, Judith E; Kolm, Niclas

2017-03-01

Mate choice decisions are central in sexual selection theory aimed to understand how sexual traits evolve and their role in evolutionary diversification. We test the hypothesis that brain size and cognitive ability are important for accurate assessment of partner quality and that variation in brain size and cognitive ability underlies variation in mate choice. We compared sexual preference in guppy female lines selected for divergence in relative brain size, which we have previously shown to have substantial differences in cognitive ability. In a dichotomous choice test, large-brained and wild-type females showed strong preference for males with color traits that predict attractiveness in this species. In contrast, small-brained females showed no preference for males with these traits. In-depth analysis of optomotor response to color cues and gene expression of key opsins in the eye revealed that the observed differences were not due to differences in visual perception of color, indicating that differences in the ability to process indicators of attractiveness are responsible. We thus provide the first experimental support that individual variation in brain size affects mate choice decisions and conclude that differences in cognitive ability may be an important underlying mechanism behind variation in female mate choice.

Factors that affect self-care behaviour of female high school students with dysmenorrhoea: a cluster sampling study.

PubMed

Chang, Shu-Fang; Chuang, Mei-hua

2012-04-01

The purpose of this study was to identify factors that affect the self-care behaviour of female high school students with dysmenorrhoea. This cross-sectional study utilized a questionnaire-based survey to understand the self-care behaviour of female high school students dysmenorrhoeal, along with the factors that affect this behaviour. A cluster random sampling method was adopted and questionnaires were used for data collection. Study participants experienced a moderate level of discomfort from dysmenorrhoea, and perceived dysmenorrhoea as serious. This investigation finds that cues to action raised perceived susceptibility to dysmenorrhoea and the perceived effectiveness of self-care behaviour and, therefore, increased the adoption of self-care behaviour. Hence, school nurses should offer female high school students numerous resources to apply correct self-care behaviour. © 2012 Blackwell Publishing Asia Pty Ltd.

Defining Hand Stereotypies in Rett Syndrome: A Movement Disorders Perspective.

PubMed

Dy, Marisela E; Waugh, Jeff L; Sharma, Nutan; O'Leary, Heather; Kapur, Kush; D'Gama, Alissa M; Sahin, Mustafa; Urion, David K; Kaufmann, Walter E

2017-10-01

Hand stereotypies (HS) are a primary diagnostic criterion for Rett syndrome (RTT) but are difficult to characterize and quantify systematically. We collected video on 27 girls (2-12 years of age) with classic RTT who participated in a mecasermin trial. The present study focused exclusively on video analyses, by reviewing two five-minute windows per subject to identify the two most common HS. Three raters with expertise in movement disorders independently rated the five-minute windows using standardized terminology to determine the level of agreement. We iteratively refined the protocol in three stages to improve descriptive accuracy, categorizing HS as "central" or "peripheral," "simple" or "complex," scoring each hand separately. Inter-rater agreement was analyzed using Kappa statistics. In the initial protocol evaluating HS by video, inter-rater agreement was 20.7%. In the final protocol, inter-rater agreement for the two most frequent HS was higher than the initial protocol at 50%. Phenotypic variability makes standardized evaluation of HS in RTT a challenge; we achieved only 50% level of agreement and only for the most frequent HS. Therefore, objective measures are needed to evaluate HS. Copyright © 2017 Elsevier Inc. All rights reserved.

Disruption of DNA methylation-dependent long gene repression in Rett syndrome

PubMed Central

Gabel, Harrison W.; Kinde, Benyam Z.; Stroud, Hume; Gilbert, Caitlin S.; Harmin, David A.; Kastan, Nathaniel R.; Hemberg, Martin; Ebert, Daniel H.; Greenberg, Michael E.

2015-01-01

Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism1. MECP2 encodes a methyl-DNA-binding protein2 that has been proposed to function as a transcriptional repressor, but despite numerous studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 regulates transcription3–9. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain. PMID:25762136

Alterations in the cholinergic system of brain stem neurons in a mouse model of Rett syndrome.

PubMed

Oginsky, Max F; Cui, Ningren; Zhong, Weiwei; Johnson, Christopher M; Jiang, Chun

2014-09-15

Rett syndrome is an autism-spectrum disorder resulting from mutations to the X-linked gene, methyl-CpG binding protein 2 (MeCP2), which causes abnormalities in many systems. It is possible that the body may develop certain compensatory mechanisms to alleviate the abnormalities. The norepinephrine system originating mainly in the locus coeruleus (LC) is defective in Rett syndrome and Mecp2-null mice. LC neurons are subject to modulation by GABA, glutamate, and acetylcholine (ACh), providing an ideal system to test the compensatory hypothesis. Here we show evidence for potential compensatory modulation of LC neurons by post- and presynaptic ACh inputs. We found that the postsynaptic currents of nicotinic ACh receptors (nAChR) were smaller in amplitude and longer in decay time in the Mecp2-null mice than in the wild type. Single-cell PCR analysis showed a decrease in the expression of α3-, α4-, α7-, and β3-subunits and an increase in the α5- and α6-subunits in the mutant mice. The α5-subunit was present in many of the LC neurons with slow-decay nAChR currents. The nicotinic modulation of spontaneous GABAA-ergic inhibitory postsynaptic currents in LC neurons was enhanced in Mecp2-null mice. In contrast, the nAChR manipulation of glutamatergic input to LC neurons was unaffected in both groups of mice. Our current-clamp studies showed that the modulation of LC neurons by ACh input was reduced moderately in Mecp2-null mice, despite the major decrease in nAChR currents, suggesting possible compensatory processes may take place, thus reducing the defects to a lesser extent in LC neurons. Copyright © 2014 the American Physiological Society.

Mitochondrial dysfunction as a central actor in intellectual disability-related diseases: an overview of Down syndrome, autism, Fragile X and Rett syndrome.

PubMed

Valenti, Daniela; de Bari, Lidia; De Filippis, Bianca; Henrion-Caude, Alexandra; Vacca, Rosa Anna

2014-10-01

Clinical manifestations typical of mitochondrial diseases are often present in various genetic syndromes associated with intellectual disability, a condition leading to deficit in cognitive functions and adaptive behaviors. Until now, the causative mechanism leading to intellectual disability is unknown and the progression of the condition is poorly understood. We first report latest advances on genetic and environmental regulation of mitochondrial function and its role in brain development. Starting from the structure, function and regulation of the oxidative phosphorylation apparatus, we review how mitochondrial biogenesis and dynamics play a central role in neurogenesis and neuroplasticity. We then discuss how dysfunctional mitochondria and alterations in reactive oxygen species homeostasis are potentially involved in the pathogenesis of various neurodevelopmental syndromes with a special focus on Down, Rett, Fragile X syndromes and autism spectrum disorders. Finally, we review and suggest novel therapeutic approaches aimed at improving intellectual disability by activating mitochondrial function and reducing oxidative stress to amiliorate the quality of life in the subjects affected. Copyright © 2014 Elsevier Ltd. All rights reserved.

MeCP2 deficiency in Rett syndrome causes epigenetic aberrations at the PWS/AS imprinting center that affects UBE3A expression.

PubMed

Makedonski, Kirill; Abuhatzira, Liron; Kaufman, Yotam; Razin, Aharon; Shemer, Ruth

2005-04-15

Rett syndrome (RS) is a severe and progressive neurodevelopmental disorder caused by heterozygous mutations in the X-linked methyl CpG binding protein 2 (MeCP2) gene. MeCP2 is a nuclear protein that binds specifically to methylated DNA and functions as a general transcription repressor in the context of chromatin remodeling complexes. RS shares clinical features with those of Angelman syndrome (AS), an imprinting neurodevelopmental disorder. In AS patients, the maternally expressed copy of UBE3A that codes for the ubiquitin protein ligase 3A (E6-AP) is repressed. The similar phenotype of these two syndromes led us to hypothesize that part of the RS phenotype is due to MeCP2-associated silencing of UBE3A. Indeed, UBE3A mRNA and protein are shown here to be significantly reduced in human and mouse MECP2 deficient brains. This reduced UBE3A level was associated with biallelic production of the UBE3A antisense RNA. In addition, MeCP2 deficiency resulted in elevated histone H3 acetylation and H3(K4) methylation and reduced H3(K9) methylation at the PWS/AS imprinting center, with no effect on DNA methylation or SNRPN expression. We conclude, therefore, that MeCP2 deficiency causes epigenetic aberrations at the PWS imprinting center. These changes in histone modifications result in loss of imprinting of the UBE3A antisense gene in the brain, increase in UBE3A antisense RNA level and, consequently reduction in UBE3A production.

Cytokines profile and peripheral blood mononuclear cells morphology in Rett and autistic patients.

PubMed

Pecorelli, Alessandra; Cervellati, Franco; Belmonte, Giuseppe; Montagner, Giulia; Waldon, PhiAnh; Hayek, Joussef; Gambari, Roberto; Valacchi, Giuseppe

2016-01-01

A potential role for immune dysfunction in autism spectrum disorders (ASD) has been well established. However, immunological features of Rett syndrome (RTT), a genetic neurodevelopmental disorder closely related to autism, have not been well addressed yet. By using multiplex Luminex technology, a panel of 27 cytokines and chemokines was evaluated in serum from 10 RTT patients with confirmed diagnosis of MECP2 mutation (typical RTT), 12 children affected by classic autistic disorder and 8 control subjects. The cytokine/chemokine gene expression was assessed by real time PCR on mRNA of isolated peripheral blood mononuclear cells (PBMCs). Moreover, ultrastructural analysis of PBMCs was performed using transmission electron microscopy (TEM). Significantly higher serum levels of interleukin-8 (IL-8), IL-9, IL-13 were detected in RTT compared to control subjects, and IL-15 shows a trend toward the upregulation in RTT. In addition, IL-1β and VEGF were the only down-regulated cytokines in autistic patients with respect to RTT. No difference in cytokine/chemokine profile between autistic and control groups was detected. These data were also confirmed by ELISA real time PCR. At the ultrastructural level, the most severe morphological abnormalities were observed in mitochondria of both RTT and autistic PBMCs. In conclusion, our study shows a deregulated cytokine/chemokine profile together with morphologically altered immune cells in RTT. Such abnormalities were not quite as evident in autistic subjects. These findings indicate a possible role of immune dysfunction in RTT making the clinical features of this pathology related also to the immunology aspects, suggesting, therefore, novel possible therapeutic interventions for this disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dominance rank causally affects personality and glucocorticoid regulation in female rhesus macaques

PubMed Central

Kohn, Jordan N.; Snyder-Mackler, Noah; Barreiro, Luis B.; Johnson, Zachary P.; Tung, Jenny; Wilson, Mark E.

2017-01-01

Low social status is frequently associated with heightened exposure to social stressors and altered glucocorticoid regulation by the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, personality differences can affect how individuals behave in response to social conditions, and thus may aggravate or protect against the effects of low status on HPA function. Disentangling the relative importance of personality from the effects of the social environment on the HPA axis has been challenging, since social status can predict aspects of behavior, and both can remain stable across the lifespan. To do so here, we studied an animal model of social status and social behavior, the rhesus macaque (Macaca mulatta). We performed two sequential experimental manipulations of dominance rank (i.e., social status) in 45 adult females, allowing us to characterize personality and glucocorticoid regulation (based on sensitivity to the exogenous glucocorticoid dexamethasone) in each individual while she occupied two different dominance ranks. We identified two behavioral characteristics, termed ‘social approachability’ and ‘boldness,’ which were highly social status-dependent. Social approachability and a third dimension, anxiousness, were also associated with cortisol dynamics in low status females, suggesting that behavioral tendencies may sensitize individuals to the effects of low status on HPA axis function. Finally, we found that improvements in dominance rank increased dexamethasone-induced acute cortisol suppression and glucocorticoid negative feedback. Our findings indicate that social status causally affects both behavioral tendencies and glucocorticoid regulation, and that some behavioral tendencies also independently affect cortisol levels, beyond the effects of rank. Together, they highlight the importance of considering personality and social status together when investigating their effects on HPA axis function. PMID:27639059

Dominance rank causally affects personality and glucocorticoid regulation in female rhesus macaques.

PubMed

Kohn, Jordan N; Snyder-Mackler, Noah; Barreiro, Luis B; Johnson, Zachary P; Tung, Jenny; Wilson, Mark E

2016-12-01

Low social status is frequently associated with heightened exposure to social stressors and altered glucocorticoid regulation by the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, personality differences can affect how individuals behave in response to social conditions, and thus may aggravate or protect against the effects of low status on HPA function. Disentangling the relative importance of personality from the effects of the social environment on the HPA axis has been challenging, since social status can predict aspects of behavior, and both can remain stable across the lifespan. To do so here, we studied an animal model of social status and social behavior, the rhesus macaque (Macaca mulatta). We performed two sequential experimental manipulations of dominance rank (i.e., social status) in 45 adult females, allowing us to characterize personality and glucocorticoid regulation (based on sensitivity to the exogenous glucocorticoid dexamethasone) in each individual while she occupied two different dominance ranks. We identified two behavioral characteristics, termed 'social approachability' and 'boldness,' which were highly social status-dependent. Social approachability and a third dimension, anxiousness, were also associated with cortisol dynamics in low status females, suggesting that behavioral tendencies may sensitize individuals to the effects of low status on HPA axis function. Finally, we found that improvements in dominance rank increased dexamethasone-induced acute cortisol suppression and glucocorticoid negative feedback. Our findings indicate that social status causally affects both behavioral tendencies and glucocorticoid regulation, and that some behavioral tendencies also independently affect cortisol levels, beyond the effects of rank. Together, they highlight the importance of considering personality and social status together when investigating their effects on HPA axis function. Copyright © 2016 Elsevier Ltd. All rights reserved.

Factors Affecting Female Participation in Education in Seven Developing Countries. Second Edition. Education Research Paper.

ERIC Educational Resources Information Center

Brock, Colin; Cammish, Nadine

Factors affecting female participation in education in seven developing countries were examined through field visits to the following countries: Bangladesh, Cameroon, India, Jamaica, Seychelles, Sierra Leone, and Vanuatu. In each country, researchers interviewed key personnel, consulted local documentation, and conducted two empirical surveys…

Rapid genotyping of common MeCP2 mutations with an electronic DNA microchip using serial differential hybridization.

PubMed

Thistlethwaite, William A; Moses, Linda M; Hoffbuhr, Kristen C; Devaney, Joseph M; Hoffman, Eric P

2003-05-01

Rett syndrome is a neurodevelopmental disorder that affects females almost exclusively, and in which eight common point mutations on the X-linked MeCP2 gene are knows to cause over 70% of mutation-positive cases. We explored the use of a novel platform to detect the eight common mutations in Rett syndrome patients to expedite and simplify the process of identification of known genotypes. The Nanogen workstation consists of a two-color assay based on electric hybridization and thermal discrimination, all performed on an electronically active NanoChip. This genotyping platform was tested on 362 samples of a pre-determined genotype, which had been previously identified by a combination of DHPLC (denaturing high performance liquid chromatography) and direct sequencing. This genotyping technique proved to be rapid, facile, and displayed a specificity of 100% with 3% ambiguity. In addition, we present consecutive testing of seven mutations on a single pad of the NanoChip. This was accomplished by tagging down two amplimers together and serially hybridizing for seven different loci, allowing us to genotype samples for seven of the eight common Rett mutations on a single pad. This novel method displayed the same level of specificity and accuracy as the single amplimer reactions, and proved to be faster and more economical.

Early progressive encephalopathy in boys and MECP2 mutations.

PubMed

Kankirawatana, P; Leonard, H; Ellaway, C; Scurlock, J; Mansour, A; Makris, C M; Dure, L S; Friez, M; Lane, J; Kiraly-Borri, C; Fabian, V; Davis, M; Jackson, J; Christodoulou, J; Kaufmann, W E; Ravine, D; Percy, A K

2006-07-11

MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

A novel STXBP1 mutation causes typical Rett syndrome in a Japanese girl.

PubMed

Yuge, Kotaro; Iwama, Kazuhiro; Yonee, Chihiro; Matsufuji, Mayumi; Sano, Nozomi; Saikusa, Tomoko; Yae, Yukako; Yamashita, Yushiro; Mizuguchi, Takeshi; Matsumoto, Naomichi; Matsuishi, Toyojiro

2018-06-01

Rett syndrome (RTT) is a neurodevelopmental disorder mostly caused by mutations in Methyl-CpG-binding protein 2 (MECP2); however, mutations in various other genes may lead to RTT-like phenotypes. Here, we report the first case of a Japanese girl with RTT caused by a novel syntaxin-binding protein 1 (STXBP1) frameshift mutation (c.60delG, p.Lys21Argfs*16). She showed epilepsy at one year of age, regression of acquired psychomotor abilities thereafter, and exhibited stereotypic hand and limb movements at 3 years of age. Her epilepsy onset was earlier than is typical for RTT patients. However, she fully met the 2010 diagnostic criteria of typical RTT. STXBP1 mutations cause early infantile epileptic encephalopathy (EIEE), various intractable epilepsies, and neurodevelopmental disorders. However, the case described here presented a unique clinical presentation of typical RTT without EIEE and a novel STXBP1 mutation. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Publicizing female athletes' weights: implications for female psychology undergraduates acting as spectators.

PubMed

Holm-Denoma, Jill; Smith, April; Waesche, Matthew

2014-09-01

The purpose of this study was to examine the effects of including female athletes' weights in athletic event programs on female spectators' body image, eating disorder symptoms, self-esteem, and affective state and to investigate whether the magnitude of the athletes' reported weights had differential effects on female spectators (i.e., do female spectators who view heavier athletes respond differently than those who view less heavy athletes?). We used an experimental design to examine hypotheses derived from competing theories to determine whether exposure to female athletes of varying weight would adversely or beneficially impact female undergraduates (N = 152) who served as athletic event spectators. Analyses indicated that in this simulated study, female spectators' body image, eating disorder symptoms, self-esteem, and affective states were not impacted by the presence or by the magnitude of female athletes' weights in athletic event programs. The results imply that including athletes' weights in game-day programs at women's athletic events does not affect female spectators on an individual level.

Female Mecp2+/− mice display robust behavioral deficits on two different genetic backgrounds providing a framework for pre-clinical studies

PubMed Central

Samaco, Rodney C.; McGraw, Christopher M.; Ward, Christopher S.; Sun, Yaling; Neul, Jeffrey L.; Zoghbi, Huda Y.

2013-01-01

Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the gene encoding the transcriptional modulator methyl-CpG-binding protein 2 (MeCP2). Typical RTT primarily affects girls and is characterized by a brief period of apparently normal development followed by the loss of purposeful hand skills and language, the onset of anxiety, hand stereotypies, autistic features, seizures and autonomic dysfunction. Mecp2 mouse models have extensively been studied to demonstrate the functional link between MeCP2 dysfunction and RTT pathogenesis. However, the majority of studies have focused primarily on the molecular and behavioral consequences of the complete absence of MeCP2 in male mice. Studies of female Mecp2+/− mice have been limited because of potential phenotypic variability due to X chromosome inactivation effects. To determine whether reproducible and reliable phenotypes can be detected Mecp2+/− mice, we analyzed Mecp2+/− mice of two different F1 hybrid isogenic backgrounds and at young and old ages using several neurobehavioral and physiological assays. Here, we report a multitude of phenotypes in female Mecp2+/− mice, some presenting as early as 5 weeks of life. We demonstrate that Mecp2+/− mice recapitulate several aspects of typical RTT and show that mosaic expression of MeCP2 does not preclude the use of female mice in behavioral and molecular studies. Importantly, we uncover several behavioral abnormalities that are present in two genetic backgrounds and report on phenotypes that are unique to one background. These findings provide a framework for pre-clinical studies aimed at improving the constellation of phenotypes in a mouse model of RTT. PMID:23026749

Effect of Sarizotan, a 5-HT1a and D2-like receptor agonist, on respiration in three mouse models of Rett syndrome.

PubMed

Abdala, Ana P; Lioy, Daniel T; Garg, Saurabh K; Knopp, Sharon J; Paton, Julian F R; Bissonnette, John M

2014-06-01

Disturbances in respiration are common and debilitating features of Rett syndrome (RTT). A previous study showed that the 5-HT1a receptor agonist (R)-(+)-8-hydroxy-dipropyl-2-aminotetralin hydrobromide (8-OH-DPAT) significantly reduced the incidence of apnea and the irregular breathing pattern in a mouse model of the disorder. 8-OH-DPAT, however, is not available for clinical practice. Sarizotan, a full 5-HT1a agonist and a dopamine D2-like agonist/partial agonist, has been used in clinical trials for the treatment of l-dopa-induced dyskinesia. The purpose of this study was to evaluate the effects of sarizotan on respiration and locomotion in mouse models of RTT. Studies were performed in Bird and Jaenisch strains of methyl-CpG-binding protein 2--deficient heterozygous female and Jaenisch strain Mecp2 null male mice and in knock-in heterozygous female mice of a common nonsense mutation (R168X). Respiratory pattern was determined with body plethysmography, and locomotion was determined with open-field recording. Sarizotan or vehicle was administered 20 minutes before a 30-minute recording of respiratory pattern or motor behavior. In separate studies, a crossover design was used to administer the drug for 7 and for 14 days. Sarizotan reduced the incidence of apnea in all three RTT mouse models to approximately 15% of their pretreatment levels. The irregular breathing pattern was corrected to that of wild-type littermates. When administered for 7 or 14 days, apnea decreased to 25 to 33% of the incidence seen with vehicle. This study indicates that the clinically approved drug sarizotan is an effective treatment for respiratory disorders in mouse models of RTT.

Factors affecting interest in orthopedics among female medical students: a prospective analysis.

PubMed

Baldwin, Keith; Namdari, Surena; Bowers, Andrea; Keenan, Mary Ann; Levin, L Scott; Ahn, Jaimo

2011-12-06

The field of orthopedics has a limited ability to recruit high-quality female applicants. The purpose of this study was to determine whether early exposure to the field affects a woman's decision to pursue orthopedics. We performed a prospective, nonrandomized cohort study between academic years 2005 and 2009 and compared interest in orthopedic surgery among female (n=271) and male (n=71) medical students at 2 urban teaching institutions. Elective lectures and orthopedic literature were distributed via e-mail to the study participants. These materials included articles published in the medical literature, materials produced and distributed by the American Academy of Orthopaedic Surgeons, and Web sites providing educational materials. The primary outcome was the likelihood of application for orthopedic residency. We studied the influence of demographics, exposure, and attitudes on interest in pursuing an orthopedic career. Men had a significantly higher baseline level of interest in orthopedic surgery than women (P=.005). Younger age (P<.001) and personal (P<.001), independent (P<.001), and school (P=.023) exposures to orthopedics were significantly related to interest among women. At final follow-up, total personal exposures (P=.003) and total independent exposures (P<.001) in the form of our literature and lectures were correlated with final interest in women. Female interest was decreased by the long hours, physical demands, and predominantly male nature of the field. Early exposure to orthopedic educational resources may be useful in generating female interest. Perceptions and attitudes regarding orthopedic surgery must to be changed to attract the best and brightest minds, regardless of sex. Copyright © 2011, SLACK Incorporated.

Female teachers' math anxiety affects girls' math achievement.

PubMed

Beilock, Sian L; Gunderson, Elizabeth A; Ramirez, Gerardo; Levine, Susan C

2010-02-02

People's fear and anxiety about doing math--over and above actual math ability--can be an impediment to their math achievement. We show that when the math-anxious individuals are female elementary school teachers, their math anxiety carries negative consequences for the math achievement of their female students. Early elementary school teachers in the United States are almost exclusively female (>90%), and we provide evidence that these female teachers' anxieties relate to girls' math achievement via girls' beliefs about who is good at math. First- and second-grade female teachers completed measures of math anxiety. The math achievement of the students in these teachers' classrooms was also assessed. There was no relation between a teacher's math anxiety and her students' math achievement at the beginning of the school year. By the school year's end, however, the more anxious teachers were about math, the more likely girls (but not boys) were to endorse the commonly held stereotype that "boys are good at math, and girls are good at reading" and the lower these girls' math achievement. Indeed, by the end of the school year, girls who endorsed this stereotype had significantly worse math achievement than girls who did not and than boys overall. In early elementary school, where the teachers are almost all female, teachers' math anxiety carries consequences for girls' math achievement by influencing girls' beliefs about who is good at math.

Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs

PubMed Central

Galano, Jean-Marie; Guerranti, Roberto; Rossi, Marcello; Ciccoli, Lucia; Hayek, Joussef

2015-01-01

An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2) or, more rarely, cyclin-dependent kinase-like 5 (CDKL5). To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg) response, as well as chemokines, were investigated in MECP2- (MECP2-RTT) (n = 16) and CDKL5-Rett syndrome (CDKL5-RTT) (n = 8), before and after ω-3 polyunsaturated fatty acids (PUFAs) supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1- and Th2-related cytokines (except for IL-4) were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system. PMID:26236424

Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs.

PubMed

Leoncini, Silvia; De Felice, Claudio; Signorini, Cinzia; Zollo, Gloria; Cortelazzo, Alessio; Durand, Thierry; Galano, Jean-Marie; Guerranti, Roberto; Rossi, Marcello; Ciccoli, Lucia; Hayek, Joussef

2015-01-01

An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2) or, more rarely, cyclin-dependent kinase-like 5 (CDKL5). To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg) response, as well as chemokines, were investigated in MECP2- (MECP2-RTT) (n = 16) and CDKL5-Rett syndrome (CDKL5-RTT) (n = 8), before and after ω-3 polyunsaturated fatty acids (PUFAs) supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1- and Th2-related cytokines (except for IL-4) were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system.

Sociocultural and Motivational Factors Affecting Asian American Females Studying Physics and Engineering in High School

ERIC Educational Resources Information Center

Sha, Saliha L.

2012-01-01

This quantitative study investigated whether and to what extent the motivational and sociocultural factors affect female Asian American high school physics students' achievement, their intended major in college, and their planned career goals at work fields. A survey of 62 questions, extracted from subscales of AAMAS,STPQ and PSE, were…

Undergraduate African American females in the sciences: A qualitative study of student experiences affecting academic success and persistence

NASA Astrophysics Data System (ADS)

Essien-Wood, Idara R.

Given the lack of literature on Undergraduate African American females in the sciences (UAAFS), this study sought to explicate their experiences at one large, predominantly White, Research I institution in the southwestern United States. In particular, the purpose of this study was to identify factors that affect the academic success and persistence of Black females in the natural and physical sciences. Data was collected via in-depth, semi-structured interviews with 15 Black female science majors. Findings from this study identified several supportive mechanisms for academic success: family, religion, teaching assistants and friends. Also identified were seven barriers to academic success: employment, lack of diversity, cultural dissonance, unwelcoming Research I environment, faculty, advisors, classmates, and lab groups. Further, an analysis of students' responses revealed numerous instances of racial and gender micro-aggressions. Recommendations are provided to address factors identified as affecting student academic success and persistence as well as a culture of micro-aggressive behavior.

Leber's Hereditary Optic Neuropathy Affects Only Female Matrilineal Relatives in Two Chinese Families

PubMed Central

Qu, Jia; Wang, Ying; Tong, Yi; Zhou, Xiangtian; Zhao, Fuxin; Yang, Li; Zhang, Shoukang; Zhang, Juanjuan; West, Constance E.; Guan, Min-Xin

2010-01-01

Purpose. The purpose of this study was to investigate the role of modifier factors in the expression of Leber's hereditary optic neuropathy (LHON). Methods. Thirty-five subjects from two Han Chinese families with maternally transmitted LHON underwent a clinical and genetic evaluation and molecular analysis of mitochondrial (mt)DNA. Results. Matrilineal relatives in the two Chinese families exhibited a wide range of severity in visual impairment, from blindness to nearly normal vision. Very strikingly, all nine affected individuals of 21 matrilineal relatives (13 females/8 males) were female, which translates to 33% and 57% of penetrance for optic neuropathy in the two families. The average age at onset was 22 and 25 years. These observations were in contrast with typical features in many LHON pedigrees that have a predominance of affected males. Molecular analysis of their mtDNAs identified the homoplasmic ND4 G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M1 and M10a. Of other variants, the L175F variant in CO3; the I58V variant in ND6; and the I189V, L292R, and S297A variants in CYTB were located at highly conserved residues of polypeptides. Conclusions. Only female matrilineal relatives with a wide range of penetrance, severity, and age at onset of optic neuropathy in these two Chinese pedigrees showed the involvement of X-linked or autosomal recessive modifier genes in the phenotypic manifestation of the G11778A mutation. Furthermore, mitochondrial haplogroup-specific variants, together with epigenetic and environmental factors, may contribute to the phenotypic manifestation of the primary LHON-associated G11778A mutation in these pedigrees. PMID:20435583

Reduced striatal activation in females with major depression during the processing of affective stimuli.

PubMed

Connolly, Megan E; Gollan, Jackie K; Cobia, Derin; Wang, Xue

2015-09-01

The extent to which affective reactivity and associated neural underpinnings are altered by depression remains equivocal. This study assessed striatal activation in fifty-one unmedicated female participants meeting DSM-IV criteria for Major Depressive Disorder (MDD) and 61 age-matched healthy females (HC) aged 17-63 years. Participants completed an affective reactivity functional magnetic resonance imaging task. Data were preprocessed using SPM8, and region-of-interest analyses were completed using MarsBaR to extract caudate, putamen, and nucleus accumbens (NAcc) activation. General linear repeated measure ANOVAs were used to assess group differences and correlational analyses were used to measure the association between activation, depression severity, and anhedonia. Main effects of hemisphere, valence, and group status were observed, with MDD participants demonstrating decreased striatal activation compared with HC. Across groups and valence types, the left hemisphere demonstrated greater activation than the right hemisphere in the putamen and nucleus accumbens, whereas the right hemisphere demonstrated greater activation than the left in the caudate. Additionally, unpleasant stimuli elicited greater activation than pleasant and neutral stimuli in the caudate and putamen, and unpleasant stimuli elicited greater activation than neutral stimuli in the NAcc. There were no significant associations between activation, depression severity, and anhedonia. Overall, depression was characterized by reduced affective reactivity in the striatum, regardless of stimuli valence, supporting the emotion context insensitivity model of depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Sarizotan, a 5-HT1a and D2-Like Receptor Agonist, on Respiration in Three Mouse Models of Rett Syndrome

PubMed Central

Abdala, Ana P.; Lioy, Daniel T.; Garg, Saurabh K.; Knopp, Sharon J.; Paton, Julian F. R.

2014-01-01

Disturbances in respiration are common and debilitating features of Rett syndrome (RTT). A previous study showed that the 5-HT1a receptor agonist (R)-(+)-8-hydroxy-dipropyl-2-aminotetralin hydrobromide (8-OH-DPAT) significantly reduced the incidence of apnea and the irregular breathing pattern in a mouse model of the disorder. 8-OH-DPAT, however, is not available for clinical practice. Sarizotan, a full 5-HT1a agonist and a dopamine D2–like agonist/partial agonist, has been used in clinical trials for the treatment of l-dopa–induced dyskinesia. The purpose of this study was to evaluate the effects of sarizotan on respiration and locomotion in mouse models of RTT. Studies were performed in Bird and Jaenisch strains of methyl-CpG–binding protein 2-–deficient heterozygous female and Jaenisch strain Mecp2 null male mice and in knock-in heterozygous female mice of a common nonsense mutation (R168X). Respiratory pattern was determined with body plethysmography, and locomotion was determined with open-field recording. Sarizotan or vehicle was administered 20 minutes before a 30-minute recording of respiratory pattern or motor behavior. In separate studies, a crossover design was used to administer the drug for 7 and for 14 days. Sarizotan reduced the incidence of apnea in all three RTT mouse models to approximately 15% of their pretreatment levels. The irregular breathing pattern was corrected to that of wild-type littermates. When administered for 7 or 14 days, apnea decreased to 25 to 33% of the incidence seen with vehicle. This study indicates that the clinically approved drug sarizotan is an effective treatment for respiratory disorders in mouse models of RTT. PMID:24351104

Vitellogenin knockdown strongly affects cotton boll weevil egg viability but not the number of eggs laid by females.

PubMed

Coelho, Roberta R; de Souza Júnior, José Dijair Antonino; Firmino, Alexandre A P; de Macedo, Leonardo L P; Fonseca, Fernando C A; Terra, Walter R; Engler, Gilbert; de Almeida Engler, Janice; da Silva, Maria Cristina M; Grossi-de-Sa, Maria Fatima

2016-09-01

Vitellogenin (Vg), a yolk protein precursor, is the primary egg nutrient source involved in insect reproduction and embryo development. The Cotton Boll weevil (CBW) Anthonomus grandis Boheman, the most important cotton pest in Americas, accumulates large amounts of Vg during reproduction. However, the precise role of this protein during embryo development in this insect remains unknown. Herein, we investigated the effects of vitellogenin (AgraVg) knockdown on the egg-laying and egg viability in A. grandis females, and also characterized morphologically the unviable eggs. AgraVg transcripts were found during all developmental stages of A. grandis, with highest abundance in females. Silencing of AgraVg culminated in a significant reduction in transcript amount, around 90%. Despite this transcriptional reduction, egg-laying was not affected in dsRNA-treated females but almost 100% of the eggs lost their viability. Eggs from dsRNA-treated females showed aberrant embryos phenotype suggesting interference at different stages of embryonic development. Unlike for other insects, the AgraVg knockdown did not affect the egg-laying ability of A. grandis, but hampered A. grandis reproduction by perturbing embryo development. We concluded that the Vg protein is essential for A. grandis reproduction and a good candidate to bio-engineer the resistance against this devastating cotton pest.

Loss of MeCP2 in the rat models regression, impaired sociability and transcriptional deficits of Rett syndrome

PubMed Central

Veeraragavan, Surabi; Wan, Ying-Wooi; Connolly, Daniel R.; Hamilton, Shannon M.; Ward, Christopher S.; Soriano, Sirena; Pitcher, Meagan R.; McGraw, Christopher M.; Huang, Sharon G.; Green, Jennie R.; Yuva, Lisa A.; Liang, Agnes J.; Neul, Jeffrey L.; Yasui, Dag H.; LaSalle, Janine M.; Liu, Zhandong; Paylor, Richard; Samaco, Rodney C.

2016-01-01

Mouse models of the transcriptional modulator Methyl-CpG-Binding Protein 2 (MeCP2) have advanced our understanding of Rett syndrome (RTT). RTT is a ‘prototypical’ neurodevelopmental disorder with many clinical features overlapping with other intellectual and developmental disabilities (IDD). Therapeutic interventions for RTT may therefore have broader applications. However, the reliance on the laboratory mouse to identify viable therapies for the human condition may present challenges in translating findings from the bench to the clinic. In addition, the need to identify outcome measures in well-chosen animal models is critical for preclinical trials. Here, we report that a novel Mecp2 rat model displays high face validity for modelling psychomotor regression of a learned skill, a deficit that has not been shown in Mecp2 mice. Juvenile play, a behavioural feature that is uniquely present in rats and not mice, is also impaired in female Mecp2 rats. Finally, we demonstrate that evaluating the molecular consequences of the loss of MeCP2 in both mouse and rat may result in higher predictive validity with respect to transcriptional changes in the human RTT brain. These data underscore the similarities and differences caused by the loss of MeCP2 among divergent rodent species which may have important implications for the treatment of individuals with disease-causing MECP2 mutations. Taken together, these findings demonstrate that the Mecp2 rat model is a complementary tool with unique features for the study of RTT and highlight the potential benefit of cross-species analyses in identifying potential disease-relevant preclinical outcome measures. PMID:27365498

A cognitive-perceptual model of symptom perception in males and females: the roles of negative affect, selective attention, health anxiety and psychological job demands.

PubMed

Goodwin, Laura; Fairclough, Stephen H; Poole, Helen M

2013-06-01

Kolk et al.'s model of symptom perception underlines the effects of trait negative affect, selective attention and external stressors. The current study tested this model in 263 males and 498 females from an occupational sample. Trait negative affect was associated with symptom reporting in females only, and selective attention and psychological job demands were associated with symptom reporting in both genders. Health anxiety was associated with symptom reporting in males only. Future studies might consider the inclusion of selective attention, which was more strongly associated with symptom reporting than negative affect. Psychological job demands appear to influence symptom reporting in both males and females.

Family functioning mediates adaptation in caregivers of individuals with Rett syndrome.

PubMed

Lamb, Amanda E; Biesecker, Barbara B; Umstead, Kendall L; Muratori, Michelle; Biesecker, Leslie G; Erby, Lori H

2016-11-01

The objective of this study was to investigate factors related to family functioning and adaptation in caregivers of individuals with Rett syndrome (RS). A cross-sectional quantitative survey explored the relationships between demographics, parental self-efficacy, coping methods, family functioning and adaptation. A forward-backward, step-wise model selection procedure was used to evaluate variables associated with both family functioning and adaptation. Analyses also explored family functioning as a mediator of the relationship between other variables and adaptation. Bivariate analyses (N=400) revealed that greater parental self-efficacy, a greater proportion of problem-focused coping, and a lesser proportion of emotion-focused coping were associated with more effective family functioning. In addition, these key variables were significantly associated with greater adaptation, as was family functioning, while controlling for confounders. Finally, regression analyses suggest family functioning as a mediator of the relationships between three variables (parental self-efficacy, problem-focused coping, and emotion-focused coping) with adaptation. This study demonstrates the potentially predictive roles of expectations and coping methods and the mediator role of family functioning in adaptation among caregivers of individuals with RS, a chronic developmental disorder. A potential target for intervention is strengthening of caregiver competence in the parenting role to enhance caregiver adaptation. Published by Elsevier Ireland Ltd.

Predictors affecting breast self-examination practice among undergraduate female students in Klang Valley, Malaysia.

PubMed

Akhtari-Zavare, Mehrnoosh; Lattif, Latiffah A; Juni, Muhamad Hanafiah; Md Said, Salmiah; Ismail, Irmi Zarina

2015-12-01

Breast cancer is the most common cancer among women worldwide, including Malaysia. In developing countries, predictors affecting breast self-examination (BSE) practice are different. This cross-sectional study was conducted to determine the prevalence of BSE practice and the predictors affecting BSE practice among undergraduate female students in Klang Valley, Malaysia. A cross-sectional study was conducted among 820 female undergraduate students to assess the BSE performance and related determinants of BSE practice in Klang Valley, Malaysia. Data were collected via a self-administered structured questionnaire that was developed for this study. The mean age of the respondents was 21.7 ± 1.2 years old. Most of them were single (96.8%), Malay (91.9%) and 19.6% of the participants performed BSE regularly. Multivariate logistic regression modeling revealed that BSE performance was more likely among women who have checked their breast with a doctor (odds ratio = 2.04, P = 0.00), and women who have personal history of breast disease (odds ratio = 4.43, P = 0.03). The findings showed a low BSE practice rate among young Malaysian women. Hence, the community's breast health awareness is needed to improve breast cancer prevention among young Malaysian women. © 2015 Japan Society of Obstetrics and Gynecology.

Cross-Fostering of Male Mice Subtly Affects Female Olfactory Preferences

PubMed Central

Liu, Ying-Juan; Zhang, Yao-Hua; Li, Lai-Fu; Du, Rui-Qing; Zhang, Jin-Hua; Zhang, Jian-Xu

2016-01-01

The maternal environment has been shown to influence female olfactory preferences through early chemosensory experience. However, little is known about the influence of the maternal environment on chemosignals. In this study, we used two inbred mouse strains, C57BL/6 (C57) and BALB/c (BALB), and explored whether adoption could alter male chemosignals and thus influence female olfactory preferences. In Experiment 1, C57 pups were placed with BALB dams. Adult BALB females then served as the subjects in binary choice tests between paired male urine odours (BALB vs. C57, BALB vs. adopted C57 and C57 vs. adopted C57). In Experiment 2, BALB pups were placed with C57 dams, and C57 females served as the subjects in binary choice tests between paired male urine odours (C57 vs. BALB, C57 vs. adopted BALB, and BALB vs. adopted BALB). In both experiments, we found that females preferred the urine of males from different genetic backgrounds, suggesting that female olfactory preferences may be driven by genetic compatibility. Cross-fostering had subtle effects on female olfactory preferences. Although the females showed no preference between the urine odours of adopted and non-adopted males of the other strain, the BALB females preferred the urine odour of BALB males to that of adopted C57 males, whereas the C57 females showed no preference between the urine odour of C57 and adopted BALB males. Using gas chromatography-mass spectrometry (GC-MS) and stepwise discriminant analysis, we found that the ratios of volatile chemicals from urine and preputial gland secretions were altered in the fostered male mice; these changes may have resulted in the behavioural changes observed in the females. Overall, the results suggest that female mice prefer urine odours from males with different genetic backgrounds; this preference may be driven by genetic compatibility. The early maternal environment influences the chemosignals of males and thus may influence the olfactory preferences of

Maternal enrichment affects prenatal hippocampal proliferation and open-field behaviors in female offspring mice.

PubMed

Maruoka, Takashi; Kodomari, Ikuko; Yamauchi, Rena; Wada, Etsuko; Wada, Keiji

2009-04-17

The maternal environment is thought to be important for fetal brain development. However, the effects of maternal environment are not fully understood. Here, we investigated whether enrichment of the maternal environment can influence prenatal brain development and postnatal behaviors in mice. An enriched environment is a housing condition with several objects such as a running wheel, tube and ladder, which are thought to increase sensory, cognitive and motor stimulation in rodents compared with standard housing conditions. First, we measured the number of BrdU-positive cells in the hippocampal dentate gyrus of fetuses from pregnant dams housed in an enriched environment. Our results revealed that maternal enrichment influences cell proliferation in the hippocampus of female, but not male, fetuses. Second, we used the open-field test to investigate postnatal behaviors in the offspring of dams housed in the enriched environment during pregnancy. We found that maternal enrichment significantly affects the locomotor activity and time spent in the center of the open-field in female, but not male, offspring. These results indicate that maternal enrichment influences prenatal brain development and postnatal behaviors in female offspring.

How various drugs affect anxiety-related behavior in male and female rats prenatally exposed to methamphetamine.

PubMed

Macúchová, E; Ševčíková, M; Hrebíčková, I; Nohejlová, K; Šlamberová, R

2016-06-01

Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the

Work–Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress

PubMed Central

Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

2018-01-01

After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work–family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work–family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work–family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women’s perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work–family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work–family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress. PMID:29719522

Work-Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress.

PubMed

Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

2018-01-01

After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work-family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work-family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work-family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women's perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work-family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work-family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress.

Reduction of aberrant NF-κB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice

PubMed Central

Kishi, Noriyuki; MacDonald, Jessica L.; Ye, Julia; Molyneaux, Bradley J.; Azim, Eiman; Macklis, Jeffrey D.

2016-01-01

Mutations in the transcriptional regulator Mecp2 cause the severe X-linked neurodevelopmental disorder Rett syndrome (RTT). In this study, we investigate genes that function downstream of MeCP2 in cerebral cortex circuitry, and identify upregulation of Irak1, a central component of the NF-κB pathway. We show that overexpression of Irak1 mimics the reduced dendritic complexity of Mecp2-null cortical callosal projection neurons (CPN), and that NF-κB signalling is upregulated in the cortex with Mecp2 loss-of-function. Strikingly, we find that genetically reducing NF-κB signalling in Mecp2-null mice not only ameliorates CPN dendritic complexity but also substantially extends their normally shortened lifespan, indicating broader roles for NF-κB signalling in RTT pathogenesis. These results provide new insight into both the fundamental neurobiology of RTT, and potential therapeutic strategies via NF-κB pathway modulation. PMID:26821816

Female Clerical Workers' Occupational Stress: The Role of Person and Social Resources, Negative Affectivity, and Stress Appraisals.

ERIC Educational Resources Information Center

Morris, Jodi E.; Long, Bonita C.

2002-01-01

Relations among person and social resources, work-stress appraisals, and depression were examined with data from 2 longitudinal studies of female clerical workers. Results were consistent with predictions that primary appraisals contribute to change in depression beyond the effects of person and social resources and negative affectivity. There was…

A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome.

PubMed

Christianto, Antonius; Katayama, Syouichi; Kameshita, Isamu; Inazu, Tetsuya

2016-08-01

Rett syndrome (RTT) is a severe X-linked dominant inheritance disorder with a wide spectrum of clinical manifestations. Mutations in Methyl CpG binding protein 2 (MECP2), Cyclin dependent kinase-like 5 (CDKL5) and Forkhead box G1 (FOXG1) have been associated with classic and/or variant RTT. This study was conducted to identify the responsible gene(s) in atypical RTT patient, and to examine the effect of the mutation on protein function. DNA sequence analysis showed a novel heterozygous mutation in CDKL5 identified as c.530A>G which resulted in an amino acid substitution at position 177, from tyrosine to cysteine. Genotyping analysis indicated that the mutation was not merely a single nucleotide polymorphism (SNP). We also revealed that patient's blood lymphocytes had random X-chromosome inactivation (XCI) pattern. Further examination by bioinformatics analysis demonstrated the mutation caused damage or deleterious in its protein. In addition, we demonstrated in vitro kinase assay of mutant protein showed impairment of its activity. Taken together, the results suggested the mutant CDKL5 was responsible for the disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel therapeutic approaches: Rett syndrome and human induced pluripotent stem cell technology

PubMed Central

Gomathi, Mohan

2017-01-01

Recent advances in induced pluripotent stem cell (iPSC) technology target screening and discovering of therapeutic agents for the possible cure of human diseases. Human induced pluripotent stem cells (hiPSC) are the right kind of platform for testing potency of specific active compounds. Ayurveda, the Indian traditional system of medicine developed between 2,500 and 500 BC, is a science involving the intelligent formulations of herbs and minerals. It can serve as a “goldmine” for novel neuroprotective agents used for centuries to treat neurological disorders. This review discusses limitations in screening drugs for neurological disorders and the advantages offered by hiPSC integrated with Indian traditional system of medicine. We begin by describing the current state of hiPSC technology in research on Rett syndrome (RTT) followed by the current controversies in RTT research combined with the emergence of patient-specific hiPSC that indicate an urgent need for researchers to understand the etiology and drug mechanism. We conclude by offering recommendations to reinforce the screening of active compounds present in the ayurvedic medicines using the human induced pluripotent neural model system for research involving drug discovery for RTT. This integrative approach will fill the current knowledge gap in the traditional medicines and drug discovery. PMID:28447035

Oral health in a group of patients with Rett syndrome in the regions of Valencia and Murcia (Spain): A case-control study

PubMed Central

Fuertes-González, María C.

2014-01-01

Objectives: Rett syndrome (RS) is a rare disease with oral manifestations that have not been described in detail or in a standardized manner in the literature. The present study describes the oral health of the population with RS in two Spanish regions, following the protocol of the World Health Organization for conducting common oral health surveys. Study Design: A prospective, observational case-control study was carried out, involving a group of patients with RS (n1=41) and a mean age of 13.37±3.19 years, and an age- and gender-matched control group without RS (n0=82). The data referred to oral health and habits were recorded by means of a questionnaire and oral examination was used to document caries indicators (prevalence of caries, df(t), df(s), DMF(T), DMF(S) and indices referred to dental loss, morbidity, restoration), the Community Periodontal Index (CPI), and the most characteristic oral manifestations. Results: The most frequent oral habit in the patients with RS was diurnal bruxism, followed by stereotyped tongue movements and oral breathing. The caries scores were lower in the RS population than in the control group, but patients with RS showed greater periodontal alterations and a greater prevalence of drooling, dental wear, high-arched palate and anterior open bite. Conclusions: The population with RS exhibits characteristic and early oral habits and alterations, and periodontal problems that are more notorious than caries disease, so that our efforts should focus on the diagnosis and early correction of the parafunctional habits, promoting restorative treatment, and providing instructions on correct oral hygiene. Key words:Rett syndrome, oral habits, bruxism, caries. PMID:25350594

Early exposure to a low dose of bisphenol A affects socio-sexual behavior of juvenile female rats.

PubMed

Porrini, Stefania; Belloni, Virginia; Della Seta, Daniele; Farabollini, Francesca; Giannelli, Giuletta; Dessì-Fulgheri, Francesco

2005-04-15

Play behavior is affected by alteration of the hormonal environment during development. In fact, congenital adrenal hyperplasia or early administration of diethylstilbestrol are able to modify female play behavior in mammals. In this research, play behavior of female rats was used to explore the effects of perinatal exposure to low, environmentally relevant dose of bisphenol A (BPA), a xenoestrogen widely diffused in the environment. We used 18 females born to mothers exposed to 40 microg/kg/day BPA during pregnancy and lactation, and 18 control females. The subjects were observed in a heterosexual social situation from 35 to 55 days of age. Six main behaviors were identified by principal component analysis (PCA): exploration, defensive behavior to males, play behavior with males, play behavior with females, low-intensity mating behavior, social grooming. Early administration of BPA was responsible for a significant increase of exploration (including social investigation) (p<0.001), as well as a decrease of play with males (p<0.02) and social grooming (p<0.01) at 45 days of age, indicating a general decrease of playful interactions. In general our results suggest that BPA does not induce a clear masculinization of female behavior, but is able however to defeminize some aspects of female behavior. This result is compatible with the estrogenic properties of BPA, and suggests caution in the use of a chemical that, in the range of human exposure, is able to influence the development of the brain during a critical period, resulting in long-term effects on behavior.

Screening mosaic F1 females for mutations affecting zebrafish heart induction and patterning.

PubMed

Alexander, J; Stainier, D Y; Yelon, D

1998-01-01

The genetic pathways underlying the induction and anterior-posterior patterning of the heart are poorly understood. The recent emergence of the zebrafish model system now allows a classical genetic approach to such challenging problems in vertebrate development. Two large-scale screens for mutations affecting zebrafish embryonic development have recently been completed; among the hundreds of mutations identified were several that affect specific aspects of cardiac morphogenesis, differentiation, and function. However, very few mutations affecting induction and/or anterior-posterior patterning of the heart were identified. We hypothesize that a directed approach utilizing molecular markers to examine these particular steps of heart development will uncover additional such mutations. To test this hypothesis, we are conducting two parallel screens for mutations that affect either the induction or the anterior-posterior patterning of the zebrafish heart. As an indicator of cardiac induction, we examine expression of nkx2.5, the earliest known marker of precardiac mesoderm; to assess anterior-posterior patterning, we distinguish ventricle from atrium with antibodies that recognize different myosin heavy chain isoforms. In order to expedite the examination of a large number of mutations, we are screening the haploid progeny of mosaic F1 females. In these ongoing screens, we have identified four mutations that affect nkx2.5 expression as well as 21 that disrupt either ventricular or atrial development and thus far have recovered several of these mutations, demonstrating the value of our approach. Future analysis of these and other cardiac mutations will provide further insight into the processes of induction and anterior-posterior patterning of the heart.

Rett-like Severe Encephalopathy Caused by a De Novo GRIN2B Mutation Is Attenuated by D-serine Dietary Supplement.

PubMed

Soto, David; Olivella, Mireia; Grau, Cristina; Armstrong, Judith; Alcon, Clara; Gasull, Xavier; Gómez de Salazar, Macarena; Gratacòs-Batlle, Esther; Ramos-Vicente, David; Fernández-Dueñas, Víctor; Ciruela, Francisco; Bayés, Àlex; Sindreu, Carlos; López-Sala, Anna; García-Cazorla, Àngels; Altafaj, Xavier

2018-01-15

N-Methyl-D-aspartate receptors (NMDARs) play pivotal roles in synaptic development, plasticity, neural survival, and cognition. Despite recent reports describing the genetic association between de novo mutations of NMDAR subunits and severe psychiatric diseases, little is known about their pathogenic mechanisms and potential therapeutic interventions. Here we report a case study of a 4-year-old Rett-like patient with severe encephalopathy carrying a missense de novo mutation in GRIN2B(p.P553T) coding for the GluN2B subunit of NMDAR. We generated a dynamic molecular model of mutant GluN2B-containing NMDARs. We expressed the mutation in cell lines and primary cultures, and we evaluated the putative morphological, electrophysiological, and synaptic plasticity alterations. Finally, we evaluated D-serine administration as a therapeutic strategy and translated it to the clinical practice. Structural molecular modeling predicted a reduced pore size of mutant NMDARs. Electrophysiological recordings confirmed this prediction and also showed gating alterations, a reduced glutamate affinity associated with a strong decrease of NMDA-evoked currents. Moreover, GluN2B(P553T)-expressing neurons showed decreased spine density, concomitant with reduced NMDA-evoked currents and impaired NMDAR-dependent insertion of GluA1 at stimulated synapses. Notably, the naturally occurring coagonist D-serine was able to attenuate hypofunction of GluN2B(p.P553T)-containing NMDARs. Hence, D-serine dietary supplementation was initiated. Importantly, the patient has shown remarkable motor, cognitive, and communication improvements after 17 months of D-serine dietary supplementation. Our data suggest that hypofunctional NMDARs containing GluN2B(p.P553T) can contribute to Rett-like encephalopathy and that their potentiation by D-serine treatment may underlie the associated clinical improvement. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Multigenerational exposure to dietary zearalenone (ZEA), an estrogenic mycotoxin, affects puberty and reproduction in female mice

PubMed Central

Zhao, Fei; Li, Rong; Xiao, Shuo; Honglu, Diao; El Zowalaty, Ahmed E.; Ye, Xiaoqin

2014-01-01

This study investigated potential cumulative effects of multiple pregnancy and multigenerational exposure to dietary ZEA (0, 0.8, 4, or 20 ppm) on female puberty and reproduction in C57BL/6J mice. Multiple pregnancies did not significantly affect litter size or offspring puberty. Significant effects were observed in 20 ppm ZEA-treated females: advanced puberty onset in F0, F1, and F2 generations; decreased implantation rate, pregnancy rate, and litter size, and increased pregnancy gap and gestation period in F1 and F2 generations; and reduced fertility index in F2 generation. F3 females from 0 and 20 ppm groups were split into 0 or 20 ppm ZEA diets at weaning, with advanced puberty onset seen in 0-20 and 20-20 groups and decreased implantation rate observed in 20-20 group. In summary, 20 ppm dietary ZEA advanced puberty onset without obvious cumulative effect and impaired fertility with multigenerational cumulative effect, which could be partially alleviated upon exposure cessation. PMID:24972337

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.

A study of the factors affecting the attitudes of young female students toward chemistry at the high school level

NASA Astrophysics Data System (ADS)

Banya, Santonino K.

Chemistry is a human endeavor that relies on basic human qualities like creativity, insights, reasoning, and skills. It depends on habits of the mind: skepticism, tolerance of ambiguity, openness to new ideas, intellectual honesty, curiosity, and communication. Young female students begin studying chemistry curiosity; however, when unconvinced, they become skeptical. Researches focused on gender studies have indicated that attitudes toward science education differ between males and females. A declining interest in chemistry and the under representation of females in the chemical science was found (Jacobs, 2000). This study investigated whether self-confidence toward chemistry, the influence of role models, and knowledge about the usefulness of chemistry were affecting the attitudes toward chemistry, of 183 high school young females across the United States. The young female students surveyed, had studied chemistry for at least one year prior to participating in the study during the fall semester of 2003. The schools were randomly selected represented diverse economic backgrounds and geographical locations. Data were obtained using Chemistry Attitude Influencing Factors (CAIF) instrument and from interviews with a focus group of three young female students about the effect of self-confidence toward chemistry, the influence of role models, and knowledge about the usefulness of chemistry on their decision to study chemistry. The CAIF instrument consisted of a 12-items self-confidence questionnaire (ConfiS), 12-items each of the influence of role models (RoMoS) and knowledge about usefulness of chemistry (US) questionnaire. ConfiS was adopted (with permission) from CAEQ (Coll & Dalgety, 2001), and both RoMoS and US were modified from TOSRA (Fraser, 1978), public domain document. The three young female students interviewed, gave detailed responses about their opinions regarding self-confidence toward chemistry, the influence of role models, and knowledge about the

Developmental Exposure to Ethinylestradiol Affects Reproductive Physiology, the GnRH Neuroendocrine Network and Behaviors in Female Mouse.

PubMed

Derouiche, Lyes; Keller, Matthieu; Martini, Mariangela; Duittoz, Anne H; Pillon, Delphine

2015-01-01

During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2), the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR) or pharmacological (PHARMACO) doses [0.1 and 1 μg/kg (body weight)/day respectively], from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs.

Exposure to methylphenidate during peri-adolescence affects endocrine functioning and sexual behavior in female Long-Evans rats.

PubMed

Guarraci, Fay A; Holifield, Caroline; Morales-Valenzuela, Jessica; Greene, Kasera; Brown, Jeanette; Lopez, Rebecca; Crandall, Christina; Gibbs, Nicole; Vela, Rebekah; Delgado, Melissa Y; Frohardt, Russell J

2016-03-01

The present study was designed to test the effects of methylphenidate (MPH) exposure on the maturation of endocrine functioning and sexual behavior. Female rat pups received either MPH (2.0mg/kg, i.p.) or saline twice daily between postnatal days 20-35. This period of exposure represents the time just prior to puberty as well as puberty onset. Approximately five weeks after the last injection of MPH or saline, female subjects were hormone-primed and tested during their first sexual experience. Subjects were given the choice to interact with a sexually active male or a sexually receptive female rat (i.e., the partner-preference test). The partner-preference paradigm allows us to assess multiple aspects of female sexual behavior. MPH exposure during peri-adolescence delayed puberty and, when mated for the first time, affected sexual behavior (e.g., increased time spent with the male stimulus and decreased the likelihood of leaving after mounts) during the test of partner preference. When monitoring estrous cyclicity, female subjects treated with MPH during peri-adolescence frequently experienced irregular estrous cycles. The results of the present study suggest that chronic exposure to a therapeutic dose of MPH around the onset of puberty alters long-term endocrine functioning, but with hormone priming, increases sensitivity to sexual stimuli. Copyright © 2015 Elsevier Inc. All rights reserved.

Cell cloning-based transcriptome analysis in Rett patients: relevance to the pathogenesis of Rett syndrome of new human MeCP2 target genes.

PubMed

Nectoux, J; Fichou, Y; Rosas-Vargas, H; Cagnard, N; Bahi-Buisson, N; Nusbaum, P; Letourneur, F; Chelly, J; Bienvenu, T

2010-07-01

More than 90% of Rett syndrome (RTT) patients have heterozygous mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene that encodes the methyl-CpG-binding protein 2, a transcriptional modulator. Because MECP2 is subjected to X chromosome inactivation (XCI), girls with RTT either express the wild-type or mutant allele in each individual cell. To test the consequences of MECP2 mutations resulting from a genome-wide transcriptional dysregulation and to identify its target genes in a system that circumvents the functional mosaicism resulting from XCI, we carried out gene expression profiling of clonal populations derived from fibroblast primary cultures expressing exclusively either the wild-type or the mutant MECP2 allele. Clonal cultures were obtained from skin biopsy of three RTT patients carrying either a non-sense or a frameshift MECP2 mutation. For each patient, gene expression profiles of wild-type and mutant clones were compared by oligonucleotide expression microarray analysis. Firstly, clustering analysis classified the RTT patients according to their genetic background and MECP2 mutation. Secondly, expression profiling by microarray analysis and quantitative RT-PCR indicated four up-regulated genes and five down-regulated genes significantly dysregulated in all our statistical analysis, including excellent potential candidate genes for the understanding of the pathophysiology of this neurodevelopmental disease. Thirdly, chromatin immunoprecipitation analysis confirmed MeCP2 binding to respective CpG islands in three out of four up-regulated candidate genes and sequencing of bisulphite-converted DNA indicated that MeCP2 preferentially binds to methylated-DNA sequences. Most importantly, the finding that at least two of these genes (BMCC1 and RNF182) were shown to be involved in cell survival and/or apoptosis may suggest that impaired MeCP2 function could alter the survival of neurons thus compromising brain function without inducing cell death.

Early-onset seizures due to mosaic exonic deletions of CDKL5 in a male and two females.

PubMed

Bartnik, Magdalena; Derwińska, Katarzyna; Gos, Monika; Obersztyn, Ewa; Kołodziejska, Katarzyna E; Erez, Ayelet; Szpecht-Potocka, Agnieszka; Fang, Ping; Terczyńska, Iwona; Mierzewska, Hanna; Lohr, Naomi J; Bellus, Gary A; Reimschisel, Tyler; Bocian, Ewa; Mazurczak, Tadeusz; Cheung, Sau Wai; Stankiewicz, Paweł

2011-05-01

Mutations in the CDKL5 gene have been associated with an X-linked dominant early infantile epileptic encephalopathy-2. The clinical presentation is usually of severe encephalopathy with refractory seizures and Rett syndrome (RTT)-like phenotype. We attempted to assess the role of mosaic intragenic copy number variation in CDKL5. We have used comparative genomic hybridization with a custom-designed clinical oligonucleotide array targeting exons of selected disease and candidate genes, including CDKL5. We have identified mosaic exonic deletions of CDKL5 in one male and two females with developmental delay and medically intractable seizures. These three mosaic changes represent 60% of all deletions detected in 12,000 patients analyzed by array comparative genomic hybridization and involving the exonic portion of CDKL5. We report the first case of an exonic deletion of CDKL5 in a male and emphasize the importance of underappreciated mosaic exonic copy number variation in patients with early-onset seizures and RTT-like features of both genders.

Affective and Autonomic Responses to Erotic Images: Evidence of Disgust-Based Mechanisms in Female Sexual Interest/Arousal Disorder.

PubMed

DePesa, Natasha S; Cassisi, Jeffrey E

2017-09-01

Disgust has recently been implicated in the development and maintenance of female sexual dysfunction, yet most empirical studies have been conducted with a sexually healthy sample. The current study contributes to the literature by expanding the application of a disgust model of sexual functioning to a clinically relevant sample of women with low sexual desire/arousal and accompanying sexual distress. Young women (mean age = 19.12 years) with psychometrically defined sexual dysfunction (i.e., female sexual interest/arousal disorder [FSIAD] group) and a healthy control group were compared in their affective (i.e., facial electromyography [EMG] and self-report) and autonomic (i.e., heart rate and electrodermal activity) responses to disgusting, erotic, positive, and neutral images. Significant differences were predicted in responses to erotic images only. Specifically, it was hypothesized that the FSIAD group would display affective and autonomic responses consistent with a disgust response, while responses from the control group would align with a general appetitive response. Results largely supported study hypotheses. The FSIAD group displayed significantly greater negative facial affect, reported more subjective disgust, and recorded greater heart rate deceleration than the control group in response to erotic stimuli. Greater subjective disgust response corresponded with more sexual avoidance behavior. Planned follow-up analyses explored correlates of subjective disgust responses.

Neuropeptides affecting the transfer of juvenile hormones from males to females during mating in Spodoptera frugiperda.

PubMed

Hassanien, Intisar T E; Grötzner, Manuela; Meyering-Vos, Martina; Hoffmann, Klaus H

2014-07-01

In the polyandric moth, Spodopterafrugiperda, juvenile hormone (JH) is transferred from the male accessory reproductive glands (AG) to the female bursa copulatrix (BC) during copulation (see Hassanien et al., 2014). Here we used the RNA interference technique to study the role of allatoregulating neuropeptides in controlling the synthesis and transfer of JH during mating. Knockdown of S. frugiperda allatostatin C (Spofr-AS type C) in freshly emerged males leads to an accumulation of JH in the AG beyond that in the control and mating results in a higher transport of JH I and JH II into the female BC. Knockdown of S. frugiperda allatotropin 2 (Spofr-AT2) significantly reduces the amount of JH in the AG as well as its transfer into the female BC during copulation. Knockdown of S. frugiperda allatostatin A (Spofr-AS type A) and S. frugiperda allatotropin (Spofr-AT; Hassanien et al., 2014) only slightly affects the accumulation of JH in the AG and its transfer from the male to the female. We conclude that Spofr-AS type C and Spofr-AT2 act as true allatostatin and true allatotropin, respectively, on the synthesis of JH I and JH II in the male AG. Moreover, both peptides seem to control the synthesis of JH III in the corpora allata of adult males and its release into the hemolymph. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

PubMed

Fournier, Sébastien; Gulemetova, Roumiana; Baldy, Cécile; Joseph, Vincent; Kinkead, Richard

2015-04-01

Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia. Copyright © 2015 the American Physiological Society.

CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

PubMed Central

Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury‐Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

2006-01-01

Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett‐like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto‐temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder

Factors Affecting Drug Abuse in Adolescent Females in Rural Communities

ERIC Educational Resources Information Center

Renes, Susan L.; Strange, Anthony T.

2009-01-01

This article explores factors influencing adolescent female substance use in rural communities. Self-reported data gathered from females 12 to 15 years of age in two northwestern communities in the United States showed an association among gender identity, peer and parental relationships, and substance use. Aggressive masculinity had the strongest…

The anorectic agent, lorcaserin, disturbs estrous cyclicity and produces endometrial hyperplasia without affecting ovarian population in female rats.

PubMed

Abdel-Latif, Raghda T; Zaitone, Sawsan A; Abdel-Mottaleb, Yousra; El-Maraghy, Nabila N

2017-08-15

The present study aims to investigate the effect of the new anorectic agent, lorcaserin, on estrous cyclicity, reproductive hormones and folliculogenesis in female mature rats. Rats were divided into four groups; Group i: control group. Group ii-iv: rats treated with lorcaserin (5, 10 or 30mg/kg/day, p.o.), respectively. The treatment continued for 28days. Lorcaserin (5 or 10mg/kg) caused estrous cycle disturbance in 40% of treated rats while the high dose (30mg/kg) produced disturbances in 100% of the treated rats. Lorcaserin (5-30mg/kg) altered some of female hormones where it enhanced estradiol but reduced luteinizing hormone. Minimal edema with congested vessels was observed in the medulla of ovarian sections. Further, epithelial and uterine sections showed hyperplasia. Taken together, the present results demonstrated that lorcaserin affected some reproductive hormones, disturbed estrous cyclicity and induced histopathological changes in the ovaries and uteri without affecting the ovarian populations. Therefore, lorcaserin should be used with caution in women of child bearing potential until adequate clinical safety data are available. Copyright © 2017 Elsevier Inc. All rights reserved.

How Culture Affects Female Inequality across Countries: An Empirical Study

ERIC Educational Resources Information Center

Cheung, Hoi Yan; Chan, Alex W. H.

2007-01-01

Many studies have commented that culture has an influence on gender inequality. However, few studies have provided data that could be used to investigate how culture actually influences female inequality. One of the aims of this study is to investigate whether Hofstede's cultural dimensions have an impact on female inequality in education in terms…

Male sexual harassment alters female social behaviour towards other females.

PubMed

Darden, Safi K; Watts, Lauren

2012-04-23

Male harassment of females to gain mating opportunities is a consequence of an evolutionary conflict of interest between the sexes over reproduction and is common among sexually reproducing species. Male Trinidadian guppies Poecilia reticulata spend a large proportion of their time harassing females for copulations and their presence in female social groups has been shown to disrupt female-female social networks and the propensity for females to develop social recognition based on familiarity. In this study, we investigate the behavioural mechanisms that may lead to this disruption of female sociality. Using two experiments, we test the hypothesis that male presence will directly affect social behaviours expressed by females towards other females in the population. In experiment one, we tested for an effect of male presence on female shoaling behaviour and found that, in the presence of a free-swimming male guppy, females spent shorter amounts of time with other females than when in the presence of a free-swimming female guppy. In experiment two, we tested for an effect of male presence on the incidence of aggressive behaviour among female guppies. When males were present in a shoal, females exhibited increased levels of overall aggression towards other females compared with female only shoals. Our work provides direct evidence that the presence of sexually harassing males alters female-female social behaviour, an effect that we expect will be recurrent across taxonomic groups.

An investigation of factors affecting elementary female student teachers' choice of science as a major at college level in Zimbabwe

NASA Astrophysics Data System (ADS)

Mlenga, Francis Howard

The purpose of the study was to determine factors affecting elementary female student teachers' choice of science as a major at college level in Zimbabwe. The study was conducted at one of the Primary School Teachers' Colleges in Zimbabwe. A sample of two hundred and thirty-eight female student teachers was used in the study. Of these one hundred and forty-two were non-science majors who had been randomly selected, forty-one were science majors and forty-five were math majors. Both science and math majors were a convenient sample because the total enrollment of the two groups was small. All the subjects completed a survey questionnaire that had sixty-eight items. Ten students from the non-science majors were selected for individual interviews and the same was done for the science majors. A further eighteen were selected from the non-science majors and divided into three groups of six each for focus group interviews. The same was done for the science majors. The interviews were audio taped and transcribed. Data from the survey questionnaires were analyzed using Binary Logistic Regression which predicted factors that affected students' choice of science as a major. The transcribed interview data were analyzed used using domain, taxonomic and componential analyses. Results of the study indicated that elementary female students' choice of science as a major at college level is affected by students' attitudes toward science, teacher behavior, out-of-school experiences, role models, gender stereotyping, parental influence, peer influence, in-school experiences, and societal expectations, namely cultural and social expectations.

mGlu5 positive allosteric modulation normalizes synaptic plasticity defects and motor phenotypes in a mouse model of Rett syndrome

PubMed Central

Gogliotti, Rocco G.; Senter, Rebecca K.; Rook, Jerri M.; Ghoshal, Ayan; Zamorano, Rocio; Malosh, Chrysa; Stauffer, Shaun R.; Bridges, Thomas M.; Bartolome, Jose M.; Daniels, J. Scott; Jones, Carrie K.; Lindsley, Craig W.; Conn, P. Jeffrey; Niswender, Colleen M.

2016-01-01

Rett syndrome (RS) is a neurodevelopmental disorder that shares many symptomatic and pathological commonalities with idiopathic autism. Alterations in protein synthesis-dependent synaptic plasticity (PSDSP) are a hallmark of a number of syndromic forms of autism; in the present work, we explore the consequences of disruption and rescue of PSDSP in a mouse model of RS. We report that expression of a key regulator of synaptic protein synthesis, the metabotropic glutamate receptor 5 (mGlu5) protein, is significantly reduced in both the brains of RS model mice and in the motor cortex of human RS autopsy samples. Furthermore, we demonstrate that reduced mGlu5 expression correlates with attenuated DHPG-induced long-term depression in the hippocampus of RS model mice, and that administration of a novel mGlu5 positive allosteric modulator (PAM), termed VU0462807, can rescue synaptic plasticity defects. Additionally, treatment of Mecp2-deficient mice with VU0462807 improves motor performance (open-field behavior and gait dynamics), corrects repetitive clasping behavior, as well as normalizes cued fear-conditioning defects. Importantly, due to the rationale drug discovery approach used in its development, our novel mGlu5 PAM improves RS phenotypes and synaptic plasticity defects without evoking the overt adverse effects commonly associated with potentiation of mGlu5 signaling (i.e. seizures), or affecting cardiorespiratory defects in RS model mice. These findings provide strong support for the continued development of mGlu5 PAMs as potential therapeutic agents for use in RS, and, more broadly, for utility in idiopathic autism. PMID:26936821

Medial prefrontal cortex lesions in the female rat affect sexual and maternal behavior and their sequential organization.

PubMed

Afonso, Veronica M; Sison, Margarette; Lovic, Vedran; Fleming, Alison S

2007-06-01

Temporal sequences of sexual and maternal behaviors in female rats and their correlation with each other and with performance on a sensory-motor gating response inhibition task assessed by prepulse inhibition (PPI) were investigated following medial prefrontal cortex (mPFC) lesions. Following excitotoxic mPFC (n = 10) or sham (n = 9) lesions, sexual behaviors across the ovarian cycle were scored. After mating and parturition, maternal interactions were scored until pups reached postnatal Day 10. After resumption of the ovarian cycle, the female rats were tested for PPI. Compared with sham lesions, mPFC lesions impaired proceptive behaviors and some maternal behaviors (e.g., pup retrieval, pup licking) but did not affect others (e.g., nest building, pup mouthing). Lesions disrupted temporal sequences of solicitations (number of male orientations followed, within 4 s, by a level change) and pup retrievals (number of pup retrievals followed, within 5 s, by another retrieval). These sequential behavior patterns were significantly correlated with each other and with PPI. However, when PPI effects were partialled out, group differences were less strong, but persisted. This study demonstrated that mPFC manipulations affect actions rich in sequential structure in response to biologically relevant stimuli. Copyright (c) 2007 APA, all rights reserved.

Activity and social factors affect cohesion among individuals in female Japanese macaques: A simultaneous focal-follow study.

PubMed

Nishikawa, Mari; Suzuki, Mariko; Sprague, David S

2014-07-01

Understanding cohesion among individuals within a group is necessary to reveal the social system of group-living primates. Japanese macaques (Macaca fuscata) are female-philopatric primates that reside in social groups. We investigated whether individual activity and social factors can affect spatio-temporal cohesion in wild female Japanese macaques. We conducted behavioral observation on a group, which contained 38 individuals and ranged over ca. 60 ha during the study period. Two observers carried out simultaneous focal-animal sampling of adult female pairs during full-day follows using global positioning system which enabled us to quantify interindividual distances (IIDs), group members within visual range (i.e., visual unit), and separation duration beyond visual range as indicators of cohesion among individuals. We found considerable variation in spatio-temporal group cohesion. The overall mean IID was 99.9 m (range = 0-618.2 m). The percentage of IIDs within visual range was 23.1%, within auditory range was 59.8%, and beyond auditory range was 17.1%. IIDs varied with activity; they were shorter during grooming and resting, and longer during foraging and traveling. Low-ranking females showed less cohesion than high-ranking ones. Kin females stayed nearly always within audible range. The macaques were weakly cohesive with small mean visual unit size (3.15 counting only adults, 5.99 counting all individuals). Both-sex units were the most frequently observed visual unit type when they were grooming/resting. Conversely, female units were the most frequently observed visual unit type when they were foraging. The overall mean visual separation duration was 25.7 min (range = 3-513 min). Separation duration was associated with dominance rank. These results suggest that Japanese macaques regulate cohesion among individuals depending on their activity and on social relationships; they were separated to adapt food distribution and aggregated to maintain social

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

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances affects leukocyte telomere length in female newborns.

PubMed

Liu, Han; Chen, Qian; Lei, Lei; Zhou, Wei; Huang, Lisu; Zhang, Jun; Chen, Dan

2018-04-01

Evidence has shown that leukocyte telomere length (LTL) at birth is related to the susceptibility to various diseases in later life and the setting of newborn LTL is influenced by the intrauterine environment. Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a kind of persistent organic pollutants, are commonly used in commercial and domestic applications and are capable of crossing the maternal-fetal barrier during pregnancy. We hypothesized that intrauterine exposure to PFASs may affect fetal LTL by increasing oxidative stress. To verify this hypothesis, LTL, concentrations of PFASs and reactive oxygen species (ROS) were measured in umbilical cord blood of 581 newborns from a prospective cohort. Our results showed that there were interactions between PFOS/PFDA and sex on LTL and ROS. The LTL was significantly shorter (0.926 ± 0.053 vs 0.945 ± 0.054, P = .023 for PFOS; 0.919 ± 0.063 vs 0.940 ± 0.059, P = .011 for PFDA) and the ROS levels were extremely higher (252.9 ± 60.5 [M] vs 233.5 ± 53.6 [M], P = .031 for PFOS; 255.2 ± 62.9 [M] vs 232.9 ± 58.3 [M], P = .011 for PFDA) in the female newborns whose PFOS or PFDA concentrations fell in the upmost quartile compared with those in the lowest quartile after adjusting for potential confounders. ROS levels were inversely associated with LTL in female newborns (β = -1.42 × 10 -4 , P = .022). 13% of the effect of PFOS on female LTL was mediated through ROS approximately by the mediation analyses. However, in male newborns, no relationships among PFASs, ROS and LTL were observed. Our findings suggest a "programming" role of PFASs on fetal telomere biology system in females in intrauterine stage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rett Syndrome Mutation MeCP2 T158A Disrupts DNA Binding, Protein Stability and ERP Responses

PubMed Central

Goffin, Darren; Allen, Megan; Zhang, Le; Amorim, Maria; Wang, I-Ting Judy; Reyes, Arith-Ruth S.; Mercado-Berton, Amy; Ong, Caroline; Cohen, Sonia; Hu, Linda; Blendy, Julie A.; Carlson, Gregory C.; Siegel, Steve J.; Greenberg, Michael E.; Zhou, Zhaolan (Joe)

2011-01-01

Mutations in the MECP2 gene cause the autism spectrum disorder Rett Syndrome (RTT). One of the most common mutations associated with RTT occurs at MeCP2 Threonine 158 converting it to Methionine (T158M) or Alanine (T158A). To understand the role of T158 mutation in the pathogenesis of RTT, we generated knockin mice recapitulating MeCP2 T158A mutation. Here we show a causal role for T158A mutation in the development of RTT-like phenotypes including developmental regression, motor dysfunction, and learning and memory deficits. These phenotypes resemble those in Mecp2-null mice and manifest through a reduction in MeCP2 binding to methylated DNA and a decrease in MeCP2 protein stability. Importantly, the age-dependent development of event-related neuronal responses are disrupted by MeCP2 mutation, suggesting that impaired neuronal circuitry underlies the pathogenesis of RTT and that assessment of event-related potentials may serve as a biomarker for RTT and treatment evaluation. PMID:22119903

Institutional Factors That Affect the Mathematical Achievement of African American Females

ERIC Educational Resources Information Center

Chatman, Audrey

2011-01-01

This dissertation explored how institutional factors impact the mathematical achievement of African American middle school females. The purpose of the research was to provide insight into African American females' perception of their mathematics experiences and demonstrate how both internal and external factors contribute to their achievement.…

Cognitive training modifies frequency EEG bands and neuropsychological measures in Rett syndrome.

PubMed

Fabio, Rosa Angela; Billeci, Lucia; Crifaci, Giulia; Troise, Emilia; Tortorella, Gaetano; Pioggia, Giovanni

2016-01-01

Rett syndrome (RS) is a childhood neurodevelopmental disorder characterized by a primary disturbance in neuronal development. Neurological abnormalities in RS are reflected in several behavioral and cognitive impairments such as stereotypies, loss of speech and hand skills, gait apraxia, irregular breathing with hyperventilation while awake, and frequent seizures. Cognitive training can enhance both neuropsychological and neurophysiological parameters. The aim of this study was to investigate whether behaviors and brain activity were modified by training in RS. The modifications were assessed in two phases: (a) after a short-term training (STT) session, i.e., after 30 min of training and (b) after long-term training (LTT), i.e., after 5 days of training. Thirty-four girls with RS were divided into two groups: a training group (21 girls) who underwent the LTT and a control group (13 girls) that did not undergo LTT. The gaze and quantitative EEG (QEEG) data were recorded during the administration of the tasks. A gold-standard eye-tracker and a wearable EEG equipment were used. Results suggest that the participants in the STT task showed a habituation effect, decreased beta activity and increased right asymmetry. The participants in the LTT task looked faster and longer at the target, and show increased beta activity and decreased theta activity, while a leftward asymmetry was re-established. The overall result of this study indicates a positive effect of long-term cognitive training on brain and behavioral parameters in subject with RS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevalence and Factors Affecting Dysmenorrhea in Female University Students: Effect on General Comfort Level.

PubMed

Aktaş, Demet

2015-08-01

The purpose of this study was to investigate the prevalence and the affecting factors of dysmenorrhea and its effects on overall comfort among female university students. This was a cross-sectional study. The research was carried out between October and November 2013 at a university in Ankara. This study was conducted with 200 female students. The data were analyzed using frequencies, means, SD, χ(2) tests, independent t tests and analysis of variance. Data were collected using an interview questionnaire, the visual analog scale (VAS) and the General Comfort Questionnaire. The mean age of students in this study group was 20.85 ± 2.15 years. The prevalence of dysmenorrhea in the students was 84%. The mean severity of pain was 5.78 ± 2.45 on the VAS. The present study found that 45.8% of female students experienced moderate menstrual pain and the most common co-occurring symptoms were irritability (34.6%) and fatigue (21.5%). One-fourth of the students with dysmenorrhea consulted the advice of a physician and the most commonly used methods for pain were analgesics (69%), heat application (56.5%), and rest (71.4%). Family history of dysmenorrhea, education about menstruation, and frequency of menstrual cycle were identified as important factors in the development of dysmenorrhea (p < .05). The mean general comfort score for students with dysmenorrhea (2.57 ± 0.25) was lower than that of students without the condition (2.65 ± 0.23). Also, use of the methods for management of dysmenorrhea was found to increase students' general comfort levels. Therefore, it is important for nurses to educate and advise adolescents and young women about dysmenorrhea. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Factors Affecting the Unemployment (Rate) of Female Art Graduates in Iran

ERIC Educational Resources Information Center

Hedayat, Mina; Kahn, Sabzali Musa; Hanafi, Jaffri

2013-01-01

The aim of this study is to explore the relationship between the opportunities of female artist graduates in Tehran Province and the current employment market. Mixed method was employed in this study. The population of the current study consisted of 240 female artist graduates selected using a systematic random sampling method from both public and…

What does the nature of the MECP2 mutation tell us about parental origin and recurrence risk in Rett syndrome?

PubMed

Zhang, J; Bao, X; Cao, G; Jiang, S; Zhu, X; Lu, H; Jia, L; Pan, H; Fehr, S; Davis, M; Leonard, H; Ravine, D; Wu, X

2012-12-01

The MECP2 mutations occurring in the severe neurological disorder Rett syndrome are predominantly de novo, with rare familial cases. The aims of this study were to provide a precise estimate of the parental origin of MECP2 mutations using a large Chinese sample and to assess whether parental origin varied by mutation type. The parental origin was paternal in 84/88 [95.5%, (95% confidence interval 88.77-98.75)] of sporadic Chinese cases. However, in a pooled sample including data from the literature the spectrum of mutations occurring on maternally and paternally derived chromosomes differed significantly. The excess we found of 'single base pair gains or losses' on maternally derived MECP2 gene alleles suggests that this mutational category is associated with an elevated risk of gonadal mosaicism, which has implications for genetic counseling. © 2011 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Inflammatory protein response in CDKL5-Rett syndrome: evidence of a subclinical smouldering inflammation.

PubMed

Cortelazzo, Alessio; de Felice, Claudio; Leoncini, Silvia; Signorini, Cinzia; Guerranti, Roberto; Leoncini, Roberto; Armini, Alessandro; Bini, Luca; Ciccoli, Lucia; Hayek, Joussef

2017-03-01

Mutations in the cyclin-dependent kinase-like 5 gene cause a clinical variant of Rett syndrome (CDKL5-RTT). A role for the acute-phase response (APR) is emerging in typical RTT caused by methyl-CpG-binding protein 2 gene mutations (MECP2-RTT). No information is, to date, available on the inflammatory protein response in CDKL5-RTT. We evaluated, for the first time, the APR protein response in CDKL5-RTT. Protein patterns in albumin- and IgG-depleted plasma proteome from CDKL5-RTT patients were evaluated by two-dimensional gel electrophoresis/mass spectrometry. The resulting data were related to circulating cytokines and compared to healthy controls or MECP2-RTT patients. The effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) were evaluated. CDKL5-RTT mutations resulted in a subclinical attenuated inflammation, specifically characterized by an overexpression of the complement component C3 and CD5 antigen-like, both strictly related to the inflammatory response. Cytokine dysregulation featuring a bulk increase of anti-inflammatory cytokines, predominantly IL-10, could explain the unchanged erythrocyte sedimentation rate and atypical features of inflammation in CDKL5-RTT. Omega-3 PUFAs were able to counterbalance the pro-inflammatory status. For the first time, we revealed a subclinical smouldering inflammation pattern in CDKL5-RTT consisting in the coexistence of an atypical APR coupled with a dysregulated cytokine response.

Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in Females With Major Affective Disorders

PubMed Central

Ji, Baohu; Higa, Kerin K.; Kelsoe, John R.; Zhou, Xianjin

2015-01-01

suggest that XIST and KDM5C expression could be used as a biological marker for diagnosis of psychiatric disorders in a significantly large subset of female patients. Research in context Due to lack of biological markers, diagnosis and treatment of psychiatric disorders are subjective. There is utmost urgency to identify biomarkers for clinics, research, and drug development. We found that XIST and KDM5C gene expression may be used as a biological marker for diagnosis of major affective disorders in a significantly large subset of female patients from the general population. Our studies show that over-expression of XIST and some X-linked escapee genes may be a common mechanism for development of psychiatric disorders between the patients with rare genetic diseases (XXY or XXX) and the general population of female psychiatric patients. PMID:26425698

Factors affecting fecal glucocorticoid levels in semi-free-ranging female mandrills (Mandrillus sphinx).

PubMed

Setchell, Joanna M; Smith, Tessa; Wickings, E Jean; Knapp, Leslie A

2008-11-01

Subordinate female cercopithecine primates often experience decreased reproductive success in comparison with high-ranking females, with a later age at sexual maturity and first reproduction and/or longer interbirth intervals. One explanation that has traditionally been advanced to explain this is high levels of chronic social stress in subordinates, resulting from agonistic and aggressive interactions and leading to higher basal levels of glucocorticoids. We assessed the relationships among fecal cortisol levels and reproductive condition, dominance rank, degree of social support, and fertility in female mandrills (Mandrillus sphinx) living in a semi-free-ranging colony in Franceville, Gabon. Lower-ranking females in this colony have a reproductive disadvantage relative to higher-ranking females, and we were interested in determining whether this relationship between dominance rank and reproductive success is mediated through stress hormones. We analyzed 340 fecal samples from 19 females, collected over a 14-month period. We found that pregnant females experienced higher fecal cortisol levels than cycling or lactating females. This is similar to results for other primate species and is likely owing to increased metabolic demands and interactions between the hypothalamus-pituitary-adrenal axis, estrogen, and placental production of corticotrophin releasing hormones during pregnancy. There was no influence of dominance rank on fecal cortisol levels, suggesting that subordinate females do not suffer chronic stress. This may be because female mandrills have a stable social hierarchy, with low levels of aggression and high social support. However, we found no relationship between matriline size, as a measure of social support, and fecal cortisol levels. Subordinates may be able to avoid aggression from dominants in the large enclosure or may react only transiently to specific aggressive events, rather than continuously expecting them. Finally, we found no relationship

Substrate texture affects female cricket walking response to male calling song

NASA Astrophysics Data System (ADS)

Sarmiento-Ponce, E. J.; Sutcliffe, M. P. F.; Hedwig, B.

2018-03-01

Field crickets are extensively used as a model organism to study female phonotactic walking behaviour, i.e. their attraction to the male calling song. Laboratory-based phonotaxis experiments generally rely on arena or trackball-based settings; however, no attention has been paid to the effect of substrate texture on the response. Here, we tested phonotaxis in female Gryllus bimaculatus, walking on trackballs machined from methyl-methacrylate foam with different cell sizes. Surface height variations of the trackballs, due to the cellular composition of the material, were measured with profilometry and characterized as smooth, medium or rough, with roughness amplitudes of 7.3, 16 and 180 µm. Female phonotaxis was best on a rough and medium trackball surface, a smooth surface resulted in a significant lower phonotactic response. Claws of the cricket foot were crucial for effective walking. Females insert their claws into the surface pores to allow mechanical interlocking with the substrate texture and a high degree of attachment, which cannot be established on smooth surfaces. These findings provide insight to the biomechanical basis of insect walking and may inform behavioural studies that the surface texture on which walking insects are tested is crucial for the resulting behavioural response.

The role of sexual preferences in intrasexual female competition

PubMed Central

2012-01-01

Background While search costs have long been understood to affect the evolution of female preference, other costs associated with mating have been the focus of much less attention. Here I consider a novel mate choice cost: female-female intrasexual competition, that is, when females compete with each other for mates. This competition results in cost to female fecundity, such as a reduction in fertility due to decreased direct benefits, sperm limitation, or time and resources spent competing for a mate. I asked if female-female competition affects the evolution of preferences, and further, if the presence of multiple, different, preferences in a population can reduce competitive costs. Results Using population genetic models of preference and trait evolution, I found that intrasexual competition leads to direct selection against female preferences, and restricts the parameter space under which preference may evolve. I also examined how multiple, different, preferences affected preference evolution with female intrasexual competition. Conclusions Multiple preferences primarily serve to increase competitive costs and decrease the range of parameters under which preferences may evolve. PMID:23148567

Female sexuality

PubMed Central

Rao, T.S. Sathyanarana; Nagaraj, Anil Kumar M.

2015-01-01

Sex is a motive force bringing a man and a woman into intimate contact. Sexuality is a central aspect of being human throughout life and encompasses sex, gender identities and roles, sexual orientation, eroticism, pleasure, intimacy, and reproduction. Sexuality is experienced and expressed in thoughts, fantasies, desires, beliefs, attitudes, values, behaviors, practices, roles and relationships. Though generally, women are sexually active during adolescence, they reach their peak orgasmic frequency in their 30 s, and have a constant level of sexual capacity up to the age of 55 with little evidence that aging affects it in later life. Desire, arousal, and orgasm are the three principle stages of the sexual response cycle. Each stage is associated with unique physiological changes. Females are commonly affected by various disorders in relation to this sexual response cycle. The prevalence is generally as high as 35–40%. There are a wide range of etiological factors like age, relationship with a partner, psychiatric and medical disorders, psychotropic and other medication. Counseling to overcome stigma and enhance awareness on sexuality is an essential step in management. There are several effective psychological and pharmacological therapeutic approaches to treat female sexual disorders. This article is a review of female sexuality. PMID:26330647

Treatment of cardiac arrhythmias in a mouse model of Rett syndrome with Na+-channel-blocking antiepileptic drugs

PubMed Central

Herrera, José A.; Ward, Christopher S.; Pitcher, Meagan R.; Percy, Alan K.; Skinner, Steven; Kaufmann, Walter E.; Glaze, Daniel G.; Wehrens, Xander H. T.; Neul, Jeffrey L.

2015-01-01

One quarter of deaths associated with Rett syndrome (RTT), an X-linked neurodevelopmental disorder, are sudden and unexpected. RTT is associated with prolonged QTc interval (LQT), and LQT-associated cardiac arrhythmias are a potential cause of unexpected death. The standard of care for LQT in RTT is treatment with β-adrenergic antagonists; however, recent work indicates that acute treatment of mice with RTT with a β-antagonist, propranolol, does not prevent lethal arrhythmias. In contrast, acute treatment with the Na+ channel blocker phenytoin prevented arrhythmias. Chronic dosing of propranolol may be required for efficacy; therefore, we tested the efficacy of chronic treatment with either propranolol or phenytoin on RTT mice. Phenytoin completely abolished arrhythmias, whereas propranolol showed no benefit. Surprisingly, phenytoin also normalized weight and activity, but worsened breathing patterns. To explore the role of Na+ channel blockers on QT in people with RTT, we performed a retrospective analysis of QT status before and after Na+ channel blocker antiepileptic therapies. Individuals with RTT and LQT significantly improved their QT interval status after being started on Na+ channel blocker antiepileptic therapies. Thus, Na+ channel blockers should be considered for the clinical management of LQT in individuals with RTT. PMID:25713300

Factors affecting female space use in ten populations of prairie chickens

USGS Publications Warehouse

Winder, Virginia L.; Carrlson, Kaylan M.; Gregory, Andrew J.; Hagen, Christian A.; Haukos, David A.; Kesler, Dylan C.; Larsson, Lena C.; Matthews, Ty W.; McNew, Lance B.; Patten, Michael; Pitman, Jim C.; Powell, Larkin A.; Smith, Jennifer A.; Thompson, Tom; Wolfe, Donald H.; Sandercock, Brett K.

2015-01-01

Conservation of wildlife depends on an understanding of the interactions between animal movements and key landscape factors. Habitat requirements of wide-ranging species often vary spatially, but quantitative assessment of variation among replicated studies at multiple sites is rare. We investigated patterns of space use for 10 populations of two closely related species of prairie grouse: Greater Prairie-Chickens (Tympanuchus cupido) and Lesser Prairie-Chickens (T. pallidicinctus). Prairie chickens require large, intact tracts of native grasslands, and are umbrella species for conservation of prairie ecosystems in North America. We used resource utilization functions to investigate space use by female prairie chickens during the 6-month breeding season from March through August in relation to lek sites, habitat conditions, and anthropogenic development. Our analysis included data from 382 radio-marked individuals across a major portion of the extant range. Our project is a unique opportunity to study comparative space use of prairie chickens, and we employed standardized methods that facilitated direct comparisons across an ecological gradient of study sites. Median home range size of females varied ~10-fold across 10 sites (3.6–36.7 km2), and home ranges tended to be larger at sites with higher annual precipitation. Proximity to lek sites was a strong and consistent predictor of space use for female prairie chickens at all 10 sites. The relative importance of other predictors of space use varied among sites, indicating that generalized habitat management guidelines may not be appropriate for these two species. Prairie chickens actively selected for prairie habitats, even at sites where ~90% of the land cover within the study area was prairie. A majority of the females monitored in our study (>95%) had activity centers within 5 km of leks, suggesting that conservation efforts can be effectively concentrated near active lek sites. Our data on female space use

Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.

PubMed

Lefèvre, Pavine L C; Berger, Robert G; Ernest, Sheila R; Gaertner, Dean W; Rawn, Dorothea F K; Wade, Michael G; Robaire, Bernard; Hales, Barbara F

2016-01-01

Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis. © 2016 by the Society for the Study of Reproduction, Inc.

Stereotypical hand movements in 144 subjects with Rett syndrome from the population-based Australian database.

PubMed

Carter, Philippa; Downs, Jenny; Bebbington, Ami; Williams, Simon; Jacoby, Peter; Kaufmann, Walter E; Leonard, Helen

2010-02-15

Stereotypic hand movements are a feature of Rett Syndrome but few studies have observed their nature systematically. Video data in familiar settings were obtained on subjects (n = 144) identified from an Australian population-based database. Hand stereotypies were demonstrated by most subjects (94.4%), 15 categories were observed and midline wringing was seen in approximately 60% of subjects. There was a median of two stereotypies per subject but this number decreased with age. Clapping and mouthing of hands were more prevalent in girls younger than 8 years and wringing was more prevalent in women 19 years or older. Clapping was commoner in those with p.R306C and early truncating mutations, and much rarer in those with p.R106W, p.R270X, p.R168X, and p.R255X. Stereotypies tended to be less frequent in those with more severe mutations. Otherwise, there were no clear relationships between our categories of stereotypies and mutation. Approximately a quarter each had predominantly right and left handed stereotypies and for the remaining half, no clear laterality was seen. Results were similar for all cases and when restricted to those with a pathogenic mutation. Hand stereotypies changed with increasing age but limited relationships with MECP2 mutations were identified. (c) 2009 Movement Disorder Society.

Floral function: effects of traits on pollinators, male and female pollination success, and female fitness across three species of milkweeds (Asclepias).

PubMed

La Rosa, Raffica J; Conner, Jeffrey K

2017-01-01

Central questions in plant reproductive ecology are whether the functions of floral traits in hermaphrodites create conflict between sexes that could slow evolution, and whether individual floral traits function in pollinator attraction, efficiency, or both. We studied how floral traits affect pollinator visitation and efficiency, and how they affect male and female function and female fitness within and across three Asclepias species that differ in floral morphology. Using separate multiple regressions, we regressed pollen removal, deposition, and fruit number onto six floral traits. We also used path analyses integrating these variables with pollinator visitation data for two of the species to further explore floral function and its effects on fruit production. Most traits affected male pollination success only, and these effects often differed between species. The exception was increased slit length, which increased pollinia insertion in two of the species. There were no interspecific differences in the effects of the traits on female pollination success. All traits except horn reach affected pollination efficiency in at least one species, and horn reach and two hood dimensions were the only traits to affect pollinator attraction, but in just one species. Traits tended to function in only one sex, and more traits affected function through pollinator efficiency than through attraction. There was no significant link between female pollination success and female fitness in any of the three species; this pattern is consistent with fruit production not being limited by pollen deposition. © 2017 Botanical Society of America.

Female pattern hair loss.

PubMed

Ioannides, Dimitrios; Lazaridou, Elizabeth

2015-01-01

Female pattern hair loss, or female pattern androgenetic alopecia, is a nonscarring alopecia with a multi-factorial etiology that mostly affects postmenopausal women and is characterized by a reduction in hair density over the crown and frontal scalp. The clinical picture is characterized by a diffuse rarefaction of scalp hair over the mid-frontal scalp and a more-or-less intact frontal hairline without any signs of inflammation or scarring. Although the disease poses only a cosmetic concern, it is chronic and may have a significant negative psychological impact on the affected person. The aim of treating female pattern hair loss is to reduce hair loss and, to a certain extent, succeed in promoting hair regrowth. Various treatment methods are available, but it remains unclear which are the most effective. Early initiation of treatment and the combination of various modalities seem to be more efficacious than monotherapy. © 2015 S. Karger AG, Basel.

Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis1

PubMed Central

Lefèvre, Pavine L.C.; Berger, Robert G.; Ernest, Sheila R.; Gaertner, Dean W.; Rawn, Dorothea F.K.; Wade, Michael G.; Robaire, Bernard; Hales, Barbara F.

2015-01-01

Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis. PMID:26607716

Associations between attention, affect and cardiac activity in a single yoga session for female cancer survivors: an enactive neurophenomenology-based approach.

PubMed

Mackenzie, Michael J; Carlson, Linda E; Paskevich, David M; Ekkekakis, Panteleimon; Wurz, Amanda J; Wytsma, Kathryn; Krenz, Katie A; McAuley, Edward; Culos-Reed, S Nicole

2014-07-01

Yoga practice is reported to lead to improvements in quality of life, psychological functioning, and symptom indices in cancer survivors. Importantly, meditative states experienced within yoga practice are correlated to neurophysiological systems that moderate both focus of attention and affective valence. The current study used a mixed methods approach based in neurophenomenology to investigate associations between attention, affect, and cardiac activity during a single yoga session for female cancer survivors. Yoga practice was associated with a linear increase in associative attention and positive affective valence, while shifts in cardiac activity were related to the intensity of each yoga sequence. Changes in attention and affect were predicted by concurrently assessed cardiac activity. Awareness of breathing, physical movement, and increased relaxation were reported by participants as potential mechanisms for yoga's salutary effects. While yoga practice shares commonalities with exercise and relaxation training, yoga may serve primarily as a promising meditative attention-affect regulation training methodology. Copyright © 2014 Elsevier Inc. All rights reserved.

Inbreeding affects sexual signalling in males but not females of Tenebrio molitor.

PubMed

Pölkki, Mari; Krams, Indrikis; Kangassalo, Katariina; Rantala, Markus J

2012-06-23

In many species of animals, individuals advertise their quality with sexual signals to obtain mates. Chemical signals such as volatile pheromones are species specific, and their primary purpose is to influence mate choice by carrying information about the phenotypic and genetic quality of the sender. The deleterious effects of consanguineous mating on individual quality are generally known, whereas the effect of inbreeding on sexual signalling is poorly understood. Here, we tested whether inbreeding reduces the attractiveness of sexual signalling in the mealworm beetle, Tenebrio molitor, by testing the preferences for odours of inbred and outbred (control) individuals of the opposite sex. Females were more attracted to the odours produced by outbred males than the odours produced by inbred males, suggesting that inbreeding reduces the attractiveness of male sexual signalling. However, we did not find any difference between the attractiveness of inbred and outbred female odours, which may indicate that the quality of females is either irrelevant for T. molitor males or quality is not revealed through female odours.

Inbreeding affects sexual signalling in males but not females of Tenebrio molitor

PubMed Central

Pölkki, Mari; Krams, Indrikis; Kangassalo, Katariina; Rantala, Markus J.

2012-01-01

In many species of animals, individuals advertise their quality with sexual signals to obtain mates. Chemical signals such as volatile pheromones are species specific, and their primary purpose is to influence mate choice by carrying information about the phenotypic and genetic quality of the sender. The deleterious effects of consanguineous mating on individual quality are generally known, whereas the effect of inbreeding on sexual signalling is poorly understood. Here, we tested whether inbreeding reduces the attractiveness of sexual signalling in the mealworm beetle, Tenebrio molitor, by testing the preferences for odours of inbred and outbred (control) individuals of the opposite sex. Females were more attracted to the odours produced by outbred males than the odours produced by inbred males, suggesting that inbreeding reduces the attractiveness of male sexual signalling. However, we did not find any difference between the attractiveness of inbred and outbred female odours, which may indicate that the quality of females is either irrelevant for T. molitor males or quality is not revealed through female odours. PMID:22237501

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.

Ovarian fluid of receptive females enhances sperm velocity

NASA Astrophysics Data System (ADS)

Gasparini, Clelia; Andreatta, Gabriele; Pilastro, Andrea

2012-05-01

The females of several internal fertilizers are able to store sperm for a long time, reducing the risk of sperm limitation. However, it also means that males can attempt to mate outside females' receptive period, potentially increasing the level of sperm competition and exacerbating sexual conflict over mating. The guppy ( Poecilia reticulata), an internally fertilizing fish, is a model system of such competition and conflict. Female guppies accept courtship and mate consensually only during receptive periods of the ovarian cycle but receive approximately one (mostly forced) mating attempt per minute both during and outside their sexually receptive phase. In addition, females can store viable sperm for months. We expected that guppy females would disfavour sperm received during their unreceptive period, possibly by modulating the quality and/or quantity of the components present in the ovarian fluid (OF) over the breeding cycle. Ovarian fluid has been shown to affect sperm velocity, a determinant of sperm competition success in this and other fishes. We found that in vitro sperm velocity is slower in OF collected from unreceptive females than in OF from receptive females. Visual stimulation with a potential partner prior to collection did not significantly affect in vitro sperm velocity. These results suggest that sperm received by unreceptive females may be disfavoured as sperm velocity likely affects the migration process and the number of sperm that reach storage sites.

Developmental Exposure to Low Levels of Ethinylestradiol Affects Play Behavior in Juvenile Female Rats.

PubMed

Zaccaroni, Marco; Massolo, Alessandro; Della Seta, Daniele; Farabollini, Francesca; Giannelli, Giulietta; Fusani, Leonida; Dessì-Fulgheri, Francesco

2018-05-01

Juvenile social play contributes to the development of adult social and emotional skills in humans and non-human animals, and is therefore a useful endpoint to study the effects of endocrine disrupters on behavior in animal models. Ethinylestradiol (EE 2 ) is a widely produced, powerful synthetic estrogen that is widespread in the environment mainly because is a component of the contraceptive pill. In addition, fetuses may be exposed to EE2 when pregnancy is undetected during contraceptive treatment. To understand whether exposure to EE 2 during gestation or lactation affects social play, we exposed 72 female Sprague-Dawley rats to EE 2 or vehicle either during gestation (gestation day (GD) 5 through GD 20) or during lactation (from postnatal day (PND) 1 through PND 21). Two doses of EE 2 were used to treat the dams: a lower dose in the range of possible environmental exposure (4 ng/kg/day) and a higher dose equivalent to that received during contraceptive treatment (400 ng/kg/day). Behavioral testing was carried out between PND 40 and 45. A principal component analysis of frequencies of behavioral items observed during play sessions identified three main components: defensive-like play, aggressive-like play, and exploration. Aggressive-like play was significantly increased by both doses of EE 2 , and the gestational administration was in general more effective than the lactational one. Defensive-like play and exploration were not significantly affected by treatment. This research showed that low and very low doses of EE 2 that mimic clinical or environmental exposure during development can affect important aspects of social behavior even during restricted time windows.

Ovarian development in a primitively eusocial wasp: social interactions affect behaviorally dominant and subordinate wasps in opposite directions relative to solitary females.

PubMed

Shukla, Shantanu; Pareek, Vidhi; Gadagkar, Raghavendra

2014-07-01

In many primitively eusocial wasp species new nests are founded either by a single female or by a small group of females. In the single foundress nests, the lone female develops her ovaries, lays eggs as well as tends her brood. In multiple foundress nests social interactions, especially dominance-subordinate interactions, result in only one 'dominant' female developing her ovaries and laying eggs. Ovaries of the remaining 'subordinate' cofoundresses remain suppressed and these individuals function as workers and tend the dominant's brood. Using the tropical, primitively eusocial polistine wasp Ropalidia marginata and by comparing wasps held in isolation and those kept as pairs in the laboratory, we demonstrate that social interactions affect ovarian development of dominant and subordinate wasps among the pairs in opposite directions, suppressing the ovaries of the subordinate member of the pair below that of solitary wasps and boosting the ovaries of dominant member of the pair above that of solitary females. In addition to being of physiological interest, such mirror image effects of aggression on the ovaries of the aggressors and their victims, suggest yet another mechanism by which subordinates can enhance their indirect fitness and facilitate the evolution of worker behavior by kin selection. Copyright © 2014 Elsevier B.V. All rights reserved.

Developmental programming by androgen affects the circadian timing system in female mice.

PubMed

Mereness, Amanda L; Murphy, Zachary C; Sellix, Michael T

2015-04-01

Circadian clocks play essential roles in the timing of events in the mammalian hypothalamo-pituitary-ovarian (HPO) axis. The molecular oscillator driving these rhythms has been localized to tissues of the HPO axis. It has been suggested that synchrony among these oscillators is a feature of normal reproductive function. The impact of fertility disorders on clock function and the role of the clock in the etiology of endocrine pathology remain unknown. Polycystic ovarian syndrome (PCOS) is a particularly devastating fertility disorder, affecting 5%-10% of women at childbearing age with features including a polycystic ovary, anovulation, and elevated serum androgen. Approximately 40% of these women have metabolic syndrome, marked by hyperinsulinemia, dyslipidemia, and insulin resistance. It has been suggested that developmental exposure to excess androgen contributes to the etiology of fertility disorders, including PCOS. To better define the role of the timing system in these disorders, we determined the effects of androgen-dependent developmental programming on clock gene expression in tissues of the metabolic and HPO axes. Female PERIOD2::luciferase (PER2::LUC) mice were exposed to androgen (dihydrotestosterone [DHT]) in utero (Days 16-18 of gestation) or for 9-10 wk (DHT pellet) beginning at weaning (pubertal androgen excess [PAE]). As expected, both groups of androgen-treated mice had disrupted estrous cycles. Analysis of PER2::LUC expression in tissue explants revealed that excess androgen produced circadian misalignment via tissue-dependent effects on phase distribution. In vitro treatment with DHT differentially affected the period of PER2::LUC expression in tissue explants and granulosa cells, indicating that androgen has direct and tissue-specific effects on clock gene expression that may account for the effects of developmental programming on the timing system. © 2015 by the Society for the Study of Reproduction, Inc.

Aging affects the response of female rats to a hypercaloric diet.

PubMed

Arbo, B D; Niches, G; Zanini, P; Bassuino, D M; Driemeier, D; Ribeiro, M F; Cecconello, A L

2018-01-01

Metabolic syndrome is a major risk factor for the development of cardiovascular diseases and diabetes, among other conditions. Studies have shown that aging and metabolic syndrome share several metabolic alterations, and that aged individuals, in particular females, are at an increased risk of developing metabolic disorders. Although several studies have investigated the effects of hypercaloric diets in the development of obesity and metabolic syndrome in young animals, few studies have investigated these parameters in aged animals, especially in females. Therefore, the aim of this study was to investigate the effects of a hypercaloric diet in metabolic parameters of young and aged female rats, including its effects on lipid and glycemic profile and on liver lipid content. When compared to young animals, the aged rats presented increased serum levels of triglycerides and decreased serum levels of HDL cholesterol and glycemia, as well as increased hepatic levels of triglycerides and total cholesterol. The hypercaloric diet increased food intake, body weight gain and adiposity index, leading both young and aged animals to a dyslipidemia, represented by increased serum levels of triglycerides. The hypercaloric diet increased the glycemia and the HOMA index only in the young animals. On the other hand, the diet increased the frequency of hepatocellular microvacuolar degeneration only in the aged animals. In summary, it was observed that the females from different ages respond differently to hypercaloric diet intake: while the aged animals were more resistant to the changes in the glycemic profile, they were more susceptible to the hepatic damage caused by this diet. Copyright © 2017 Elsevier Inc. All rights reserved.

Radio-transmitters do not affect seasonal productivity of female Golden-winged Warblers

USGS Publications Warehouse

Streby, Henry M.; Peterson, Sean M.; Gesmundo, Callie; Johnson, Michael K.; Fish, Alexander C.; Lehman, Justin A.; Andersen, David E.

2013-01-01

Investigating the potential effects of handling and marking techniques on study animals is important for correct interpretation of research results and to effect progress in data-collection methods. Few investigators have compared the reproductive output of radio-tagged and non-radio-tagged songbirds, and no one to date has examined the possible effect of radio-tagging adult songbirds on the survival of their fledglings. In 2011 and 2012, we compared several parameters of reproductive output of two groups of female Golden-winged Warblers (Vermivora chrysoptera) breeding in Minnesota, including 45 females with radio-transmitters and 73 females we did not capture, handle, or mark. We found no difference between groups in clutch sizes, hatching success, brood sizes, length of incubation and nestling stages, fledging success, number of fledglings, or survival of fledglings to independence. Thus, radio-tags had no measurable impact on the productivity of female Golden-winged Warblers. Our results build upon previous studies where investigators have reported no effects of radio-tagging on the breeding parameters of songbirds by also demonstrating no effect of radio-tagging through the post-fledging period and, therefore, the entire breeding season.

MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome

PubMed Central

Tai, Derek J. C.; Liu, Yen C.; Hsu, Wei L.; Ma, Yun L.; Cheng, Sin J.; Liu, Shau Y.; Lee, Eminy H. Y.

2016-01-01

The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP2 SUMOylation is induced by NMDA, IGF-1 and CRF in the rat brain. MeCP2 SUMOylation releases CREB from the repressor complex and enhances Bdnf mRNA expression. Several MECP2 mutations identified in RTT patients show decreased MeCP2 SUMOylation. Re-expression of wild-type MeCP2 or SUMO-modified MeCP2 in Mecp2-null neurons rescues the deficits of social interaction, fear memory and LTP observed in Mecp2 conditional knockout (cKO) mice. These results together reveal an important role of MeCP2 SUMOylation in social interaction, memory and synaptic plasticity, and that abnormal MeCP2 SUMOylation is implicated in RTT. PMID:26842955

Altered erythrocyte membrane fatty acid profile in typical Rett syndrome: effects of omega-3 polyunsaturated fatty acid supplementation.

PubMed

Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia; Durand, Thierry; Galano, Jean-Marie; Cortelazzo, Alessio; Zollo, Gloria; Guerranti, Roberto; Gonnelli, Stefano; Caffarelli, Carla; Rossi, Marcello; Pecorelli, Alessandra; Valacchi, Giuseppe; Ciccoli, Lucia; Hayek, Joussef

2014-11-01

This study mainly aims at examining the erythrocyte membrane fatty acid (FAs) profile in Rett syndrome (RTT), a genetically determined neurodevelopmental disease. Early reports suggest a beneficial effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on disease severity in RTT. A total of 24 RTT patients were assigned to ω-3 PUFAs-containing fish oil for 12 months in a randomized controlled study (average DHA and EPA doses of 72.9, and 117.1mg/kgb.w./day, respectively). A distinctly altered FAs profile was detectable in RTT, with deficient ω-6 PUFAs, increased saturated FAs and reduced trans 20:4 FAs. FAs changes were found to be related to redox imbalance, subclinical inflammation, and decreased bone density. Supplementation with ω-3 PUFAs led to improved ω-6/ω-3 ratio and serum plasma lipid profile, decreased PUFAs peroxidation end-products, normalization of biochemical markers of inflammation, and reduction of bone hypodensity as compared to the untreated RTT group. Our data indicate that a significant FAs abnormality is detectable in the RTT erythrocyte membranes and is partially rescued by ω-3 PUFAs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females.

PubMed

Depienne, Christel; Bouteiller, Delphine; Keren, Boris; Cheuret, Emmanuel; Poirier, Karine; Trouillard, Oriane; Benyahia, Baya; Quelin, Chloé; Carpentier, Wassila; Julia, Sophie; Afenjar, Alexandra; Gautier, Agnès; Rivier, François; Meyer, Sophie; Berquin, Patrick; Hélias, Marie; Py, Isabelle; Rivera, Serge; Bahi-Buisson, Nadia; Gourfinkel-An, Isabelle; Cazeneuve, Cécile; Ruberg, Merle; Brice, Alexis; Nabbout, Rima; Leguern, Eric

2009-02-01

Dravet syndrome (DS) is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations) were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences) in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism.

Factors Affecting Female Attitude Formation toward Science. Specific Reference to 12-14 Year Old Female Adolescents and Their Affective Orientation toward Middle School Science.

ERIC Educational Resources Information Center

Schreiber, Deborah A.

This paper: (1) briefly reviews the existing literature which supports that female adolescents possess significantly more negative attitudes toward middle school science than do males; (2) examines the process of gender socialization in the United States to establish the socio-cultural and social psychological framework within which an attitudinal…

Evolutionary Influences on Attribution and Affect

PubMed Central

Brown, Jennie; Trafimow, David

2017-01-01

Evolutionary theory was applied to Reeder and Brewer's schematic theory and Trafimow's affect theory to extend this area of research with five new predictions involving affect and ability attributions, comparing morality and ability attributions, gender differences, and reaction times for affect and attribution ratings. The design included a 2 (Trait Dimension Type: HR, PR) × 2 (Behavior Type: morality, ability) × 2 (Valence: positive, negative) × 2 (Replication: original, replication) × 2 (Sex: female or male actor) × 2 (Gender: female or male participant) × 2 (Order: attribution portion first, affect portion first) mixed design. All factors were within participants except the order and participant gender. Participants were presented with 32 different scenarios in which an actor engaged in a concrete behavior after which they made attributions and rated their affect in response to the behavior. Reaction times were measured during attribution and affect ratings. In general, the findings from the experiment supported the new predictions. Affect was related to attributions for both morality and ability related behaviors. Morality related behaviors received more extreme attribution and affect ratings than ability related behaviors. Female actors received stronger attribution and affect ratings for diagnostic morality behaviors compared to male actors. Male and female actors received similar attribution and affect ratings for diagnostic ability behaviors. Diagnostic behaviors were associated with lower reaction times than non-diagnostic behaviors. These findings demonstrate the utility of evolutionary theory in creating new hypotheses and empirical findings in the domain of attribution. PMID:29312092

Evolutionary Influences on Attribution and Affect.

PubMed

Brown, Jennie; Trafimow, David

2017-01-01

Evolutionary theory was applied to Reeder and Brewer's schematic theory and Trafimow's affect theory to extend this area of research with five new predictions involving affect and ability attributions, comparing morality and ability attributions, gender differences, and reaction times for affect and attribution ratings. The design included a 2 (Trait Dimension Type: HR, PR) × 2 (Behavior Type: morality, ability) × 2 (Valence: positive, negative) × 2 (Replication: original, replication) × 2 (Sex: female or male actor) × 2 (Gender: female or male participant) × 2 (Order: attribution portion first, affect portion first) mixed design. All factors were within participants except the order and participant gender. Participants were presented with 32 different scenarios in which an actor engaged in a concrete behavior after which they made attributions and rated their affect in response to the behavior. Reaction times were measured during attribution and affect ratings. In general, the findings from the experiment supported the new predictions. Affect was related to attributions for both morality and ability related behaviors. Morality related behaviors received more extreme attribution and affect ratings than ability related behaviors. Female actors received stronger attribution and affect ratings for diagnostic morality behaviors compared to male actors. Male and female actors received similar attribution and affect ratings for diagnostic ability behaviors. Diagnostic behaviors were associated with lower reaction times than non-diagnostic behaviors. These findings demonstrate the utility of evolutionary theory in creating new hypotheses and empirical findings in the domain of attribution.

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.

Third harmonic generation imaging of intact human cerebral organoids to assess key components of early neurogenesis in Rett Syndrome (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yildirim, Murat; Feldman, Danielle; Wang, Tianyu; Ouzounov, Dimitre G.; Chou, Stephanie; Swaney, Justin; Chung, Kwanghun; Xu, Chris; So, Peter T. C.; Sur, Mriganka

2017-02-01

Rett Syndrome (RTT) is a pervasive, X-linked neurodevelopmental disorder that predominantly affects girls. It is mostly caused by a sporadic mutation in the gene encoding methyl CpG-binding protein 2 (MeCP2).The clinical features of RTT are most commonly reported to emerge between the ages of 6-18 months and implicating RTT as a disorder of postnatal development. However, a variety of recent evidence from our lab and others demonstrates that RTT phenotypes are present at the earliest stages of brain development including neurogenesis, migration, and patterning in addition to stages of synaptic and circuit development and plasticity. We have used RTT patient-derived induced pluripotent stem cells to generate 3D human cerebral organoids that can serve as a model for human neurogenesis in vitro. We aim to expand on our existing findings in order to determine aberrancies at individual stages of neurogenesis by performing structural and immunocytochemical staining in isogenic control and MeCP2-deficient organoids. In addition, we aim to use Third Harmonic Generation (THG) microscopy as a label-free, nondestructive 3D tissue visualization method in order to gain a complete understanding of the structural complexity that underlies human neurogenesis. As a proof of concept, we have performed THG imaging in healthy intact human cerebral organoids cleared with SWITCH. We acquired an intrinsic THG signal with the following laser configurations: 400 kHz repetition rate, 65 fs pulse width laser at 1350 nm wavelength. In these THG images, nuclei are clearly delineated and cross sections demonstrate the depth penetration capacity (< 1mm) that extends throughout the organoid. Imaging control and MeCP2-deficient human cerebral organoids in 2D sections reveals structural and protein expression-based alterations that we expect will be clearly elucidated via both THG and three-photon fluorescence microscopy.

Female Sex But Not Original Indication Affects Physical Activity After Liver Transplant: A Prospective, Single Center Study.

PubMed

Kotarska, Katarzyna; Wunsch, Ewa; Raszeja-Wyszomirska, Joanna; Kempińska-Podhorodecka, Agnieszka; Wójcicki, Maciej; Milkiewicz, Piotr

2015-06-01

Physical activity has an effect on long-term recovery after major surgical operations including liver transplant. Seven-Day Physical Activity Recall Questionnaire is a semistructured survey that assesses an individual's time spent in physical activity, strength, and flexibility activities during the 7 days prior to the interview. In this study we applied the Seven-Day Physical Activity Recall Questionnaire in patients who underwent liver transplant in our center. We surveyed 107 consecutive patients (62 male and 45 female), who were ≥ 6 months after liver transplant. Patients were divided into 3 groups, depending on time after liver transplant: group A (n = 21), 6 to 12 months posttransplant; group B (n = 48), 13 to 36 months posttransplant; and group C (n = 38), > 37 months posttransplant. Relations were analyzed between physical activity and various factors including sex, age at procedure and survey, time after grafting, original diagnosis, and body mass index. Female patients were significantly less active in daily and weekly measurements (981 ± 212 kcal vs 1267 ± 229 kcal; P < .0001) (6864 ± 1484 kcal vs 8866 ± 1607 kcal; P < .0001). There was a negative correlation between physical activity and age at transplant (P = .02) and survey (P = .02). Neither the time after liver transplant nor the original diagnosis before grafting affected physical activity. Female patients, when assessed with Seven-Day Physical Activity Recall Questionnaire, were significantly less physically active than male subjects after liver transplant. Younger patients were more active, but primary diagnosis had no significant effect on physical activity after grafting.

Sexual competition affects biomass partitioning, carbon-nutrient balance, Cd allocation and ultrastructure of Populus cathayana females and males exposed to Cd stress.

PubMed

Chen, Juan; Duan, Baoli; Xu, Gang; Korpelainen, Helena; Niinemets, Ülo; Li, Chunyang

2016-11-01

Although increasing attention has been paid to plant adaptation to soil heavy metal contamination, competition and neighbor effects have been largely overlooked, especially in dioecious plants. In this study, we investigated growth as well as biochemical and ultrastructural responses of Populus cathayana Rehder females and males to cadmium (Cd) stress under different sexual competition patterns. The results showed that competition significantly affects biomass partitioning, photosynthetic capacity, leaf and root ultrastructure, Cd accumulation, the contents of polyphenols, and structural and nonstructural carbohydrates. Compared with single-sex cultivation, plants of opposite sexes exposed to sexual competition accumulated more Cd in tissues and their growth was more strongly inhibited, indicating enhanced Cd toxicity under sexual competition. Under intrasexual competition, females showed greater Cd accumulation, more serious damage at the ultrastructural level and greater reduction in physiological activity than under intersexual competition, while males performed better under intrasexual competition than under intersexual competition. Males improved the female microenvironment by greater Cd uptake and lower resource consumption under intersexual competition. These results demonstrate that the sex of neighbor plants and competition affect sexual differences in growth and in key physiological processes under Cd stress. The asymmetry of sexual competition highlighted here might regulate population structure, and spatial segregation and phytoremediation potential of both sexes in P. cathayana growing in heavy metal-contaminated soils. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reinforcement Sensitivity Underlying Treatment-Seeking Smokers’ Affect, Smoking Reinforcement Motives, and Affective Responses

PubMed Central

Cui, Yong; Robinson, Jason D.; Engelmann, Jeffrey M.; Lam, Cho Y.; Minnix, Jennifer A.; Karam-Hage, Maher; Wetter, David W.; Dani, John A.; Kosten, Thomas R.; Cinciripini, Paul M.

2014-01-01

Nicotine dependence has been suggested to be related to reinforcement sensitivity, which encompasses behavioral predispositions either to avoid aversive (behavioral inhibition) or to approach appetitive (behavioral activation) stimuli. Reinforcement sensitivity may shape motives for nicotine use and offer potential targets for personalized smoking cessation therapy. However, little is known regarding how reinforcement sensitivity is related to motivational processes implicated in the maintenance of smoking. Additionally, women and men differ in reinforcement sensitivity, and such difference may cause distinct relationships between reinforcement sensitivity and motivational processes for female and male smokers. In this study, we characterized reinforcement sensitivity in relation to affect, smoking-related reinforcement motives, and affective responses, using self-report and psychophysiological measures, in over 200 smokers before treating them. The Behavioral Inhibition/Activation Scales (BIS/BAS; Carver & White, 1994) was used to measure reinforcement sensitivity. In female and male smokers, BIS was similarly associated with negative affect and negative reinforcement of smoking. But positive affect was positively associated with BAS Drive scores in male smokers, and this association was reversed in female smokers. BIS was positively associated with corrugator electromyographic reactivity towards negative stimuli and left frontal electroencephalogram alpha asymmetry. Female and male smokers showed similar relationships for these physiological measures. These findings suggest that reinforcement sensitivity underpins important motivational processes (e.g., affect), and gender is a moderating factor for these relationships. Future personalized smoking intervention, particularly among more dependent treatment-seeking smokers, may experiment to target individual differences in reinforcement sensitivity. PMID:25621416

[Anesthetic management of a patient with Rett syndrome associated with trismus and apnea attacks].

PubMed

Kawasaki, Eri; Mishima, Yasunori; Ito, Takahiko; Ito, Asuka; Takaseya, Hikari; Kameyama, Naomitsu; Fukugasako, Hisato; Ushijima, Kazuo

2012-01-01

Rett syndrome (RTT) is a congenital neurological disorder associated with mutations in the gene encoding MECP2 on the X chromosome. An 18-year-old woman (150 cm in height and 29 kg in weight) had been diagnosed with RTT and showed myotonic trismus, frequent attacks of apnea, mental retardation, spastic paraplegia, scoliosis, and microcephalus with micrognathia. She was scheduled to undergo laparoscopic fundoplication and gastrostomy under general anesthesia. Nasal bronchofiberscopic intubation (BFI) was planned because difficult airway due to trismus and micrognathia was expected. Referring to the bispectral index (BIS), anesthesia was induced with intermittent intravenous thiopental (total 125 mg), resulting in successful opening of the mouth by 1.5 of a finger width and establishment of manual ventilation. Following intravenous administration of rocuronium (20 mg), oral BFI was easily accomplished despite Cormack grade III. Anesthesia was satisfactorily maintained with inhalation of sevoflurane (1.0-1.5%) and continuous infusion of remifentanil (0.1-0.2 microg x kg(-1) x min(-1)) with the BIS value ranging from 30 to 50. She recovered smoothly from anesthesia using sugammadex (50 mg). However, she immediately demonstrated trismus and an attack of apnea with shivering, which were successfully resolved by warming the body and intravenous fentanyl (50 microg bolus and subsequent infusion at a rate of 10 microg x hr(-1)). The postoperative course was uneventful. Characteristically, RTT shows an extremely wide range of neurological symptoms. Therefore, it is of great importance to respond to each of those symptoms during the perioperative management of patients with RTT.

Factors that affect the physical science career interest of female students: Testing five common hypotheses

NASA Astrophysics Data System (ADS)

Hazari, Zahra; Potvin, Geoff; Lock, Robynne M.; Lung, Florin; Sonnert, Gerhard; Sadler, Philip M.

2013-12-01

There are many hypotheses regarding factors that may encourage female students to pursue careers in the physical sciences. Using multivariate matching methods on national data drawn from the Persistence Research in Science and Engineering (PRiSE) project (n=7505), we test the following five commonly held beliefs regarding what factors might impact females’ physical science career interest: (i) having a single-sex physics class, (ii) having a female physics teacher, (iii) having female scientist guest speakers in physics class, (iv) discussing the work of female scientists in physics class, and (v) discussing the underrepresentation of women in physics class. The effect of these experiences on physical science career interest is compared for female students who are matched on several factors, including prior science interests, prior mathematics interests, grades in science, grades in mathematics, and years of enrollment in high school physics. No significant effects are found for single-sex classes, female teachers, female scientist guest speakers, and discussing the work of female scientists. However, discussions about women’s underrepresentation have a significant positive effect.

Factors affecting winter survival of female mallards in the lower Mississippi alluvial valley

USGS Publications Warehouse

Davis, B.E.; Afton, A.D.; Cox, R.R.

2011-01-01

The lower Mississippi Alluvial Valley (hereafter LMAV) provides winter habitat for approximately 40% of the Mississippi Flyway's Mallard (Anas platyrhynhcos) population; information on winter survival rates of female Mallards in the LMAV is restricted to data collected prior to implementation of the North American Waterfowl Management Plan. To estimate recent survival and cause-specific mortality rates in the LMAV, 174 radio-marked female Mallards were tracked for a total of 11,912 exposure days. Survival varied by time periods defined by hunting seasons, and females with lower body condition (size adjusted body mass) at time of capture had reduced probability of survival. Female survival was less and the duration of our tracking period was greater than those in previous studies of similarly marked females in the LMAV; the product-limit survival estimate (??????SE) through the entire tracking period (136 days) was 0.54 ??0.10. Cause-specific mortality rates were 0.18 ??0.04 and 0.34 ??0.12 for hunting and other sources of mortality, respectively; the estimated mortality rate from other sources (including those from avian, mammalian, or unknown sources) was higher than mortality from non-hunting sources reported in previous studies of Mallards in the LMAV. Models that incorporate winter survival estimates as a factor in Mallard population growth rates should be adjusted for these reduced winter survival estimates.

Characterizing Male–Female Interactions Using Natural Genetic Variation in Drosophila melanogaster

PubMed Central

Reinhart, Michael; Carney, Tara; Clark, Andrew G.

2015-01-01

Drosophila melanogaster females commonly mate with multiple males establishing the opportunity for pre- and postcopulatory sexual selection. Traits impacting sexual selection can be affected by a complex interplay of the genotypes of the competing males, the genotype of the female, and compatibilities between the males and females. We scored males from 96 2nd and 94 3rd chromosome substitution lines for traits affecting reproductive success when mated with females from 3 different genetic backgrounds. The traits included male-induced female refractoriness, male remating ability, the proportion of offspring sired under competitive conditions and male-induced female fecundity. We observed significant effects of male line, female genetic background, and strong male by female interactions. Some males appeared to be “generalists” and performed consistently across the different females; other males appeared to be “specialists” and performed very well with a particular female and poorly with others. “Specialist” males did not, however, prefer to court those females with whom they had the highest reproductive fitness. Using 143 polymorphisms in male reproductive genes, we mapped several genes that had consistent effects across the different females including a derived, high fitness allele in Acp26Aa that may be the target of adaptive evolution. We also identified a polymorphism upstream of PebII that may interact with the female genetic background to affect male-induced refractoriness to remating. These results suggest that natural variation in PebII might contribute to the observed male–female interactions. PMID:25425680

Reinforcement sensitivity underlying treatment-seeking smokers' affect, smoking reinforcement motives, and affective responses.

PubMed

Cui, Yong; Robinson, Jason D; Engelmann, Jeffrey M; Lam, Cho Y; Minnix, Jennifer A; Karam-Hage, Maher; Wetter, David W; Dani, John A; Kosten, Thomas R; Cinciripini, Paul M

2015-06-01

Nicotine dependence has been suggested to be related to reinforcement sensitivity, which encompasses behavioral predispositions either to avoid aversive (behavioral inhibition) or to approach appetitive (behavioral activation) stimuli. Reinforcement sensitivity may shape motives for nicotine use and offer potential targets for personalized smoking cessation therapy. However, little is known regarding how reinforcement sensitivity is related to motivational processes implicated in the maintenance of smoking. Additionally, women and men differ in reinforcement sensitivity, and such difference may cause distinct relationships between reinforcement sensitivity and motivational processes for female and male smokers. In this study, the authors characterized reinforcement sensitivity in relation to affect, smoking-related reinforcement motives, and affective responses, using self-report and psychophysiological measures, in over 200 smokers before treating them. The Behavioral Inhibition/Activation Scales (BIS/BAS; Carver & White, 1994) was used to measure reinforcement sensitivity. In female and male smokers, BIS was similarly associated with negative affect and negative reinforcement of smoking. However, positive affect was positively associated with BAS Drive scores in male smokers, and this association was reversed in female smokers. BIS was positively associated with corrugator electromyographic reactivity toward negative stimuli and left frontal electroencephalogram alpha asymmetry. Female and male smokers showed similar relationships for these physiological measures. These findings suggest that reinforcement sensitivity underpins important motivational processes (e.g., affect), and gender is a moderating factor for these relationships. Future personalized smoking intervention, particularly among more dependent treatment-seeking smokers, may experiment to target individual differences in reinforcement sensitivity. (PsycINFO Database Record (c) 2015 APA, all rights

Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine–serotonin systems in the prefrontal cortex of juvenile female rats

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

Castro, Beatriz; Sánchez, Pilar; Torres, Jesús M., E-mail: torrespi@ugr.es

Background: Early-life exposure to the endocrine disruptor bisphenol A (BPA) affects brain function and behavior, which might be attributed to its interference with hormonal steroid signaling and/or neurotransmitter systems. Alternatively, the use of structural analogs of BPA, mainly bisphenol F (BPF) and bisphenol S (BPS), has increased recently. However, limited in vivo toxicity data exist. Objectives: We investigated the effects of BPA, BPF and BPS on 5α-reductase (5α-R), a key enzyme involved in neurosteroidogenesis, as well as on dopamine (DA)- and serotonin (5-HT)-related genes, in the prefrontal cortex (PFC) of juvenile female rats. Methods: Gestating Wistar rats were treated withmore » either vehicle or 10 μg/kg/day of BPA, BPF or BPS from gestational day 12 to parturition. Then, female pups were exposed from postnatal day 1 through day 21 (PND21), when they were euthanized and RT-PCR, western blot and quantitative PCR-array experiments were performed. Results: BPA decreased 5α-R2 and 5α-R3 mRNA and protein levels, while both BPF and BPS decreased 5α-R3 mRNA levels in PFC at PND21. Further, BPA, BPF and BPS significantly altered, respectively, the transcription of 25, 56 and 24 genes out of the 84 DA and 5-HT-related genes assayed. Of particular interest was the strong induction by all these bisphenols of Cyp2d4, implicated in corticosteroids synthesis. Conclusions: Our results demonstrate for the first time that BPA, BPF and BPS differentially affect 5α-R and genes related to DA/5-HT systems in the female PFC. In vivo evidence of the potential adverse effects of BPF and BPS in the brain of mammals is provided in this work, raising questions about the safety of these chemicals as substitutes for BPA. - Highlights: • Juvenile prefrontal cortex of female rats exposed to bisphenol A, F or S was analyzed. • We provide the first in vivo data of BPF and BPS effects in mammal brain. • BPA, BPF and BPS differently affected dopamine and serotonin

Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report.

PubMed

Santosh, P J; Bell, L; Lievesley, K; Singh, J; Fiori, F

2016-11-29

Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT. The prototypical beta blocker propranolol has been used to manage sympathetic hyperactivity in patients with RTT. A 13 year old girl with RTT was referred to the Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust. Her clinical picture included disordered breathing with concomitant hyperventilation and apnoea, epilepsy, scoliosis, no QT prolongation (QT/QTc [372/467 ms on automated electrocardiogram [ECG], but manually calculated to be 440 ms]), no cardiac abnormalities (PR interval: 104 ms, QRS duration: 78 ms), and generalised anxiety disorder (ICD-10-CM Diagnosis Code F41.1). She was also constipated and was fed via percutaneous endoscopic gastrostomy (PEG). To manage the dysautonomia, propranolol was given (5 mg and 10 mg) and in parallel her physiological parameters, including heart rate, skin temperature and skin transpiration, were monitored continuously for 24 h as she went about her activities of daily living. Whilst her skin temperature increased and skin transpiration decreased, unexpectedly there was a significant paradoxical increase in the patient's average heart rate following propranolol treatment. Here, we present a unique case of a paradoxical increase in heart rate response following propranolol treatment for managing dysautonomia in a child with RTT. Further studies are warranted to better understand the underlying dysautonomia in patients with RTT and

What Health Issues or Conditions Are Specific to Women Only?

MedlinePlus

... Research Information Find a Study Resources and Publications Turner Syndrome Condition Information NICHD Research Information Find a Study ... disorders and conditions that affect only women include Turner syndrome , Rett syndrome , and ovarian and cervical cancers. Issues ...

Sensory factors affecting female consumers' acceptability of nail polish.

PubMed

Sun, C; Koppel, K; Adhikari, K

2015-12-01

The objectives of this study were to determine what sensory factors impact consumers' acceptability of nail polishes, to explore how these sensory factors impact consumers' acceptability of nail polishes, to investigate whether there are any consumer segments according to their overall acceptability on different nail polishes and to scrutinize how the consumer segments are related to the sensory factors. Ninety-eight females participated in a nail polish consumer study at Kansas State University. Eight commercial products belonging to four categories - regular (REG), gel (GEL), flake (FLK) and water-based (WAT) - were evaluated. Each nail polish sample was evaluated twice by each participant in two different tasks - a task devoted to applying and evaluating the product and a task devoted to observing the appearance and evaluating the product. Pearson's correlation analysis, analysis of variance (ANOVA), external preference mapping, cluster analysis and internal preference mapping were applied for data analysis. Participants' scores of overall liking of the nail polishes were similar in the application task and in the observation task. In general, participants liked the REG and GEL product samples more than the FLK and WAT samples. Among all the sensory attributes, appearance attributes were the major factors that affected participants' overall liking. Aroma seemed to be a minor factor to participants' overall liking. Some sensory attributes, such as runny, shininess, opacity, spreadability, smoothness, coverage and wet appearance, were found to drive participants' overall acceptability positively, whereas others such as pinhole, fatty-edges, blister, brushlines, pearl-like, flake-protrusion, glittery and initial-drag impacted participants' overall acceptability negatively. Four clusters of participants were identified according to their overall liking scores from both the application task and the observation task. Participants' acceptability, based on different

Methamphetamine enhances sexual behavior in female rats.

PubMed

Winland, Carissa; Haycox, Charles; Bolton, Jessica L; Jampana, Sumith; Oakley, Benjamin J; Ford, Brittany; Ornelas, Laura; Burbey, Alexandra; Marquette, Amber; Frohardt, Russell J; Guarraci, Fay A

2011-06-01

The present study evaluated the effects of methamphetamine (MA) on sexual behavior in female rats. In Experiment 1, ovariectomized, hormone-primed rats were injected with MA (1.0mg/kg, i.p.) or saline prior to a test for mate choice wherein females could mate with two males simultaneously. Female rats treated with saline returned to their preferred mate faster after receiving intromissions and visited their preferred mate at a higher rate than their non-preferred mate. In contrast, MA-treated female rats spent a similar amount of time with their preferred and non-preferred mate and failed to return to their preferred mate faster than to their non-preferred mate following intromissions. Two weeks later, the females received the same drug treatment but were tested for partner preference wherein females could spend time near a male or female stimulus rat. All subjects spent more time near the male stimulus than the female stimulus. However, the MA-treated rats visited the male stimulus more frequently and spent less time near the female stimulus than the saline-treated rats. Similar to Experiment 1, female rats in Experiment 2 were tested for mate choice and then two weeks later tested for partner preference; however, females received three daily injections of MA (1.0mg/kg, i.p.) or saline. Females treated chronically with MA returned to both males faster following intromissions than females treated with saline, independent of preference (i.e., preferred mate and non-preferred mate). Furthermore, MA-treated rats were more likely to leave either male (i.e., preferred or non-preferred mate) than saline-treated rats after receiving sexual stimulation. Although MA-treated subjects spent more time near the male stimulus than the female stimulus, they spent less time near either when compared to saline-treated subjects. The present results demonstrate that MA affects sexual behavior in female rats partly by increasing locomotion and partly by directly affecting sexual

Acute withdrawal but not long-term withdrawal from methamphetamine affects sexual behavior in female rats.

PubMed

Thibodeau, Rachel B; Ornelas, Laura C; Romero, Jordan; Memos, Nicoletta; Scheible, Matthew; Avila, Alfred; Schumacher, Abby; Navarro, April; Zimmermann, Karen; Cuenod, Bethany A; Frohardt, Russell J; Guarraci, Fay A

2013-02-01

The present study was designed to investigate the long-term effects of repeated methamphetamine (MA) exposure on sexual motivation in female rats tested after a period of drug abstinence. In Experiment 1, female subjects received three injections of MA (1.0mg/kg/day, every other day) or saline and were tested for paced mating behavior (where females could control the receipt of sexual stimulation from one male rat) 21 days after their last injection. In Experiment 2, female subjects received 12 consecutive injections of MA (1.0mg/kg/day) or saline and were tested for mate choice (where females could control the receipt of sexual stimulation from two male rats simultaneously) 6 days after their last injection. Experiment 3 was identical to Experiment 2 except that female subjects received no baseline mating test and were tested for mate choice 24h and 6 days after their last injection. Open field tests were conducted in each experiment to measure locomotor activity after repeated exposure to MA. Although repeated MA exposure increased locomotor activity, mating behavior was not facilitated after either a short (6 days) or long (21 days) period of drug abstinence. Nevertheless, sexual behavior was disrupted during the 24h acute withdrawal period. Therefore, although the present study found no evidence of cross-sensitization between female sexual behavior and MA after either a short or a long period of drug abstinence, sexual behavior in sexually naïve female rats is sensitive to the depressive state associated with acute withdrawal from MA. In conclusion, the results of the present study suggest that MA acts differently from other psychomotor stimulants, and that the effects of MA withdrawal on sexual behavior differ between male and female rats. Copyright © 2012 Elsevier Inc. All rights reserved.

CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling.

PubMed

Chen, Qian; Zhu, Yong-Chuan; Yu, Jing; Miao, Sheng; Zheng, Jing; Xu, Li; Zhou, Yang; Li, Dan; Zhang, Chi; Tao, Jiong; Xiong, Zhi-Qi

2010-09-22

Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.

Male accessory gland substances from Aedes albopictus affect the locomotor activity of Aedes aegypti females

PubMed Central

Lima-Camara, Tamara Nunes; Codeço, Claudia Torres; Honório, Nildimar Alves; Bruno, Rafaela Vieira; Peixoto, Alexandre Afranio; Lounibos, Leon Philip

2013-01-01

Dengue is one of the world’s most important mosquito-borne diseases and is usually transmitted by one of two vector species: Aedes aegypti or Aedes albopictus . These two diurnal mosquitoes are frequently found coexisting in similar habitats, enabling interactions between adults, such as cross-mating. The objective of this study was to assess cross-mating between Ae. aegypti females and Ae. albopictus males under artificial conditions and evaluate the locomotor activity of Ae. aegypti virgin females injected with male accessory gland (MAG) homogenates to infer the physiological and behavioural responses to interspecific mating. After seven days of exposure, 3.3-16% of Ae. aegypti females mated with Ae. albopictus males. Virgin Ae. aegypti females injected with conspecific and heterospecific MAGs showed a general decrease in locomotor activity compared to controls and were refractory to mating with conspecific males. The reduction in diurnal locomotor activity induced by injections of conspecific or heterospecific MAGs is consistent with regulation of female reproductive activities by male substances, which are capable of sterilising female Ae. aegypti through satyrisation by Ae. albopictus . PMID:24473799

Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females

PubMed Central

Treadway, Michael T.; Valeri, Linda; Douglas, Samuel

2017-01-01

The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response (n = 10), moderate-response (n = 21), and mild-response (n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability. SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how

Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.

PubMed

Admon, Roee; Treadway, Michael T; Valeri, Linda; Mehta, Malavika; Douglas, Samuel; Pizzagalli, Diego A

2017-08-16

The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response ( n = 10), moderate-response ( n = 21), and mild-response ( n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability. SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how

Comparing Parental Well-Being and Its Determinants Across Three Different Genetic Disorders Causing Intellectual Disability.

PubMed

Mori, Yuka; Downs, Jenny; Wong, Kingsley; Heyworth, Jane; Leonard, Helen

2018-05-01

Using the Short Form 12 Health Survey this cross-sectional study examined parental well-being in caregivers of children with one of three genetic disorders associated with intellectual disability; Down syndrome, Rett syndrome and the CDKL5 disorder. Data were sourced from the Western Australian Down Syndrome (n = 291), Australian Rett Syndrome (n = 187) and International CDKL5 Disorder (n = 168) Databases. Among 596 mothers (median age, years 43.7; 24.6-72.2), emotional well-being was poorer than general female populations across age groups. Multivariate linear regression identified the poorest well-being in parents of children with the CDKL5 disorder, a rare but severe and complex encephalopathy, and negative associations with increased clinical severity irrespective of diagnosis. These findings are important for those providing healthcare and social services for these populations.

Early Vocal Development in Autism Spectrum Disorder, Rett Syndrome, and Fragile X Syndrome: Insights from Studies using Retrospective Video Analysis.

PubMed

Roche, Laura; Zhang, Dajie; Bartl-Pokorny, Katrin D; Pokorny, Florian B; Schuller, Björn W; Esposito, Gianluca; Bölte, Sven; Roeyers, Herbert; Poustka, Luise; Gugatschka, Markus; Waddington, Hannah; Vollmann, Ralf; Einspieler, Christa; Marschik, Peter B

2018-03-01

This article provides an overview of studies assessing the early vocalisations of children with autism spectrum disorder (ASD), Rett syndrome (RTT), and fragile X syndrome (FXS) using retrospective video analysis (RVA) during the first two years of life. Electronic databases were systematically searched and a total of 23 studies were selected. These studies were then categorised according to whether children were later diagnosed with ASD (13 studies), RTT (8 studies), or FXS (2 studies), and then described in terms of (a) participant characteristics, (b) control group characteristics, (c) video footage, (d) behaviours analysed, and (e) main findings. This overview supports the use of RVA in analysing the early development of vocalisations in children later diagnosed with ASD, RTT or FXS, and provides an in-depth analysis of vocalisation presentation, complex vocalisation production, and the rate and/or frequency of vocalisation production across the three disorders. Implications are discussed in terms of extending crude vocal analyses to more precise methods that might provide more powerful means by which to discriminate between disorders during early development. A greater understanding of the early manifestation of these disorders may then lead to improvements in earlier detection.

Social experience affects neuronal responses to male calls in adult female zebra finches.

PubMed

Menardy, F; Touiki, K; Dutrieux, G; Bozon, B; Vignal, C; Mathevon, N; Del Negro, C

2012-04-01

Plasticity studies have consistently shown that behavioural relevance can change the neural representation of sounds in the auditory system, but what occurs in the context of natural acoustic communication where significance could be acquired through social interaction remains to be explored. The zebra finch, a highly social songbird species that forms lifelong pair bonds and uses a vocalization, the distance call, to identify its mate, offers an opportunity to address this issue. Here, we recorded spiking activity in females while presenting distance calls that differed in their degree of familiarity: calls produced by the mate, by a familiar male, or by an unfamiliar male. We focused on the caudomedial nidopallium (NCM), a secondary auditory forebrain region. Both the mate's call and the familiar call evoked responses that differed in magnitude from responses to the unfamiliar call. This distinction between responses was seen both in single unit recordings from anesthetized females and in multiunit recordings from awake freely moving females. In contrast, control females that had not heard them previously displayed responses of similar magnitudes to all three calls. In addition, more cells showed highly selective responses in mated than in control females, suggesting that experience-dependent plasticity in call-evoked responses resulted in enhanced discrimination of auditory stimuli. Our results as a whole demonstrate major changes in the representation of natural vocalizations in the NCM within the context of individual recognition. The functional properties of NCM neurons may thus change continuously to adapt to the social environment. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

GnRH-agonist implants suppress reproductive function and affects ovarian LHR and FSHR expression in prepubertal female cats.

PubMed

Mehl, N S; Srisuwatanasagul, S; Swangchan-Uthai, T; Sirivaidyapong, S; Khalid, M

2017-01-01

Effect of a GnRH-agonist (deslorelin) was studied on reproductive function and ovarian luteinizing hormone receptor (LHR) and follicle stimulating hormone receptor (FSHR) expression in prepubertal female cats that were either implanted with 4.7-mg deslorelin (implanted: n = 6) or not (controls: n = 18) or ovariohysterectomized at prepubertal age (prepubertal OVH: n = 6). Body weights, fecal estradiol, and sexual behavior of implanted and control cats were monitored for 48 weeks followed by collection of ovaries and uteri. Ovaries and uteri were collected from control cats at follicular, luteal, and inactive stage (n = 6/group) and from prepubertal OVH cats at prepubertal age. Ovaries and uteri were analyzed for anatomical/histological characteristics. Ovaries were also analyzed for LHR and FSHR expression. Statistical analysis showed higher (P ≤ 0.05) body weight in control than implanted cats only during 22nd to 26th weeks of the study. Estrus was observed in control cats only. Deslorelin reduced (P ≤ 0.05) ovarian weight and number of antral follicles but did not affect endometrial thickness and gland diameter. However, myometrial thickness of implanted cats was significantly lower than control cats at follicular and luteal stage. Ovarian LHR mRNA expression was lower (P ≤ 0.05) in implanted cats than control cats at follicular stage. FSHR mRNA and LHR protein expression did not differ among the three groups. FSHR protein expression was lower (P ≤ 0.05) in prepubertal OVH cats and was not affected by deslorelin. In conclusion, deslorelin suppresses reproductive function in prepubertal female cats for at least 48 weeks possibly through a change in the ovarian mRNA expression of LHR. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical features and gene mutational spectrum of CDKL5-related diseases in a cohort of Chinese patients

PubMed Central

2014-01-01

Background Mutations in the cyclin-dependent kinase-like 5 (CDKL5) (NM_003159.2) gene have been associated with early-onset epileptic encephalopathies or Hanefeld variants of RTT(Rett syndrome). In order to clarify the CDKL5 genotype-phenotype correlations in Chinese patients, CDKL5 mutational screening in cases with early-onset epileptic encephalopathies and RTT without MECP2 mutation were performed. Methods The detailed clinical information including clinical manifestation, electroencephalogram (EEG), magnetic resonance imaging (MRI), blood, urine amino acid and organic acid screening of 102 Chinese patients with early-onset epileptic encephalopathies and RTT were collected. CDKL5 gene mutations were analyzed by PCR, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). The patterns of X-chromosome inactivation (XCI) were studied in the female patients with CDKL5 gene mutation. Results De novo CDKL5 gene mutations were found in ten patients including one missense mutation (c.533G > A, p.R178Q) which had been reported, two splicing mutations (ISV6 + 1A > G, ISV13 + 1A > G), three micro-deletions (c.1111delC, c.2360delA, c.234delA), two insertions (c.1791 ins G, c.891_892 ins TT in a pair of twins) and one nonsense mutation (c.1375C > T, p.Q459X). Out of ten patients, 7 of 9 females with Hanefeld variants of RTT and the remaining 2 females with early onset epileptic encephalopathy, were detected while only one male with infantile spasms was detected. The common features of all female patients with CDKL5 gene mutations included refractory seizures starting before 4 months of age, severe psychomotor retardation, Rett-like features such as hand stereotypies, deceleration of head growth after birth and poor prognosis. In contrast, the only one male patient with CDKL5 mutation showed no obvious Rett-like features as females in our cohort. The X-chromosome inactivation patterns of all the female patients were random. Conclusions Mutations in CDKL

Clinical features and gene mutational spectrum of CDKL5-related diseases in a cohort of Chinese patients.

PubMed

Zhao, Ying; Zhang, Xiaoying; Bao, Xinhua; Zhang, Qingping; Zhang, Jingjing; Cao, Guangna; Zhang, Jie; Li, Jiarui; Wei, Liping; Pan, Hong; Wu, Xiru

2014-02-25

Mutations in the cyclin-dependent kinase-like 5 (CDKL5) (NM_003159.2) gene have been associated with early-onset epileptic encephalopathies or Hanefeld variants of RTT(Rett syndrome). In order to clarify the CDKL5 genotype-phenotype correlations in Chinese patients, CDKL5 mutational screening in cases with early-onset epileptic encephalopathies and RTT without MECP2 mutation were performed. The detailed clinical information including clinical manifestation, electroencephalogram (EEG), magnetic resonance imaging (MRI), blood, urine amino acid and organic acid screening of 102 Chinese patients with early-onset epileptic encephalopathies and RTT were collected. CDKL5 gene mutations were analyzed by PCR, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). The patterns of X-chromosome inactivation (XCI) were studied in the female patients with CDKL5 gene mutation. De novo CDKL5 gene mutations were found in ten patients including one missense mutation (c.533G > A, p.R178Q) which had been reported, two splicing mutations (ISV6 + 1A > G, ISV13 + 1A > G), three micro-deletions (c.1111delC, c.2360delA, c.234delA), two insertions (c.1791 ins G, c.891_892 ins TT in a pair of twins) and one nonsense mutation (c.1375C > T, p.Q459X). Out of ten patients, 7 of 9 females with Hanefeld variants of RTT and the remaining 2 females with early onset epileptic encephalopathy, were detected while only one male with infantile spasms was detected. The common features of all female patients with CDKL5 gene mutations included refractory seizures starting before 4 months of age, severe psychomotor retardation, Rett-like features such as hand stereotypies, deceleration of head growth after birth and poor prognosis. In contrast, the only one male patient with CDKL5 mutation showed no obvious Rett-like features as females in our cohort. The X-chromosome inactivation patterns of all the female patients were random. Mutations in CDKL5 gene are responsible for 7 with

Parenting characteristics of female caregivers of children affected by chronic endocrine conditions: a comparison between disorders of sex development and type 1 diabetes mellitus.

PubMed

Kirk, Katherine D; Fedele, David A; Wolfe-Christensen, Cortney; Phillips, Timothy M; Mazur, Tom; Mullins, Larry L; Chernausek, Steven D; Wisniewski, Amy B

2011-12-01

Rearing a child with a chronic illness is stressful and can potentially affect parenting style, which may result in poorer outcomes for children. The purpose of this study was to compare parenting characteristics of female caregivers rearing children with a disorder of sex development (DSD) to female caregivers rearing children with type 1 diabetes mellitus (T1DM). Caregivers of both groups were matched according to age and compared on measures of stress and parenting practices. Both groups demonstrated significant levels of stress and negative parenting practices. Children with T1DM and male children with non-life-threatening DSD were perceived as more vulnerable by their caregivers. Better understanding of parenting experiences of female caregivers rearing children with DSD, particularly male children, will facilitate the development of individualized interventions to ameliorate negative parenting practices and stress, with the long-term goal of improved health outcomes for their children. Copyright © 2011 Elsevier Inc. All rights reserved.

Factors Affecting Choice, Satisfaction, and Success in the Female Self-Employed.

ERIC Educational Resources Information Center

Waddell, Frederick T.

1983-01-01

Compared female business owners, managers, and secretaries to examine predictors of occupational choice, satisfaction, and success in the self-employment of women. Results showed owners rated higher than secretaries in achievement motivation, locus of control, and sex role, while owners and managers were similar except in parental models. (JAC)

The disruption of central CO2 chemosensitivity in a mouse model of Rett syndrome

PubMed Central

Zhang, Xiaoli; Su, Junda; Cui, Ningren; Gai, Hongyu; Wu, Zhongying

2011-01-01

People with Rett syndrome (RTT) have breathing instability in addition to other neuropathological manifestations. The breathing disturbances contribute to the high incidence of unexplained death and abnormal brain development. However, the cellular mechanisms underlying the breathing abnormalities remain unclear. To test the hypothesis that the central CO2 chemoreception in these people is disrupted, we studied the CO2 chemosensitivity in a mouse model of RTT. The Mecp2-null mice showed a selective loss of their respiratory response to 1–3% CO2 (mild hypercapnia), whereas they displayed more regular breathing in response to 6–9% CO2 (severe hypercapnia). The defect was alleviated with the NE uptake blocker desipramine (10 mg·kg−1·day−1 ip, for 5–7 days). Consistent with the in vivo observations, in vitro studies in brain slices indicated that CO2 chemosensitivity of locus coeruleus (LC) neurons was impaired in Mecp2-null mice. Two major neuronal pH-sensitive Kir currents that resembled homomeric Kir4.1 and heteromeric Ki4.1/Kir5.1 channels were identified in the LC neurons. The screening of Kir channels with real-time PCR indicated the overexpression of Kir4.1 in the LC region of Mecp2-null mice. In a heterologous expression system, an overexpression of Kir4.1 resulted in a reduction in the pH sensitivity of the heteromeric Kir4.1-Kir5.1 channels. Given that Kir4.1 and Kir5.1 subunits are also expressed in brain stem respiration-related areas, the Kir4.1 overexpression may not allow CO2 to be detected until hypercapnia becomes severe, leading to periodical hyper- and hypoventilation in Mecp2-null mice and, perhaps, in people with RTT as well. PMID:21307341

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.

Female sexual dysfunction in female genital mutilation.

PubMed

Elneil, Sohier

2016-01-01

Female genital mutilation (FGM), otherwise known as female genital cutting (FGC), is currently very topical and has become a significant global political issue. The impact of FGM on the lives of women and girls is enormous, as it often affects both their psychology and physical being. Among the complications that are often under-reported and not always acknowledged is female sexual dysfunction (FSD). FSD presents with a complex of symptoms including lack of libido, arousability and orgasm. This often occurs in tandem with chronic urogenital pain and anatomical disruption due to perineal scarring.To treat FSD in FGM each woman needs specifically directed holistic care, geared to her individual case. This may include psychological support, physiotherapy and, on occasion, reconstructive surgery. In many cases the situation is complicated by symptoms of chronic pelvic pain, which can make treatment increasingly difficult as this issue needs a defined multidisciplinary approach for its effective management in its own right. The problems suffered by women with FGM are wholly preventable, as the practice need not happen. The current global momentum to address the social, cultural, economic and medical issues of FGM is being supported by communities, governments, non-governmental agencies (NGOs) and healthcare providers. It is only by working together that the practice can be abolished and women and girls may be free from this practice and its associated consequences. © The Author(s) 2016.

Female major histocompatibility complex type affects male testosterone levels and sperm number in the horse (Equus caballus)

PubMed Central

Burger, D.; Dolivo, G.; Marti, E.; Sieme, H.; Wedekind, C.

2015-01-01

Odours of vertebrates often contain information about the major histocompatibility complex (MHC), and are used in kin recognition, mate choice or female investment in pregnancy. It is, however, still unclear whether MHC-linked signals can also affect male reproductive strategies. We used horses (Equus caballus) to study this question under experimental conditions. Twelve stallions were individually exposed either to an unfamiliar MHC-similar mare and then to an unfamiliar MHC-dissimilar mare, or vice versa. Each exposure lasted over a period of four weeks. Peripheral blood testosterone levels were determined weekly. Three ejaculates each were collected in the week after exposure to both mares (i.e. in the ninth week) to determine mean sperm number and sperm velocity. We found high testosterone levels when stallions were kept close to MHC-dissimilar mares and significantly lower ones when kept close to MHC-similar mares. Mean sperm number per ejaculate (but not sperm velocity) was positively correlated to mean testosterone levels and also affected by the order of presentation of mares: sperm numbers were higher if MHC-dissimilar mares were presented last than if MHC-similar mares were presented last. We conclude that MHC-linked signals influence testosterone secretion and semen characteristics, two indicators of male reproductive strategies. PMID:25904670

Pharmacological Stimulation of the Brain Serotonin Receptor 7 as a Novel Therapeutic Approach for Rett Syndrome

PubMed Central

De Filippis, Bianca; Nativio, Paola; Fabbri, Alessia; Ricceri, Laura; Adriani, Walter; Lacivita, Enza; Leopoldo, Marcello; Passarelli, Francesca; Fuso, Andrea; Laviola, Giovanni

2014-01-01

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG-binding protein 2 gene (MECP2) cause >95% of classic cases, and currently there is no cure for this devastating disorder. The serotonin receptor 7 (5-HT7R) is linked to neuro-physiological regulation of circadian rhythm, mood, cognition, and synaptic plasticity. We presently report that 5-HT7R density is consistently reduced in cortical and hippocampal brain areas of symptomatic MeCP2–308 male mice, a RTT model. Systemic repeated treatment with LP-211 (0.25 mg/kg once/day for 7 days), a brain-penetrant selective 5-HT7R agonist, was able to rescue RTT-related defective performance: anxiety-related profiles in a Light/Dark test, motor abilities in a Dowel test, the exploratory behavior in the Marble Burying test, as well as memory in the Novelty Preference task. In the brain of RTT mice, LP-211 also reversed the abnormal activation of PAK and cofilin (key regulators of actin cytoskeleton dynamics) and of the ribosomal protein (rp) S6, whose reduced activation in MECP2 mutant neurons by mTOR is responsible for the altered protein translational control. Present findings indicate that pharmacological targeting of 5-HT7R improves specific behavioral and molecular manifestations of RTT, thus representing a first step toward the validation of an innovative systemic treatment. Beyond RTT, the latter might be extended to other disorders associated with intellectual disability. PMID:24809912

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.

Female urinary incontinence and sexuality

PubMed Central

Mota, Renato Lains

2017-01-01

ABSTRACT Urinary incontinence is a common problem among women and it is estimated that between 15 and 55% of them complain of lower urinary symptoms. The most prevalent form of urinary incontinence is associated with stress, followed by mixed urinary incontinence and urge urinary incontinence. It is a symptom with several effects on quality of life of women mainly in their social, familiar and sexual domains. Female reproductive and urinary systems share anatomical structures, which promotes that urinary problems interfere with sexual function in females. This article is a review of both the concepts of female urinary incontinence and its impact on global and sexual quality of life. Nowadays, it is assumed that urinary incontinence, especially urge urinary incontinence, promotes anxiety and several self-esteem damages in women. The odour and the fear of incontinence during sexual intercourse affect female sexual function and this is related with the unpredictability and the chronicity of incontinence, namely urge urinary incontinence. Female urinary incontinence management involves conservative (pelvic floor muscle training), surgical and pharmacological treatment. Both conservative and surgical treatments have been studied about its benefit in urinary incontinence and also the impact among female sexual function. Unfortunately, there are sparse articles that evaluate the benefits of female sexual function with drug management of incontinence. PMID:28124522

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

Sex and Gender: How Being Male or Female Can Affect Your Health

MedlinePlus

... Special Issues Subscribe May 2016 Print this issue Sex and Gender How Being Male or Female Can ... a major impact on your health. While both sexes are similar in many ways, researchers have found ...

Perfectionism, Performance, and State Positive Affect and Negative Affect after a Classroom Test

ERIC Educational Resources Information Center

Flett, Gordon L.; Blankstein, Kirk R.; Hewitt, Paul L.

2009-01-01

The current study examined the associations among trait dimensions of perfectionism, test performance, and levels of positive and negative affect after taking a test. A sample of 92 female university students completed the Multidimensional Perfectionism Scale one week prior to an actual class test. Measures of positive affect and negative affect…

Clinical factors affecting physicians' management decisions in cases of female partner abuse.

PubMed

Ferris, L E; Norton, P; Dunn, E V; Gort, E H

1999-06-01

This study determined which clinical factors influence Canadian primary care physicians' management decisions in cases of female partner abuse. We used a cross-sectional survey design and randomly sampled (n = 2,014) English-speaking Canadian physicians with a primary interest in family or general practice who were practicing in any of the 12 provinces and territories in Canada and who were active in private practice and registered to prescribe. Respondents completed a questionnaire that required them to score management decision plans in response to case scenarios illustrating typical office-based situations that might involve domestic violence. The response rate was 50.7% (n = 1,022). Using forward stepwise regression analysis, the strongest predictor of whether a physician endorsed a management plan in response to violence was whether the woman acknowledged or revealed the abuse. Male physicians were more likely than females to endorse talking with the suspected abuser if he was known to them, regardless of the quality of this patient-physician relationship with the abuser. Decisions about whether to deal with the abuse or the selection of a management plan are not dependent on the severity of the physical abuse and the emotional consequences. Whether a woman acknowledges or reveals the abuse, as well as whether both the male and female patients are in the physician's practice, are predictive of whether a physician's response to a case scenario involves dealing with spousal abuse and how he/she will address it.

Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits.

PubMed

Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

2015-01-01

Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis.

Family affection as a protective factor against the negative effects of perceived Asian values gap on the parent-child relationship for Asian American male and female college students.

PubMed

Park, Yong S; Vo, Leyna P; Tsong, Yuying

2009-01-01

The study examined whether family affection (i.e., affective responsiveness, affectionate communication, and affective orientation) protected against the negative effects of perceived parent-child Asian values gap on the quality of their parent relationships for 259 female and 77 male Asian American college students. Asian values gap was higher for women than men, and inversely related to a perceived healthy parent-child relationship for both genders. Participants rated the relationship with their mothers as more positive and affectionate than with their fathers. Both parents were reported to communicate more supportive affection than verbal and nonverbal affection. Affective responsiveness was identified as a protective factor in the father-son relationship whereas verbal affection protected the mother-daughter relationship. The study also revealed that daughters' affective orientation had beneficial effects on the father-daughter relationship at lower levels of Asian values gap. Clinical implications and directions for future research are discussed.

The impact of having a sibling with an intellectual disability: parental perspectives in two disorders.

PubMed

Mulroy, S; Robertson, L; Aiberti, K; Leonard, H; Bower, C

2008-03-01

The potential effects on other children when there is a child with intellectual disability (ID) in the family are being increasingly recognized. This study describes the impact of having a sibling with Down syndrome or Rett syndrome using a questionnaire completed by parents. The parents of 186 Western Australian children with Down syndrome and 141 Australian girls and women with Rett syndrome participated in the study. Patterns of reporting disadvantages and/or benefits were compared across a number of child and family variables (age, functional ability and birth order of the affected child, number of siblings and number of parents in the family home) and by socio-economic status as measured by the index of relative socio-economic disadvantage and by area of residence. Parents' responses to open-ended questions about the benefits and/or disadvantages for siblings of their child were analysed for themes. The majority of parents in the Rett syndrome and Down syndrome groups reported both disadvantages and benefits for siblings. In the Rett syndrome group, families from outer regional areas were the least likely to mention disadvantages and those with a smaller family more likely to note disadvantages. In both groups, more socio-economically advantaged families were more likely to report disadvantages. In the Down syndrome group, benefits were also more commonly reported by parents who were socio-economically advantaged, and by larger and two-parent families. Major disadvantages for siblings centred around parental and personal time constraints, relationships and socializing, restrictions, parental emotion and burden of helping. Major benefits were related to personality characteristics. Parents identified both benefits and disadvantages to the siblings of their child with either Rett syndrome or Down syndrome. It is important that these findings are incorporated into any discussion around the impact on the family of a child diagnosed with an ID.

Predicting the Effects of Comparable Worth Programs on Female Labor Supply.

ERIC Educational Resources Information Center

Nakamura, Alice; Nakamura, Masao

1989-01-01

Surveys theories in labor economics about how the female labor supply is affected by the wage offers that women receive. Summarizes the implications concerning expected effects of comparable worth wage adjustments on female labor supply. Examines empirical evidence pertaining to the theory of female labor supply. (JS)

DESCRIBING LYMPHEDEMA IN FEMALES WITH TURNER SYNDROME.

PubMed

Rothbauer, J; Driver, S; Callender, L

2015-09-01

Turner syndrome (TS) is a chromosomal condition affecting an estimated 1 in 2,500 girls where the second X chromosome is missing, or partially formed. This abnormality affects multiple body systems and can lead to short stature, cardiac, neural, and renal abnormalities. Due to the chronic, non-life threatening nature of lymphedema in comparison to other symptoms of TS, it is often ignored by girls and women with TS and their physicians. Consequently, little is known about how lymphedema affects girls and women with TS across the lifespan. Therefore, the objective of the study was to deliver an online survey for females with TS and caregivers in the US, UK, and Canada to provide a worldwide perspective on their current experience with lymphedema within the spectrum of TS. There were 219 participants who completed the survey, and we were able to identify incidence and characteristics of lymphedema across the lifespan. In addition, we found that females with 45,X karyotyping were more likely to report lymphedema symptoms. Lymphedema is not the most significant concern of females with TS, but education, physician evaluation, and assistance with referrals for treatment and management would improve the ease of managing lymphedema in girls and women with TS.

MECP2 variation in Rett syndrome-An overview of current coverage of genetic and phenotype data within existing databases.

PubMed

Townend, Gillian S; Ehrhart, Friederike; van Kranen, Henk J; Wilkinson, Mark; Jacobsen, Annika; Roos, Marco; Willighagen, Egon L; van Enckevort, David; Evelo, Chris T; Curfs, Leopold M G

2018-04-27

Rett syndrome (RTT) is a monogenic rare disorder that causes severe neurological problems. In most cases, it results from a loss-of-function mutation in the gene encoding methyl-CPG-binding protein 2 (MECP2). Currently, about 900 unique MECP2 variations (benign and pathogenic) have been identified and it is suspected that the different mutations contribute to different levels of disease severity. For researchers and clinicians, it is important that genotype-phenotype information is available to identify disease-causing mutations for diagnosis, to aid in clinical management of the disorder, and to provide counseling for parents. In this study, 13 genotype-phenotype databases were surveyed for their general functionality and availability of RTT-specific MECP2 variation data. For each database, we investigated findability and interoperability alongside practical user functionality, and type and amount of genetic and phenotype data. The main conclusions are that, as well as being challenging to find these databases and specific MECP2 variants held within, interoperability is as yet poorly developed and requires effort to search across databases. Nevertheless, we found several thousand online database entries for MECP2 variations and their associated phenotypes, diagnosis, or predicted variant effects, which is a good starting point for researchers and clinicians who want to provide, annotate, and use the data. © 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc.

Identification of female-specific QTLs affecting an emotionality-related behavior in rats.

PubMed

Ramos, A; Moisan, M P; Chaouloff, F; Mormède, C; Mormède, P

1999-09-01

The influence of genetic factors on psychological traits and disorders has been repeatedly demonstrated; however, the molecular mechanisms underlying such an influence remain largely unknown. Anxiety-related disorders constitute the most common class of mental disorder in humans, with women being diagnosed far more frequently than men. A better understanding of the genetic and gender-related mechanisms mediating anxiety traits should enable the development of more rational methods for preventing and treating anxiety disorders. In this study we have aimed to identify, for the first time, quantitative trait loci (QTL) influencing anxiety/emotionality-related traits in rats. To this end, two strains-Lewis (LEW) and Spontaneously Hypertensive Rats (SHR)-that differ for several behavioral measures of anxiety/emotionality were intercrossed. A QTL analysis of the F2 population revealed suggestive loci for various traits, including behaviors in the elevated plus-maze and blood pressure. In addition, one major QTL explaining 50.4% of the total variance (LOD = 7.22) was identified on chromosome 4 for the locomotion in the central and aversive area of the open field. Two other relevant QTLs have been recently mapped near this chromosomic region in the rat, which also harbors Tac1r, the gene encoding for the substance P receptor. Our major QTL affected females but not males and its effect depended on the type of cross (LEW or SHR grandmothers). The present results reveal a complex genetic basis underlying emotional behaviors and they confirm the existence of interactions between genetic factors and sex for this kind of trait. Further investigation of the loci identified herein may give clues to the pathophysiology of psychiatric disorders such as anxiety-related ones.

Female genital mutilation.

PubMed

Ladjali, M; Rattray, T W; Walder, R J

1993-08-21

Female genital mutilation, also misleadingly known as female circumcision, is usually performed on girls ranging in from 1 week to puberty. Immediate physical complications include severe pain, shock, infection, bleeding, acute urinary infection, tetanus, and death. Longterm problems include chronic pain, difficulties with micturition and menstruation, pelvic infection leading to infertility, and prolonged and obstructed labor during childbirth. An estimated 80 million girls and women have undergone female genital mutilation. In Britain alone an estimated 10,000 girls are currently at risk. Religious, cultural, medical, and moral grounds rationalize the custom which is practiced primarily in sub-Saharan Africa, the Arab world, Malaysia, Indonesia, and among migrant populations in Western countries. According to WHO it is correlated with poverty, illiteracy, and the low status of women. Women who escape mutilation are not sought in marriage. WHO, the UN Population Fund, the UN Children's Fund, the International Planned Parenthood Federation, and the UN Convention on the Rights of the Child have issued declarations on the eradication of female genital mutilation. In Britain, local authorities have intervened to prevent parents from mutilating their daughters. In 1984, the Inter-African Committee Against Harmful Traditional Practices Affecting Women and Children was established to work toward eliminating female genital mutilation and other damaging customs. National committees in 26 African countries coordinate projects run by local people using theater, dance, music, and storytelling for communication. In Australia, Canada, Europe, and the US women have organized to prevent the practice among vulnerable migrants and refugees.

Sabotaging Our Sisters: Perceptions of Female Relational Aggression in Higher Education among Female Faculty and Administrators at Three Western U.S. Universities

ERIC Educational Resources Information Center

Nyborg, Deborah G.

2012-01-01

The purpose of this study was to explore and understand relational workplace aggression among female faculty and administrators at three western U.S. universities. This study was designed to address the gap in empirical knowledge of the phenomenon by elucidating how workplace relational aggression affects the lives of female university faculty and…

Evaluation of the Relationship between Critical Thinking Skills and Affective Control in Child Training Students of the Female Technical and Vocational College in the City of Broujerd

ERIC Educational Resources Information Center

Esmaeili, Zohreh; Bagheri, Mahdi

2015-01-01

This study is a descriptive-correlational study with the purpose of evaluating the relationship between critical thinking skills and affective control in child training students of the female technical and Vocational College in the city of Broujerd. Statistical population of this study consisted of all students in the field of child training of…

Low bone mineral mass is associated with decreased bone formation and diet in girls with Rett syndrome.

PubMed

Motil, Kathleen J; Barrish, Judy O; Neul, Jeffrey L; Glaze, Daniel G

2014-09-01

The aim of the present study was to characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of girls with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Total body bone mineral content (BMC) and bone mineral density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and sex, showed significant positive associations with total body BMD z scores. The present study suggests decreased bone formation instead of increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium, and phosphorus intakes may offer an opportunity to improve bone health in RTT.

Menstrual Cycle Effects on Anaerobic Power, Muscular Strength, and Muscular Endurance in Trained and Untrained Females.

ERIC Educational Resources Information Center

Rosenburg, Beth S.; And Others

A study determined if anaerobic power, isometric strength, and isometric endurance are affected by the menstrual cycle and if endurance trained females and untrained females are affected in the same manner on these performance parameters. Subjects were healthy, normally menstruating females, ages 18-34 years who were classified as either trained…

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

RSRC1 mutation affects intellect and behaviour through aberrant splicing and transcription, downregulating IGFBP3.

PubMed

Perez, Yonatan; Menascu, Shay; Cohen, Idan; Kadir, Rotem; Basha, Omer; Shorer, Zamir; Romi, Hila; Meiri, Gal; Rabinski, Tatiana; Ofir, Rivka; Yeger-Lotem, Esti; Birk, Ohad S

2018-04-01

RSRC1, whose polymorphism is associated with altered brain function in schizophrenia, is a member of the serine and arginine rich-related protein family. Through homozygosity mapping and whole exome sequencing we show that RSRC1 mutation causes an autosomal recessive syndrome of intellectual disability, aberrant behaviour, hypotonia and mild facial dysmorphism with normal brain MRI. Further, we show that RSRC1 is ubiquitously expressed, and that the RSRC1 mutation triggers nonsense-mediated mRNA decay of the RSRC1 transcript in patients' fibroblasts. Short hairpin RNA (shRNA)-mediated lentiviral silencing and overexpression of RSRC1 in SH-SY5Y cells demonstrated that RSRC1 has a role in alternative splicing and transcription regulation. Transcriptome profiling of RSRC1-silenced cells unravelled specific differentially expressed genes previously associated with intellectual disability, hypotonia and schizophrenia, relevant to the disease phenotype. Protein-protein interaction network modelling suggested possible intermediate interactions by which RSRC1 affects gene-specific differential expression. Patient-derived induced pluripotent stem cells, differentiated into neural progenitor cells, showed expression dynamics similar to the RSRC1-silenced SH-SY5Y model. Notably, patient neural progenitor cells had 9.6-fold downregulated expression of IGFBP3, whose brain expression is affected by MECP2, aberrant in Rett syndrome. Interestingly, Igfbp3-null mice have behavioural impairment, abnormal synaptic function and monoaminergic neurotransmission, likely correlating with the disease phenotype.

A mutation-led search for novel functional domains in MeCP2.

PubMed

Guy, Jacky; Alexander-Howden, Beatrice; FitzPatrick, Laura; DeSousa, Dina; Koerner, Martha V; Selfridge, Jim; Bird, Adrian

2018-04-27

Most missense mutations causing Rett syndrome affect domains of MeCP2 that have been shown to either bind methylated DNA or interact with a transcriptional co-repressor complex. Several mutations, however, including the C-terminal truncations that account for ∼10% of cases, fall outside these characterised domains. We studied the molecular consequences of four of these "non-canonical" mutations in cultured neurons and mice to see if they reveal additional essential domains without affecting known properties of MeCP2. The results show that the mutations partially or strongly deplete the protein and also in some cases interfere with co-repressor recruitment. These mutations therefore impact the activity of known functional domains and do not invoke new molecular causes of Rett syndrome. The finding that a stable C-terminal truncation does not compromise MeCP2 function raises the possibility that small molecules which stabilise these mutant proteins may be of therapeutic value.

Mutation screening of the CDKL5 gene in cryptogenic infantile intractable epilepsy and review of clinical sensitivity.

PubMed

Intusoma, Utcharee; Hayeeduereh, Fadell; Plong-On, Oradawan; Sripo, Thanya; Vasiknanonte, Punnee; Janjindamai, Supachai; Lusawat, Apasri; Thammongkol, Sasipa; Visudtibhan, Anannit; Limprasert, Pornprot

2011-09-01

To perform CDKL5 mutation screening in Thai children with cryptogenic infantile intractable epilepsy and to determine the clinical sensitivity of CDKL5 screening when different inclusion criteria were applied. Children with cryptogenic infantile intractable epilepsy were screened for CDKL5 mutation using multiplex ligation-dependent probe amplification and DNA sequencing. The clinical sensitivity was reviewed by combining the results of studies using similar inclusion screening criteria. Thirty children (19 girls and 11 boys) with a median seizure onset of 7 months were screened. Almost a half had infantile spasms and one fifth had stereotypic hand movements. A novel c.2854C>T (p.R952X) was identified in an ambulatory girl who had severe mental retardation, multiple types of seizures without Rett-like features. Her mother had a mild intellectual disability, yet her grandmother and half sister were normal despite having the same genetic alteration (random X-inactivation patterns). The pathogenicity of p.R952X identified here was uncertain since healthy relatives and 6 female controls also harbor this alteration. The clinical sensitivity of CDKL5 mutation screening among females with Rett-like features and negative MECP2 screening was 7.8% while the clinical sensitivity among females having cryptogenic intractable seizures with an onset before the ages of 12, 6 and 3 months were 4.7, 11.6 and 14.3%, respectively. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Male/Female Differential Encoding and Intercultural Differential Decoding of Nonverbal Affective Communication.

ERIC Educational Resources Information Center

St. Martin, Gail McAllister

In order to investigate the process of nonverbal communication of emotions in a simulated intercultural context, videotapes were made in which two white Americans (one male and one female) responded to paragraphs which evoked the following emotions: sadness, disgust, anger, surprise, happiness, and fear. These portrayals were then viewed by male…

Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits

PubMed Central

Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

2015-01-01

Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis. PMID:26175757

Lecture versus DVD and Attitude Change toward Female Masturbation

ERIC Educational Resources Information Center

Keels, Megan; Lee, Zoey; Knox, David; Wilson, Ken

2013-01-01

Four-hundred and ninety eight female undergraduate students at a large southeastern university participated in a study to assess how lecture versus DVD format affected attitude change towards female masturbation. All groups were given a pre and post test to assess masturbatory attitudes. Group 1 experienced a masturbation lecture. Group 2…

An Analysis of Female Research Productivity in Nigerian Universities

ERIC Educational Resources Information Center

Ogbogu, Christiana O.

2009-01-01

This study examines the research output of female staff and the factors that affect their research productivity in the Nigerian university system. The study was carried out with a view to promoting strategies that will enhance productivity and increase the research output of female staff in Nigerian universities. The study adopted a survey…

Exposure to altered gravity during specific developmental periods differentially affects growth, development, the cerebellum and motor functions in male and female rats

NASA Astrophysics Data System (ADS)

Nguon, K.; Ladd, B.; Sajdel-Sulkowska, E. M.

2006-01-01

We previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that neonatal cerebellar structure and motor coordination may be particularly vulnerable to the effects of hypergravity during specific developmental stages. To test this hypothesis, we compared neurodevelopment, motor behavior and cerebellar structure in rat neonates exposed to 1.65 G on a 24-ft centrifuge during discrete periods of time: the 2nd week of pregnancy [gestational day (G) 8 through G15; group A], the 3rd week of pregnancy (G15 through birth on G22/G23; group B), the 1st week of nursing [birth through postnatal day (P) 6; group C], the 2nd and 3rd weeks of nursing (P6 through P21; group D), the combined 2nd and 3rd weeks of pregnancy and nursing (G8 through P21; group E) and stationary control (SC) neonates (group F). Prenatal exposure to hypergravity resulted in intrauterine growth retardation as reflected by a decrease in the number of pups in a litter and lower average mass at birth. Exposure to hypergravity immediately after birth impaired the righting response on P3, while the startle response in both males and females was most affected by exposure during the 2nd and 3rd weeks after birth. Hypergravity exposure also impaired motor functions, as evidenced by poorer performance on a rotarod; while both males and females exposed to hypergravity during the 2nd and 3rd weeks after birth performed poorly on P21, male neonates were most dramatically affected by exposure to hypergravity during the second week of gestation, when the duration of their recorded stay on the rotarod was one half that of SC males. Cerebellar mass was most reduced by later postnatal exposure. Thus, for the developing rat cerebellum, the postnatal period that overlaps the brain growth spurt is the most vulnerable to hypergravity. However, male motor behavior is also affected by midpregnancy exposure to

Issues unique to the female runner.

PubMed

Prather, Heidi; Hunt, Deyvani

2005-08-01

Care and treatment of female runners will improve as further knowledge regarding the unique factors that affect them becomes available. For care and treatment to be their most effective, current and recent information needs to be disseminated among health care providers, coaches, teachers, school administrators, and parents. In young athletes, peer support and education are the most important factors in the success of detection and treatment. Individuals who have the female athlete triad are at significant risk for stress fractures and other injuries. Early detection and multidisciplinary treatment should begin after fractures are detected to reduce or prevent long-term adverse sequelae to bone. In addition, correction of menstrual dysfunction can help to prevent later fertility problems. Addressing the unique biomechanics and core strength of female runners also is essential to rehabilitate athletes past symptom resolution. A thorough understanding of the unique issues for female runners is essential for the prevention of injuries and plays an important role in the promotion of female participation in recreational and competitive running.

Differences in job stress experienced by female and male Japanese psychiatric nurses.

PubMed

Yada, Hironori; Abe, Hiroshi; Omori, Hisamitsu; Matsuo, Hisae; Masaki, Otsubo; Ishida, Yasushi; Katoh, Takahiko

2014-10-01

In psychiatric nursing, female nurses tend to spend more time building rapport with patients and developing cooperative working relationships with colleagues; they encounter more sexual harassment by patients. In contrast, male nurses respond to aggressive patients and tend to resist physically caring for female patients; they encounter more physical and verbal assault from patients. These gender differences might result in differences in job-related stress. We quantitatively examined gender differences in psychiatric nurses' job stress. The Psychiatric Nurse Job Stressor Scale and the Stress Reaction Scale of the Brief Job Stress Questionnaire were administered to 159 female and 85 male Japanese psychiatric nurses. The results indicated that female nurses had significantly higher stress levels than males related to psychiatric nursing ability, attitude towards nursing, and stress reactions of fatigue and anxiety. Moreover, the factors affecting stress reactions differed somewhat between sexes. In particular, male nurses reported that greater irritability was affected by patients' attitudes. Their anxiety and somatic symptoms were affected by their attitude towards nursing, and depressed mood was affected by psychiatric nursing ability. Knowledge of these differences can lead to better mental health-care interventions for psychiatric nurses. © 2014 Australian College of Mental Health Nurses Inc.

Dysmenorrhea Characteristics of Female Students of Health School and Affecting Factors and Their Knowledge and Use of Complementary and Alternative Medicine Methods.

PubMed

Midilli, Tulay Sagkal; Yasar, Eda; Baysal, Ebru

2015-01-01

The purpose of this study was to examine the menstruation and dysmenorrhea characteristics and the factors affecting dysmenorrhea of health school students, and the knowledge and use of the methods of complementary and alternative medicine (CAM) on the part of those students with dysmenorrhea. This is a descriptive study. A descriptive analysis was made by calculating the number, percentage, mean, Pearson χ, and logistic regression analysis. A total of 488 female students participated in the research and 87.7% (n = 428) of all students experienced dysmenorrhea. It was detected that a family history of dysmenorrhea and regular menstrual cycles of the students were dysmenorrhea-affecting factors (P < .05). Seven of 10 students with dysmenorrhea used CAM methods. Heat application of CAM methods for dysmenorrhea management was the most commonly used and also known by the students. The students who experienced severe pain used analgesics (P < .05) and CAM methods (P < .05).

Behavioural processes in social context: female abductions, male herding and female grooming in hamadryas baboons.

PubMed

Polo, Pablo; Colmenares, Fernando

2012-06-01

The formation of bonds between strangers is an event that occurs routinely in many social animals, including humans, and, as social bonds in general, they affect the individuals' welfare and biological fitness. The present study was motivated by an interest in the behavioural processes that drive bond formation in a social context of hostility, in which the incumbent partners vary greatly in physical power and reproductive interests, a situation in which individuals of many group-living species find themselves often throughout their lives. We focused on the quantitative analysis of female abductions via male aggressive herding in a nonhuman primate, the hamadryas baboon, in which intersexual bonds are known to be strong. We tested three hypotheses informed by sexual conflict/sexual coercion theory (male herding-as-conditioning and female grooming-as-appeasement) and by socioecological theory (unit size and female competition). The results supported the predictions: males resorted to coercive tactics (aggressive herding) with abducted females, and abducted females elevated the amount of grooming directed at their new unit males; in fact, they escaped from the otherwise negative effect of unit size on female-to-male grooming. These findings reveal that conflicts of interest are natural ingredients underpinning social bonds and that resorting to coercive aggression may be an option especially when partners differ greatly in their physical power. Copyright © 2012 Elsevier B.V. All rights reserved.

Teaching Students with Autism Spectrum Disorders: Technology, Curriculum, and Common Sense

ERIC Educational Resources Information Center

Ennis-Cole, Demetria

2012-01-01

Autism is a spectrum of disorders which comprises Asperger's Syndrome, Pervasive Developmental Delay-Not Otherwise Specified (PDD-NOS), Rett's Syndrome, Childhood Disintegrative Disorder, and Autistic Disorder. It affects 1 in 110 children (Center for Disease Control and Prevention, [CDC], 2011), and it is a complex neurological disorder that is…

Latent Inhibition Is Affected by Phase of Estrous Cycle in Female Rats

ERIC Educational Resources Information Center

Quinlan, Matthew G.; Duncan, Andrew; Loiselle, Catherine; Graffe, Nicole; Brake, Wayne G.

2010-01-01

Estrogen has been shown to have a strong modulatory influence on several types of cognition in both women and female rodents. Latent inhibition is a task in which pre-exposure to a neutral stimulus, such as a tone, later impedes the association of that stimulus with a particular consequence, such as a shock. Previous work from our lab demonstrates…

Nutritional needs of the female athlete.

PubMed

Manore, M M

1999-07-01

US women, including female athletes, are under ever increasing pressure to be thin ar thinner. this pressure to achieve and maintain a low body weight leads to potentially harmful patterns of long-term dieting or disordered eating, which can affect long-term health. Some of the health consequences of long-term energy restriction in female athletes may include poor energy and nutrient intakes, poor nutritional status, decreased RMR and total daily energy expenditure, increased psychological stress and risk for a clinical eating disorder, and increased risk for exercise-induced amenorrhea and osteoporosis. Female athletes participating in thin-build sports may be at risk for the disorders of the female athlete triad: disordered eating, amenorrhea, and osteoporosis. This triad of disorders can also produce severe health consequences that can influence present and future health. Strategies for helping active women get off the dieting "bandwagon" requires the identification of an appropriate and healthy body weight, good eating and exercise habits, and techniques for maintaining these habits throughout life.

Neonatal amygdala lesions advance pubertal timing in female rhesus macaques

PubMed Central

Stephens, Shannon B.Z.; Raper, Jessica; Bachevalier, Jocelyne; Wallen, Kim

2014-01-01

Summary Social context influences the timing of puberty in both humans and nonhuman primates, such as delayed first ovulation in low-ranking rhesus macaques, but the brain region(s) mediating the effects of social context on pubertal timing are unknown. The amygdala is important for responding to social information and thus, is a potential brain region mediating the effects of social context on pubertal timing. In this study, female rhesus macaques living in large, species-typical, social groups received bilateral neurotoxic amygdala lesions at one month of age and pubertal timing was examined beginning at 14 months of age. Pubertal timing was affected in neonatal amygdala-lesioned females (Neo-A), such that they experienced significantly earlier menarche and first ovulation than did control females (Neo-C). Duration between menarche and first ovulation did not differ between Neo-A and Neo-C females, indicating earlier first ovulation in Neo-A females was likely a consequence of earlier menarche. Social rank of Neo-A females was related to age at menarche, but not first ovulation, and social rank was not related to either event in Neo-C females. It is more likely that amygdalectomy affects pubertal timing through its modulation of GABA-ergic mechanisms rather than as a result of the removal of a social-contextual inhibition on pubertal timing. PMID:25462903

Enhancing the Performance of Female Students in Spoken English

ERIC Educational Resources Information Center

Inegbeboh, Bridget O.

2009-01-01

Female students have been discriminated against right from birth in their various cultures and this affects the way they perform in Spoken English class, and how they rate themselves. They have been conditioned to believe that the male gender is superior to the female gender, so they leave the male students to excel in spoken English, while they…

Dysfunctional error-related processing in female psychopathy

PubMed Central

Steele, Vaughn R.; Edwards, Bethany G.; Bernat, Edward M.; Calhoun, Vince D.; Kiehl, Kent A.

2016-01-01

Neurocognitive studies of psychopathy have predominantly focused on male samples. Studies have shown that female psychopaths exhibit similar affective deficits as their male counterparts, but results are less consistent across cognitive domains including response modulation. As such, there may be potential gender differences in error-related processing in psychopathic personality. Here we investigate response-locked event-related potential (ERP) components [the error-related negativity (ERN/Ne) related to early error-detection processes and the error-related positivity (Pe) involved in later post-error processing] in a sample of incarcerated adult female offenders (n = 121) who performed a response inhibition Go/NoGo task. Psychopathy was assessed using the Hare Psychopathy Checklist-Revised (PCL-R). The ERN/Ne and Pe were analyzed with classic windowed ERP components and principal component analysis (PCA). Consistent with previous research performed in psychopathic males, female psychopaths exhibited specific deficiencies in the neural correlates of post-error processing (as indexed by reduced Pe amplitude) but not in error monitoring (as indexed by intact ERN/Ne amplitude). Specifically, psychopathic traits reflecting interpersonal and affective dysfunction remained significant predictors of both time-domain and PCA measures reflecting reduced Pe mean amplitude. This is the first evidence to suggest that incarcerated female psychopaths exhibit similar dysfunctional post-error processing as male psychopaths. PMID:26060326

The ADRA2B gene in the production of false memories for affective information in healthy female volunteers.

PubMed

Fairfield, Beth; Mammarella, Nicola; Di Domenico, Alberto; D'Aurora, Marco; Stuppia, Liborio; Gatta, Valentina

2017-08-30

False memories are common memory distortions in everyday life and seem to increase with affectively connoted complex information. In line with recent studies showing a significant interaction between the noradrenergic system and emotional memory, we investigated whether healthy volunteer carriers of the deletion variant of the ADRA2B gene that codes for the α2b-adrenergic receptor are more prone to false memories than non-carriers. In this study, we collected genotype data from 212 healthy female volunteers; 91 ADRA2B carriers and 121 non-carriers. To assess gene effects on false memories for affective information, factorial mixed model analysis of variances (ANOVAs) were conducted with genotype as the between-subjects factor and type of memory error as the within-subjects factor. We found that although carriers and non-carriers made comparable numbers of false memory errors, they showed differences in the direction of valence biases, especially for inferential causal errors. Specifically, carriers produced fewer causal false memory errors for scripts with a negative outcome, whereas non-carriers showed a more general emotional effect and made fewer causal errors with both positive and negative outcomes. These findings suggest that putatively higher levels of noradrenaline in deletion carriers may enhance short-term consolidation of negative information and lead to fewer memory distortions when facing negative events. Copyright © 2017 Elsevier B.V. All rights reserved.

Selective preservation of cholinergic MeCP2 rescues specific Rett-syndrome-like phenotypes in MeCP2stop mice.

PubMed

Zhou, Huanhuan; Wu, Wei; Zhang, Ying; He, Haiyang; Yuan, Zhefeng; Zhu, Zhiwei; Zhao, Zhengyan

2017-03-30

RTT is a neurodevelopmental disorder characterized by growth regression, motor dysfunction, stereotypic hand movements, and autism features. Typical Rett syndrome (RTT) is predominantly caused by mutations in X-linked MeCP2 gene which encodes methyl-CpG-binding protein 2 (MeCP2). The brain-abundant MeCP2 protein mainly functions as a transcriptional regulator for neurodevelopment-associated genes. Specific functions of MeCP2 in certain neuron types remain to be known. Although cholinergic system is an important modulating system in brain, how MeCP2 in cholinergic neurons contribute to RTT has not been clearly understood. Here we use a mouse model with selectively activated endogenous MeCP2 in cholinergic neurons in otherwise MeCP2 stop mice to determine the cholinergic MeCP2 effects on rescuing the RTT-like phenotypes. We found cholinergic MeCP2 preservation could reverse some aspects of the RTT-like phenotypes in mice including hypolocomotion and increased anxiety level, and delay the onset of underweight, instead of improving the hypersocial abnormality and the poor general conditions such as short lifespan, low brain weight, and increasing severity score. Our findings suggest that selective activation of cholinergic MeCP2 is sufficient to reverse the locomotor impairment and increased anxiety-like behaviors at least in early symptomatic stage, supporting future development of RTT therapies associated with cholinergic system. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Male sex pheromone components in Heliconius butterflies released by the androconia affect female choice

PubMed Central

Morrison, Colin R.; Salazar, Camilo; Pardo-Diaz, Carolina; Merrill, Richard M.; McMillan, W. Owen; Schulz, Stefan

2017-01-01

Sex-specific pheromones are known to play an important role in butterfly courtship, and may influence both individual reproductive success and reproductive isolation between species. Extensive ecological, behavioural and genetic studies of Heliconius butterflies have made a substantial contribution to our understanding of speciation. Male pheromones, although long suspected to play an important role, have received relatively little attention in this genus. Here, we combine morphological, chemical and behavioural analyses of male pheromones in the Neotropical butterfly Heliconius melpomene. First, we identify putative androconia that are specialized brush-like scales that lie within the shiny grey region of the male hindwing. We then describe putative male sex pheromone compounds, which are largely confined to the androconial region of the hindwing of mature males, but are absent in immature males and females. Finally, behavioural choice experiments reveal that females of H. melpomene, H. erato and H. timareta strongly discriminate against conspecific males which have their androconial region experimentally blocked. As well as demonstrating the importance of chemical signalling for female mate choice in Heliconius butterflies, the results describe structures involved in release of the pheromone and a list of potential male sex pheromone compounds. PMID:29134139

Prevalence and risk factors for female sexual dysfunction among Egyptian women.

PubMed

Ibrahim, Zakia Mahdy; Ahmed, Magdy Refaat; Sayed Ahmed, Waleed Ali

2013-06-01

To assess sexual function among married women and determine associated risk factors for sexual dysfunction. Cross-sectional hospital-based study involving 509 non-pregnant married females 20-59 years old who were enrolled into the study after approval of the ethics committee. The study population was recruited among women attending gynecology outpatient clinic or their relatives visiting inpatients of obstetrics and gynecology department at Suez Canal University Hospital. Female and male partner-related data were collected using an interview questionnaire. Sexual dysfunction was assessed using female sexual function index (FSFI). Mean female age was 39.5 years. About half of the participants were premenopausal (48.7 %). Most of the females were circumcised (71.7 %). Desire and Orgasm domains were the most affected with 52.8 % of the participants having sexual dysfunction. Total FSFI score of ≤26.55 was the cutoff value for diagnosis of FSD and female age, postmenopausal status, duration of marriage, circumcision, partner's age, and the presence of male sexual dysfunction were found to be significant associated factors with FSD. FSD is highly prevalent in Egypt and orgasm and desire scores were the most affected domains. Several personal (female age, postmenopausal status, duration of marriage and circumcision) and male partner (age, and the presence of sexual dysfunction) factors were significantly associated.

Are obstetric outcomes affected by female genital mutilation?

PubMed

Balachandran, Aswini A; Duvalla, Swapna; Sultan, Abdul H; Thakar, Ranee

2018-03-01

Female genital mutilation (FGM) has been associated with adverse obstetric and neonatal outcomes, such as postpartum haemorrhage (PPH), perineal trauma, genital fistulae, obstructed labour and stillbirth. The prevalence of FGM has increased in the UK over the last decade. There are currently no studies available that have explored the obstetric impact of FGM in the UK. The aim of our study was to investigate the obstetric and neonatal outcomes of women with FGM when compared with the general population. We conducted a retrospective case-control study of consecutive pregnant women with FGM over a 5-year period between 1 January 2009 and 31 December 2013. Each woman with FGM was matched for age, ethnicity, parity and gestation with subsequent patients without FGM (control cohort) over the same 5-year period. Outcomes assessed were mode of delivery, duration of labour, estimated blood loss, analgaesia, perineal trauma and foetal outcomes. A total of 242 eligible women (121 FGM, 121 control) were identified for the study. There was a significant increase in the use of episiotomy in the FGM group (p = 0.009) and a significant increase in minor PPH in the control group during caesarean sections (p = 0.0001). There were no differences in all other obstetric and neonatal parameters. In our unit, FGM was not associated with an increased incidence of adverse obstetric and foetal morbidity or mortality.

Age of diagnosis in Rett syndrome: patterns of recognition among diagnosticians and risk factors for late diagnosis

PubMed Central

Tarquinio, Daniel C.; Hou, Wei; Neul, Jeffrey L.; Lane, Jane B.; Barnes, Katherine V.; O’Leary, Heather M.; Bruck, Natalie M.; Kaufmann, Walter E.; Motil, Kathleen J.; Glaze, Daniel G.; Skinner, Steven A.; Annese, Fran; Baggett, Lauren; Barrish, Judy O.; Geerts, Suzanne P.; Percy, Alan K.

2015-01-01

Purpose Diagnosis of Rett syndrome (RTT) is often delayed. We sought to determine type of physician who typically makes the diagnosis of RTT and to identify risk factors for delayed diagnosis. Methods One-thousand eighty-five participants from the multicenter longitudinal RTT natural history study with classic and atypical RTT were recruited from 2006 to 2014. Age of diagnosis, diagnostician, diagnostic criteria, clinical and developmental data were collected. Results Among 919 classic and 166 atypical RTT participants, median diagnosis age was 2.7 years (interquartile range 2.0–4.1) in classic and 3.8 years (interquartile range 2.3–6.9) in atypical RTT. Pediatricians made the diagnosis of classic RTT rarely (5.2%); however, proportion diagnosed by pediatricians increased since 2006. Since the first diagnostic criteria, the age of diagnosis decreased among subspecialists but not pediatricians. Odds of a pediatrician making the diagnosis of classic RTT were higher if a child stopped responding to parental interaction, and lower if they possessed gastro-esophageal reflux, specific stereotypies, lost babbling or the ability to follow commands. Delayed acquisition of basic gross motor skills or finger feeding were associated with younger diagnosis; delayed acquisition of higher level fine motor skills, later onset of supportive features, and normal head circumference were associated with late diagnosis. 33% with microcephaly before 2.5 years were diagnosed after the median age of 2.7 years. Conclusions Age of RTT diagnosis has improved among subspecialists, and pediatricians have made the diagnosis of classic RTT more frequently since 2006. Strategies for educating diagnosticians should incorporate specific risk factors for delayed diagnosis. PMID:25801175

Female circumcision and child mortality in urban Somalia.

PubMed

Mohamud, O A

1991-01-01

In Somalia, a demographer analyzed urban data obtained from the Family Health Survey to examine the effect female circumcision has on child mortality and the mechanism of that effect. Girls undergo female circumcision between 5-12 years old in Somalia. Since sunni circumcision (removal of the clitoral prepuce and tip of the clitoris) and clitoridectomy (removal of the entire clitoris) did not affect child mortality, he used them as the reference group. Infibulation (entire removal of the clitoris and of the labia minora and majora with the remains of the labia majora being sewn together allowing only a small opening for passage of urine) did affect child mortality. Female children who underwent infibulation and whose mothers most likely also underwent infibulation experienced higher mortality (13-72%) than those from other circumcised mothers. Female mortality exceeded male mortality indicating possible son preference. Mothers with clitoridectomy or infibulation had significantly higher infant mortality than those with sunni circumcision with the strongest effects during the neonatal period (95% and 42% higher mortality, respectively; p=.01). The effect of female circumcision on child mortality decreased with increased child's age. This higher than expected mortality among women with clitoridectomy may have been because women with infibulation had more stillbirths which were not counted as births. The exposed vagina of clitoridectomized women is more likely to be infected resulting in high risk of stillbirths and premature births than the closed vagina of infibulated women. The researcher suggested that the policies promoting education and consciousness raising may eventually eradicate female circumcision. This longterm campaign should use mass media, senior women of high status, and respected religious leaders. Legislation prohibiting this practice would only drive it underground under unsanitary conditions. Demographers should no longer ignore female circumcision

Career stress and female managers' health in Taiwan's hospitals: a multilevel model approach.

PubMed

Chen, Duan-Rung; Lin, Yeh-Yun; Chung, Kuo-Piao

2008-01-01

This study investigates how perception-induced stress (barrier) and social capital (facilitator) affect the health of female managers. On the basis of the responses of 229 valid questionnaires of middle- and high-level female managers in large-scale hospitals, using a multilevel data analysis approach, this study investigates how perception-induced stress and social capital influence self-reported poor health of female managers. Analysis results indicate that all 3 perception-induced stresses (i.e., promotion-related procedural justice, promotion rate, and work-family conflict) and 2 social capital variables (i.e., mentor-assisted promotion and higher ranking mentor in other departments) are significantly associated with the health of female mangers. Factors involving the career success of women also affect their health. Health care organizations expecting to benefit from the long-term contribution of female elites must promote organizational equity and more heavily emphasize flexible work schedules, family-friendly policies, and perception management practices. In addition, adequately designed mentorship practices can greatly benefit female managers.

In utero and lactational exposure to low-dose genistein-vinclozolin mixture affects the development and growth factor mRNA expression of the submandibular salivary gland in immature female rats.

PubMed

Kouidhi, Wided; Desmetz, Catherine; Nahdi, Afef; Bergès, Raymond; Cravedi, Jean-Pierre; Auger, Jacques; El May, Michèle; Canivenc-Lavier, Marie Chantal

2012-06-01

It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex-dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor α was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67-positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor α expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures.

Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine-serotonin systems in the prefrontal cortex of juvenile female rats.

PubMed

Castro, Beatriz; Sánchez, Pilar; Torres, Jesús M; Ortega, Esperanza

2015-10-01

Early-life exposure to the endocrine disruptor bisphenol A (BPA) affects brain function and behavior, which might be attributed to its interference with hormonal steroid signaling and/or neurotransmitter systems. Alternatively, the use of structural analogs of BPA, mainly bisphenol F (BPF) and bisphenol S (BPS), has increased recently. However, limited in vivo toxicity data exist. We investigated the effects of BPA, BPF and BPS on 5α-reductase (5α-R), a key enzyme involved in neurosteroidogenesis, as well as on dopamine (DA)- and serotonin (5-HT)-related genes, in the prefrontal cortex (PFC) of juvenile female rats. Gestating Wistar rats were treated with either vehicle or 10 μg/kg/day of BPA, BPF or BPS from gestational day 12 to parturition. Then, female pups were exposed from postnatal day 1 through day 21 (PND21), when they were euthanized and RT-PCR, western blot and quantitative PCR-array experiments were performed. BPA decreased 5α-R2 and 5α-R3 mRNA and protein levels, while both BPF and BPS decreased 5α-R3 mRNA levels in PFC at PND21. Further, BPA, BPF and BPS significantly altered, respectively, the transcription of 25, 56 and 24 genes out of the 84 DA and 5-HT-related genes assayed. Of particular interest was the strong induction by all these bisphenols of Cyp2d4, implicated in corticosteroids synthesis. Our results demonstrate for the first time that BPA, BPF and BPS differentially affect 5α-R and genes related to DA/5-HT systems in the female PFC. In vivo evidence of the potential adverse effects of BPF and BPS in the brain of mammals is provided in this work, raising questions about the safety of these chemicals as substitutes for BPA. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Inhibition of Gsk3b Reduces Nfkb1 Signaling and Rescues Synaptic Activity to Improve the Rett Syndrome Phenotype in Mecp2-Knockout Mice.

PubMed

Jorge-Torres, Olga C; Szczesna, Karolina; Roa, Laura; Casal, Carme; Gonzalez-Somermeyer, Louisa; Soler, Marta; Velasco, Cecilia D; Martínez-San Segundo, Pablo; Petazzi, Paolo; Sáez, Mauricio A; Delgado-Morales, Raúl; Fourcade, Stephane; Pujol, Aurora; Huertas, Dori; Llobet, Artur; Guil, Sonia; Esteller, Manel

2018-05-08

Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG-binding protein 2 gene (MeCP2). We propose here a molecular target involved in RTT: the glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity is deregulated in Mecp2-knockout (KO) mice models, and SB216763, a specific inhibitor, is able to alleviate the clinical symptoms with consequences at the molecular and cellular levels. In vivo, inhibition of Gsk3b prolongs the lifespan of Mecp2-KO mice and reduces motor deficits. At the molecular level, SB216763 rescues dendritic networks and spine density, while inducing changes in the properties of excitatory synapses. Gsk3b inhibition can also decrease the nuclear activity of the Nfkb1 pathway and neuroinflammation. Altogether, our findings indicate that Mecp2 deficiency in the RTT mouse model is partially rescued following treatment with SB216763. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Late adolescent female smoking.

PubMed

Seguire, M; Chalmers, K I

2000-06-01

Although there have been intense efforts to reduce the prevalence of cigarette smoking in the past three decades, smoking continues to be a critical public health problem. An area of particular concern is the increasing number of young women who are smoking. Gender specific research usually does not examine factors affecting smoking behaviours. Information on late adolescent female smoking is not readily found in the literature. The aims of this study were to explore the smoking patterns and processes of late adolescent females and to explore factors which may or may not be helpful in assisting them to stop smoking. A qualitative ethnographic approach was used to uncover the perceptions of 25 adolescent girls of their behaviour. Data were collected using tape-recorded semi-structured interviews and a questionnaire. Items for the questionnaire were derived from the Manitoba Youth Smoking Survey and from the Fagerstrorn Nicotine Tolerance Scale. Qualitative analysis resulted in four stories about smoking: the start story, the smoking story, the quit story, and the looking to the future story. Although many of the findings are congruent with the existing literature, much of the data reflected the purposive nature of smoking in late adolescent girls. Study findings support the need for holistic approaches to health promotion to ameliorate factors affecting smoking behaviour.

"Coffee, tea and me": moderate doses of caffeine affect sexual behavior in female rats.

PubMed

Guarraci, Fay A; Benson, Anastasia

2005-11-01

The present study evaluated the effects of acute caffeine administration on paced mating behavior and partner preference in ovariectomized rats primed with estrogen and progesterone. In Experiment 1, female rats were tested for paced mating behavior following acute administration of caffeine (15 mg/kg). Caffeine shortened the latency to return to a male following an ejaculation. Although this dose of caffeine did not alter the likelihood of leaving a male after receiving sexual stimulation, locomotor activity did increase significantly. Experiment 2 evaluated the dose response characteristics of caffeine (7.5, 15, 30 mg/kg) administration on paced mating behavior. Replicating Experiment 1, caffeine at the lower doses shortened the latency to return to a male following an ejaculation. Finally, to determine whether the effects of caffeine (15 mg/kg) on contact-return latency reflect a change in sexual motivation or merely an inability to inhibit locomotion, rats were tested for partner preference (intact male vs. estrous female) following caffeine administration (Experiment 3). Although caffeine did not disrupt preference for a sexual partner, caffeine selectively increased visits to the male when physical contact was possible. Collectively, these results suggest that the effects of caffeine on female mating behavior may reflect an increase in both sexual motivation and locomotor activity.

Menstrual cycle disorders in female volleyball players.

PubMed

Wodarska, M; Witkoś, J; Drosdzol-Cop, A; Dąbrowska, J; Dąbrowska-Galas, M; Hartman, M; Plinta, R; Skrzypulec-Plinta, V

2013-07-01

The aim of this study was to examine the relation between increased physical activity and menstrual disorders in adolescent female volleyball players. The study was conducted on 210 Polish female volleyball players, aged 13-17 years, the authorship questionnaire was used. The results of the study showed that irregular menstruation occurred in 19% of girls, spotting between menstrual periods in 27% and heavy menstruation was reported in 33% of girls. Out of all volleyball female players participating in the study, 94 girls (45%) declared absence of menstrual periods after regular cycles. Statistical analysis showed that the more training hours per week, the bigger probability of the occurrence of irregular menstruation. It was concluded that the number of hours of volleyball training per week affects regularity of menstrual cycles in female volleyball players. The absence of menstruation might be caused by the duration of training per week or years of training.

Nonvolatile chemical cues affect host-plant ranking by gravid Polygonia c-album females.

PubMed

Mozūraitis, Raimondas; Murtazina, Rushana; Nylin, Sören; Borg-Karlson, Anna-Karin

2012-01-01

In a multiple-choice test, the preference of egg-laying Polygonia c-album (comma butterfly) females was studied for oviposition on plants bearing surrogate leaves treated with crude methanol extracts obtained from leaves of seven host-plant species: Humulus lupulus, Urtica dioica, Ulmus glabra, Salix caprea, Ribes nigrum, Corylus avellana, and Betula pubescens. The ranking order of surrogate leaves treated with host-plant extracts corresponded well to that reported on natural foliage, except R. nigrum. Thus, host-plant choice in P. c-album seems to be highly dependent on chemical cues. Moreover, after two subsequent fractionations using reversed-phase chromatography the nonvolatile chemical cues residing in the most polar water-soluble fractions evidently provided sufficient information for egg-laying females to discriminate and rank between the samples of more and less preferred plants, since the ranking in these assays was similar to that for natural foliage or whole methanol extracts, while the physical traits of the surrogate leaves remained uniform.

Evolution of external female genital mutilation: why do males harm their mates?

PubMed

Mouginot, Pierick; Uhl, Gabriele; Fromhage, Lutz

2017-11-01

Sperm competition may select for male reproductive traits that influence female mating or oviposition rate. These traits may induce fitness costs to the female; however, they may be costly for the males as well as any decrease in female fitness also affects male fitness. Male adaptations to sperm competition manipulate females by altering not only female behaviour or physiology, but also female morphology. In orb-weaving spiders, mating may entail mutilation of external structures of the female genitalia, which prevents genital coupling with subsequent males. Here, we present a game theoretical model showing that external female genital mutilation is favoured even under relatively high costs of mutilation, and that it is favoured by a high number of mate encounters per female and last-male sperm precedence.

Intimate Partner Violence May Be One Mechanism by Which Male Partner Socioeconomic Status and Substance Use Affect Female Partner Health.

PubMed

Assari, Shervin; Jeremiah, Rohan D

2018-01-01

Background: Although male partners' socioeconomic status (SES) and substance use is associated with worse health of female partners, the mechanism behind this link is still unknown. Objectives: To investigate whether intimate partner violence (IPV) is a mechanism by which male partners' SES and substance use influence female partners' self-rated health (SRH) as victims and survivors of IPV. Materials and Methods: Fragile Families and Child Wellbeing Study (FFCWS) is an ongoing population-based cohort. Male and female partners' SES, anxiety, depression, and substance use, and their relationship status were measured at baseline. IPV victimization was also asked among female partners' at baseline. Female partners' subjective health was measured 3 times (baseline-1998, 3 years later-2001, and 5 years later-2003). Using AMOS, we fitted two structural equation models (SEM) for data analysis. In Model 1 we tested direct paths from male partners' SES and mental health to female partners' SRH, in the absence of IPV. In the Model 2 we conceptualized female partners' IPV victimization between male partners' SES and mental health and female partners' SRH. In both models we controlled for the effect of female partners' SES and mental health. Results: In Model 1 , male partners' poor SES and substance use were associated with worse trajectory of SRH of female partner. In Model 2 , male to female IPV was the mechanism by which male partners' SES and substance use were associated with female partners' SRH. Conclusions: IPV is one of the mechanisms by which male partners' SES and substance use can influence female partners' health. That is, IPV may operate as a vehicle by which male partners' social and psychological risk factors impact female partners' health. Thus, this study demonstrates how male partners' socio-ecological risk factors such as low SES and substance use impact female partners' health. Therefore, there is a need for broader socio-ecological approach to IPV

Variations of stereotypies in individuals with Rett syndrome: A nationwide cross-sectional study in Taiwan.

PubMed

Chin Wong, Lee; Hung, Pi-Lien; Jan, Tz-Yun; Lee, Wang-Tso

2017-07-01

Individuals with Rett syndrome (RTT) can have variable manifestations of stereotypies. In this nation-wide cross-sectional study, we recruited all individuals with RTT in Taiwan diagnosed as RTT by neurologists based on genetic findings and diagnostic criteria. The data were collected using questionnaire. A total 43 cases of typical RTT and 15 cases of atypical RTT, aged from 2.1 to 40.1 years, were enrolled. They included 3 (5.2%) in stage II, 42 (72.4%) in stage III, and 13 (22.4%) in stage IV. All individuals presented with at least one stereotypy. Individuals with atypical RTT had more varied stereotypies (mean: 14 ± 6) compared to those with typical RTT (mean: 9 ± 5) (P = 0.003). Flapping (73.3%) and wringing (58.1%) were the most common hand stereotypies in atypical and typical RTT, respectively. Compared with typical RTT, hair pulling, bruxism, retropulsion, and protrusion of lips were more common in atypical RTT (P = 0.003, P = 0.006, P = 0.003 and <0.001, respectively). The number of stereotypies did not differ among different stages, clinical severities, and hand functions. Although there were no age-related changes in stereotypies in atypical RTT, flapping (P = 0.012), clapping (P = 0.044), and mouthing with single hand (P = 0.009) were significantly more prevalent in individuals aged <10 years with typical RTT, and they decreased after 10 years. In conclusion, our study showed that the stereotypical movements varied in typical and atypical RTT, implying the heterogeneous nature of the disease and the pathogenic mechanisms of RTT with atypical features. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1204-1214. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Clarifying the Relation Between Extraversion and Positive Affect.

PubMed

Smillie, Luke D; DeYoung, Colin G; Hall, Phillip J

2015-10-01

This article clarifies two sources of ambiguity surrounding the relation between extraversion and positive affect. First, positive affect is defined differently across major models of the structure of affect. Second, no previous research has examined potentially diverging associations of lower-order aspects of extraversion (i.e., assertiveness and enthusiasm) with positive affect. Australian (Study 1: N = 437, 78% female, Mage  = 20.41) and American (Study 2: N = 262, 39% female, Mage  = 33.86) participants completed multiple measures of extraversion and positive affect. Correlations were employed to examine relations among these measures. In both studies, extraversion was most clearly associated with positive affect as conceptualized within a major factor model of affect-specifically, as positive activation (Watson & Tellegen, 1985)-rather than the valence-based conceptualization of positive affect provided by a circumplex model of affect (Russell, 1980). This was also the case for the assertiveness and enthusiasm aspects of extraversion. Our findings clarify the nature of the positive affective component of extraversion, which is best described in terms of both positive valence and high activation. © 2014 Wiley Periodicals, Inc.

Priming effects for affective vs. neutral faces.

PubMed

Burton, Leslie A; Rabin, Laura; Wyatt, Gwinne; Frohlich, Jonathan; Bernstein Vardy, Susan; Dimitri, Diana

2005-12-01

Affective and Neutral Tasks (faces with negative or neutral content, with different lighting and orientation) requiring reaction time judgments of poser identity were administered to 32 participants. Speed and accuracy were better for the Affective than Neutral Task, consistent with literature suggesting facilitation of performance by affective content. Priming effects were significant for the Affective but not Neutral Task. An Explicit Post-Test indicated no conscious knowledge of the stimulus frequency that was associated with performance facilitation. Faster performance by female vs. male participants, and differential speeds and susceptibility to priming of different emotions were also found. Anger and shock were responded to most rapidly and accurately in several conditions, showed no gender differences, and showed significant priming for both RT and accuracy. Fear and pain were responded to least accurately, were associated with faster female than male reaction time, and the accuracy data showed a kind of reverse priming.

Female genital cutting: confronting cultural challenges and health complications across the lifespan.

PubMed

Farage, Miranda A; Miller, Kenneth W; Tzeghai, Ghebre E; Azuka, Charles E; Sobel, Jack D; Ledger, William J

2015-01-01

Female genital cutting affects over 140 million women worldwide. Prevalent in certain countries of Africa and the Middle East, the practice continues among immigrants to industrialized countries. Female genital cutting is a deeply rooted tradition that confers honor on a woman and her family, yet also a traumatic experience that creates significant dermatological, gynecological, obstetric and infectious disease complications. Little is known about postmenopausal health in cut women. The international community views this practice as a human rights violation. In addition to genital health complications, the medical community must confront an understudied concern of what happens as this population ages. These challenges must be addressed to provide optimal care to women affected by female genital cutting.

iPS cells to model CDKL5-related disorders

PubMed Central

Amenduni, Mariangela; De Filippis, Roberta; Cheung, Aaron Y L; Disciglio, Vittoria; Epistolato, Maria Carmela; Ariani, Francesca; Mari, Francesca; Mencarelli, Maria Antonietta; Hayek, Youssef; Renieri, Alessandra; Ellis, James; Meloni, Ilaria

2011-01-01

Rett syndrome (RTT) is a progressive neurologic disorder representing one of the most common causes of mental retardation in females. To date mutations in three genes have been associated with this condition. Classic RTT is caused by mutations in the MECP2 gene, whereas variants can be due to mutations in either MECP2 or FOXG1 or CDKL5. Mutations in CDKL5 have been identified both in females with the early onset seizure variant of RTT and in males with X-linked epileptic encephalopathy. CDKL5 is a kinase protein highly expressed in neurons, but its exact function inside the cell is unknown. To address this issue we established a human cellular model for CDKL5-related disease using the recently developed technology of induced pluripotent stem cells (iPSCs). iPSCs can be expanded indefinitely and differentiated in vitro into many different cell types, including neurons. These features make them the ideal tool to study disease mechanisms directly on the primarily affected neuronal cells. We derived iPSCs from fibroblasts of one female with p.Q347X and one male with p.T288I mutation, affected by early onset seizure variant and X-linked epileptic encephalopathy, respectively. We demonstrated that female CDKL5-mutated iPSCs maintain X-chromosome inactivation and clones express either the mutant CDKL5 allele or the wild-type allele that serve as an ideal experimental control. Array CGH indicates normal isogenic molecular karyotypes without detection of de novo CNVs in the CDKL5-mutated iPSCs. Furthermore, the iPS cells can be differentiated into neurons and are thus suitable to model disease pathogenesis in vitro. PMID:21750574

iPS cells to model CDKL5-related disorders.

PubMed

Amenduni, Mariangela; De Filippis, Roberta; Cheung, Aaron Y L; Disciglio, Vittoria; Epistolato, Maria Carmela; Ariani, Francesca; Mari, Francesca; Mencarelli, Maria Antonietta; Hayek, Youssef; Renieri, Alessandra; Ellis, James; Meloni, Ilaria

2011-12-01

Rett syndrome (RTT) is a progressive neurologic disorder representing one of the most common causes of mental retardation in females. To date mutations in three genes have been associated with this condition. Classic RTT is caused by mutations in the MECP2 gene, whereas variants can be due to mutations in either MECP2 or FOXG1 or CDKL5. Mutations in CDKL5 have been identified both in females with the early onset seizure variant of RTT and in males with X-linked epileptic encephalopathy. CDKL5 is a kinase protein highly expressed in neurons, but its exact function inside the cell is unknown. To address this issue we established a human cellular model for CDKL5-related disease using the recently developed technology of induced pluripotent stem cells (iPSCs). iPSCs can be expanded indefinitely and differentiated in vitro into many different cell types, including neurons. These features make them the ideal tool to study disease mechanisms directly on the primarily affected neuronal cells. We derived iPSCs from fibroblasts of one female with p.Q347X and one male with p.T288I mutation, affected by early onset seizure variant and X-linked epileptic encephalopathy, respectively. We demonstrated that female CDKL5-mutated iPSCs maintain X-chromosome inactivation and clones express either the mutant CDKL5 allele or the wild-type allele that serve as an ideal experimental control. Array CGH indicates normal isogenic molecular karyotypes without detection of de novo CNVs in the CDKL5-mutated iPSCs. Furthermore, the iPS cells can be differentiated into neurons and are thus suitable to model disease pathogenesis in vitro.

Artificial selection on male genitalia length alters female brain size.

PubMed

Buechel, Séverine D; Booksmythe, Isobel; Kotrschal, Alexander; Jennions, Michael D; Kolm, Niclas

2016-11-30

Male harassment is a classic example of how sexual conflict over mating leads to sex-specific behavioural adaptations. Females often suffer significant costs from males attempting forced copulations, and the sexes can be in an arms race over male coercion. Yet, despite recent recognition that divergent sex-specific interests in reproduction can affect brain evolution, sexual conflict has not been addressed in this context. Here, we investigate whether artificial selection on a correlate of male success at coercion, genital length, affects brain anatomy in males and females. We analysed the brains of eastern mosquitofish (Gambusia holbrooki), which had been artificially selected for long or short gonopodium, thereby mimicking selection arising from differing levels of male harassment. By analogy to how prey species often have relatively larger brains than their predators, we found that female, but not male, brain size was greater following selection for a longer gonopodium. Brain subregion volumes remained unchanged. These results suggest that there is a positive genetic correlation between male gonopodium length and female brain size, which is possibly linked to increased female cognitive ability to avoid male coercion. We propose that sexual conflict is an important factor in the evolution of brain anatomy and cognitive ability. © 2016 The Author(s).

Male cleaner wrasses adjust punishment of female partners according to the stakes

PubMed Central

Raihani, Nichola J.; Pinto, Ana I.; Grutter, Alexandra S.; Wismer, Sharon; Bshary, Redouan

2012-01-01

Punishment is an important deterrent against cheating in cooperative interactions. In humans, the severity of cheating affects the strength of punishment which, in turn, affects the punished individual's future behaviour. Here, we show such flexible adjustments for the first time in a non-human species, the cleaner wrasse (Labroides dimidiatus), where males are known to punish female partners. We exposed pairs of cleaners to a model client offering two types of food, preferred ‘prawn’ items and less-preferred ‘flake’ items. Analogous to interactions with real clients, eating a preferred prawn item (‘cheating’) led to model client removal. We varied the extent to which female cheating caused pay-off reduction to the male and measured the corresponding severity of male punishment. Males punished females more severely when females cheated during interactions with high value, rather than low value, model clients; and when females were similar in size to the male. This pattern may arise because, in this protogynous hermaphrodite, cheating by similar-sized females may reduce size differences to the extent that females change sex and become reproductive competitors. In response to more severe punishment from males, females behaved more cooperatively. Our results show that punishment can be adjusted to circumstances and that such subtleties can have an important bearing on the outcome of cooperative interactions. PMID:21676980

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

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.

Frequency-dependent pollinator discrimination acts against female plants in the gynodioecious Geranium maculatum.

PubMed

Van Etten, Megan L; Chang, Shu-Mei

2014-12-01

Gynodioecy, the co-occurrence of female and hermaphroditic individuals, is thought to be an intermediate step between hermaphroditism and separate sexes, a major transition in flowering plants. Because retaining females in a population requires that they have increased seed fitness (to compensate for the lack of pollen fitness), factors that affect seed fitness are of great importance to the evolution of this mating system and have often been studied. However, factors negatively affecting female fitness are equally important and have been largely neglected. One such factor stems from female flowers being less attractive to insects than hermaphrodite flowers, thereby decreasing their relative fitness. To test the severity and consequences of this type of pollinator discrimination in Geranium maculatum, experimental populations with the range of sex ratios observed in nature were created, ranging from 13 % to 42 % females. Pollinators were observed in order to measure the strength of discrimination, and pollen deposition and seed production of both sexes were measured to determine the fitness consequences of this discrimination. Additionally a comparison was made across the sex ratios to determine whether discrimination was frequency-dependent. It was found that female flowers, on average, were visited at half of the rate of hermaphrodite flowers, which decreased their pollen receipt and seed production. Additionally, females were most discriminated against when rare, due to both changes in the pollinators' behaviour and a shift in pollinator composition. The results suggest that pollinator discrimination negatively affects females' relative fitness when they are rare. Thus, the initial spread of females in a population, the first step in the evolution of gynodioecy, may be made more difficult due to pollinator discrimination. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions

Female genital mutilation: a urology focus.

PubMed

Clarke, Elinor

2016-10-13

Female genital mutilation (FGM) is a collective term for the deliberate alteration, removal and cutting of the female genitalia. It has no known health benefits and can have negative physical and psychological consequences. The number of women and girls in the UK that are affected by FGM is unknown. Recent NHS data suggested that FGM has been evident (declared or observed) in women who have accessed health care; however, there are gaps in knowledge and a limited evidence base on the health consequences of FGM. This article explores the urological complications experienced by women who have undergone this practice, and the effects this can have on their health and wellbeing.

Factors affecting the retention of first-year female science and engineering students at the University of Michigan

NASA Astrophysics Data System (ADS)

Ballard, Juliet Webb

Alarming to many academics is that while the numbers of female students (at the University of Michigan in particular) in SEM (Science, Engineering, and Mathematics) departments have shown increases in enrollment over the past decades, the number of female professionals in the field has decreased. The purpose of the study was to determine the environmental perceptions of female SEM students in the Women in Science and Engineering (WISE) Program at the University of Michigan. The WISE-RP (Residence Program) is an existing living and learning education program at the university that was designed to facilitate the successful retention and graduation of undergraduate female SEM students in the capacity that the admissions statistics should logically imply. The objectives of the study included identification of the perceptions of female students that contribute to, and foster retention of students participating in the WISE-RP program. The knowledge obtained from this evaluation will guide the University of Michigan in formulating specific interventions and retention approaches, both in and out of the classroom. This was achieved by identifying (among other things) commonality of experiences, and female student's perceptions of acceptance, integration and interactivity. The data used in this secondary analysis was collected over a 2 year period (1999--2001). The primary instrument used for data collection was a structured interview protocol utilizing focus groups. The population and samples studied were comprised of: a research project consisting of 36 focus groups from WISE-RP, University Research Opportunity Program, and the University Research Opportunity in Residence Programs; the sample size of the initial project was 180 first year SEM male and female students. The research project consisted of working with a senior research team at the University of Michigan to develop a structured interview instrument, pilot the instrument, and select focus groups. Content

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

What’s in a Face? How Face Gender and Current Affect Influence Perceived Emotion

PubMed Central

Harris, Daniel A.; Hayes-Skelton, Sarah A.; Ciaramitaro, Vivian M.

2016-01-01

Faces drive our social interactions. A vast literature suggests an interaction between gender and emotional face perception, with studies using different methodologies demonstrating that the gender of a face can affect how emotions are processed. However, how different is our perception of affective male and female faces? Furthermore, how does our current affective state when viewing faces influence our perceptual biases? We presented participants with a series of faces morphed along an emotional continuum from happy to angry. Participants judged each face morph as either happy or angry. We determined each participant’s unique emotional ‘neutral’ point, defined as the face morph judged to be perceived equally happy and angry, separately for male and female faces. We also assessed how current state affect influenced these perceptual neutral points. Our results indicate that, for both male and female participants, the emotional neutral point for male faces is perceptually biased to be happier than for female faces. This bias suggests that more happiness is required to perceive a male face as emotionally neutral, i.e., we are biased to perceive a male face as more negative. Interestingly, we also find that perceptual biases in perceiving female faces are correlated with current mood, such that positive state affect correlates with perceiving female faces as happier, while we find no significant correlation between negative state affect and the perception of facial emotion. Furthermore, we find reaction time biases, with slower responses for angry male faces compared to angry female faces. PMID:27733839

Severe and moderate haemophilia A and B in US females.

PubMed

Di Michele, D M; Gibb, C; Lefkowitz, J M; Ni, Q; Gerber, L M; Ganguly, A

2014-03-01

Haemophilia A and B are rare X-lined hemorrhagic disorders that typically affect men. Women are usually asymptomatic carriers, but may be symptomatic and, rarely, also express severe (factor VIII (FVIII) or factor IX (FIX) <0.01 U mL(-1)) or moderately severe (FVIII/FIX 0.01-0.05 U mL(-1)) phenotypes. However, data on clinical manifestations, genotype and the psychosocial ramifications of illness in severely affected females remain anecdotal. A national multi-centre retrospective study was conducted to collect a comprehensive data set on affected US girls and women, and to compare clinical observations to previously published information on haemophilic males of comparable severity and mildly affected haemophilic females. Twenty-two severe/moderate haemophilia A/B subjects were characterized with respect to clinical manifestations and disease complications; genetic determinants of phenotypic severity; and health-related quality of life (HR-QoL). Clinical data were compared as previously indicated. Female patients were older than male patients at diagnosis, but similarly experienced joint haemorrhage, disease- and treatment-related complications and access to treatment. Gynaecological and obstetrical bleeding was unexpectedly infrequent. F8 or F9 mutations, accompanied by extremely skewed X-chromosome inactivation pattern (XIP), were primary determinants of severity. HR-QoL was diminished by arthropathy and viral infection. Using systematic case verification of participants in a national surveillance registry, this study elucidated the genetics, clinical phenotype and quality of life issues in female patients with severe/moderate haemophilia. An ongoing international case-controlled study will further evaluate these observations. Novel mechanistic questions are raised about the relationship between XIP and both age and tissue-specific FVIII and FIX expression. © 2014 John Wiley & Sons Ltd.

Evolution of external female genital mutilation: why do males harm their mates?

PubMed Central

Uhl, Gabriele

2017-01-01

Sperm competition may select for male reproductive traits that influence female mating or oviposition rate. These traits may induce fitness costs to the female; however, they may be costly for the males as well as any decrease in female fitness also affects male fitness. Male adaptations to sperm competition manipulate females by altering not only female behaviour or physiology, but also female morphology. In orb-weaving spiders, mating may entail mutilation of external structures of the female genitalia, which prevents genital coupling with subsequent males. Here, we present a game theoretical model showing that external female genital mutilation is favoured even under relatively high costs of mutilation, and that it is favoured by a high number of mate encounters per female and last-male sperm precedence. PMID:29291104

Epileptic encephalopathy in a girl with an interstitial deletion of Xp22 comprising promoter and exon 1 of the CDKL5 gene.

PubMed

Bahi-Buisson, Nadia; Girard, Benoit; Gautier, Agnes; Nectoux, Juliette; Fichou, Yann; Saillour, Yoann; Poirier, Karine; Chelly, Jamel; Bienvenu, Thierry

2010-01-05

We report a 2-year-old girl with early onset seizures variant of Rett syndrome with a deletion at Xp22 detected by multiplex ligation-dependent probe amplification (MLPA) technique. This patient presented with tonic seizures at 7 days of life. Subsequently, she developed infantile spasms at three months and finally refractory myoclonic epilepsy. She demonstrated severe encephalopathy with hypotonia, deceleration of head growth, with eye gaze but limited eye pursuit, no language, limited hand use, and intermittent hand stereotypies. This combination of clinical features, suggestive of early onset variant of Rett syndrome led us to screen the CDKL5 gene. In a first step, screening of the whole coding sequence of the CDKL5 gene revealed no point mutations. In a second step, we searched gross rearrangements by MLPA and identified a microdeletion affecting both the promoter and exon 1 in CDKL5. Subsequent analysis on a Nimblegen HD2 microarray confirmed a deletion of approximately 300 kb at Xp22, including the BEND2, SCML2, and CDKL5 genes. In conclusion, our report suggests that searching for large rearrangements in CDKL5 should be considered in girls with early onset seizures and Rett-like features. (c) 2009 Wiley-Liss, Inc.

A structural comparison of female-male and female-female mounting in Japanese macaques (Macaca fuscata).

PubMed

Ottenheimer Carrier, Lydia; Leca, Jean-Baptiste; Pellis, Sergio; Vasey, Paul L

2015-10-01

In certain populations, female Japanese macaques (Macaca fuscata) mount both males and females. Vasey (2007) proposed that female-female sexual mounting in Japanese macaques may be a neutral evolutionary by-product of a purported adaptation, namely, female-male mounting. In this study, we aim to further examine the proposed link between female-male and female-female mounting in Japanese macaques by comparing the structural characteristics that define both forms of mounting. We do so using Eshkol-Wachman Movement Notation (EWMN), a globographic reference system that can be used to describe the position of body segments. No significant differences were observed in the female mounters' positioning of eight different body segments (i.e., lower torso, mid-torso, upper torso, upper arm, lower arm, upper leg, lower leg, and foot) during female-male and female-female mounting. This finding lends support to the conclusion that female-female and female-male mounting are structurally, and thus, evolutionarily, related. Copyright © 2015 Elsevier B.V. All rights reserved.

Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats

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

Trabace, L., E-mail: trabace@unifg.it; Zotti, M.; Morgese, M.G.

2011-09-01

Carvacrol is the major constituent of essential oils from aromatic plants. It showed antimicrobial, anticancer and antioxidant properties. Although it was approved for food use and included in the chemical flavorings list, no indication on its safety has been estimated. Since the use of plant extracts is relatively high among women, aim of this study was to evaluate carvacrol effects on female physiology and endocrine profiles by using female rats in proestrus and diestrus phases. Serotonin and metabolite tissue content in prefrontal cortex and nucleus accumbens, after carvacrol administration (0.15 and 0.45 g/kg p.o.), was measured. Drug effects in behavioralmore » tests for alterations in motor activity, depression, anxiety-related behaviors and endocrine alterations were also investigated. While in proestrus carvacrol reduced serotonin and metabolite levels in both brain areas, no effects were observed in diestrus phase. Only in proestrus phase, carvacrol induced a depressive-like behavior in forced swimming test, without accompanying changes in ambulation. The improvement of performance in FST after subchronic treatment with fluoxetine (20 mg/kg) suggested a specific involvement of serotonergic system. No differences were found across the groups with regard to self-grooming behavior. Moreover, in proestrus phase, carvacrol reduced only estradiol levels without binding hypothalamic estradiol receptors. Our study showed an estrous-stage specific effect of carvacrol on depressive behaviors and endocrine parameters, involving serotonergic system. Given the wide carvacrol use not only as feed additive, but also as cosmetic essence and herbal remedy, our results suggest that an accurate investigation on the effects of its chronic exposure is warranted. - Highlights: > Carvacrol induced a depressive-like phenotype in rats, depending on ovarian cyclicity. > Carvacrol selectively reduced serotonin content in female rats in proestrus phase. > Carvacrol reduced

Committee Opinion No.702: Female Athlete Triad.

PubMed

2017-06-01

The female athlete triad is a medical condition observed in physically active females involving three components: 1) low energy availability with or without disordered eating, 2) menstrual dysfunction, and 3) low bone density. An individual does not need to show clinical manifestations of all three components of the female athlete triad simultaneously to be affected by the condition. Consequences of these clinical conditions may not be completely reversible, so prevention, early diagnosis, and intervention are critical. All athletes are at risk of the female athlete triad, regardless of body build or sport. All active females should be assessed for components of the triad and further evaluation should be performed if one or more components are identified. The obstetrician-gynecologist has the opportunity to screen athletes for components of the female athlete triad at comprehensive visits for preventive care. Using the menstrual cycle as a vital sign is a useful tool for identifying athletes at risk of female athlete triad and should be an integral part of the preparticipatory sports physical. The goal of treatment for those diagnosed with female athlete triad is restoration of regular menses as a clinical marker of reestablishment of energy balance and enhancement of bone mineral density. The female athlete triad is a result of energy imbalance; thus, adjusting the energy expenditure and energy availability is the main intervention. Pharmacologic treat-ment may be considered when nonpharmacologic treatment has failed. A team approach involving the patient, obstetrician-gynecologist, sports nutritionist, coaches, parents, and mental health care provider, if indicated, is optimal.

Physical Education and Female Participation: A Case Study of Teachers' Perspectives and Strategies

ERIC Educational Resources Information Center

Murphy, Brooke; Dionigi, Rylee A.; Litchfield, Chelsea

2014-01-01

We argue that gender issues in physical education (PE) remain in some schools, despite advances in PE research and curricula aimed at engaging females in PE. We interviewed five Australian PE teachers (1 male and 4 females) at a co-educational, regional high school about the factors affecting female participation in PE and the strategies they used…

Affective changes during the postpartum period: Influences of genetic and experiential factors.

PubMed

Agrati, Daniella; Lonstein, Joseph S

2016-01-01

This article is part of a Special Issue "Parental Care". The postpartum period involves some truly transformational changes in females' socioemotional behaviors. For most female laboratory rodents and women, these changes include an improvement in their affective state, which has positive consequences for their ability to sensitively care for their offspring. There is heterogeneity among females in the likelihood of this positive affective change, though, and some women experience elevated anxiety or depression (or in rodents anxiety- or depression-related behaviors) after giving birth. We aim to contribute to the understanding of this heterogeneity in maternal affectivity by reviewing selected components of the scientific literatures on laboratory rodents and humans examining how mothers' physical contact with her infants, genetics, history of anxiety and depression and early-life and recent-life experiences contribute to individual differences in postpartum affective states. These studies together indicate that multiple biological and environmental factors beyond female maternal state shape affective responses during the postpartum period, and probably do so in an interactive manner. Furthermore, the similar capacity of some of these factors to modulate anxiety and depression in human and rodent mothers suggests cross-species conservation of mechanisms regulating postpartum affectivity. Copyright © 2015 Elsevier Inc. All rights reserved.

Intrasexual competition in females: evidence for sexual selection?

PubMed

Rosvall, Kimberly A

2011-11-01

In spite of recent interest in sexual selection in females, debate exists over whether traits that influence female-female competition are sexually selected. This review uses female-female aggressive behavior as a model behavioral trait for understanding the evolutionary mechanisms promoting intrasexual competition, focusing especially on sexual selection. I employ a broad definition of sexual selection, whereby traits that influence competition for mates are sexually selected, whereas those that directly influence fecundity or offspring survival are naturally selected. Drawing examples from across animal taxa, including humans, I examine 4 predictions about female intrasexual competition based on the abundance of resources, the availability of males, and the direct or indirect benefits those males provide. These patterns reveal a key sex difference in sexual selection: Although females may compete for the number of mates, they appear to compete more so for access to high-quality mates that provide direct and indirect (genetic) benefits. As is the case in males, intrasexual selection in females also includes competition for essential resources required for access to mates. If mate quality affects the magnitude of mating success, then restricting sexual selection to competition for quantity of mates may ignore important components of fitness in females and underestimate the role of sexual selection in shaping female phenotype. In the future, understanding sex differences in sexual selection will require further exploration of the extent of mutual intrasexual competition and the incorporation of quality of mating success into the study of sexual selection in both sexes.

Factors influencing fluoxetine-induced sexual dysfunction in female rats

PubMed Central

Adams, Sarah; Heckard, Danyeal; Hassell, James; Uphouse, Lynda

2012-01-01

Treatment with selective serotonin reuptake inhibitors, such as fluoxetine, produces sexual side effects with low sexual desire being the most prevalent effect in females. In few studies have preclinical models for such antidepressant-induced sexual dysfunction been fruitful. In the current manuscript, the effects of fluoxetine on multiple measures of female sexual motivation and sexual receptivity were examined. Ovariectomized, Fischer rats were primed with 10 μg estradiol benzoate and 500 μg progesterone. Partner preference, active investigation of the male, and measures of sexual behavior were examined after injection with 15 mg/kg fluoxetine. Factors (pretesting for sexual behavior, size of the test arena, non-contact time with a male) that differ among experiments designed to study antidepressant-induced female rat sexual dysfunction were studied. The male preference ratio was not affected by fluoxetine treatment but active investigation of the male was reduced; lordosis behavior was inhibited and pretesting for sexual receptivity amplified fluoxetine's inhibition; size of the testing arena or non-contact experience with the male had no effect. Regardless of test condition, when given the opportunity to escape from the male, fluoxetine-treated females displayed escape behavior. Measures of male preference and active investigation, but not lordosis behavior, appeared to be affected by fluoxetine's impact on activity. The collective data provided a behavioral profile of fluoxetine-induced sexual dysfunction. These findings reinforce the value of multiple measures when attempting to model antidepressant-induced female sexual dysfunction. PMID:22835821

Sexual selection favours male parental care, when females can choose

PubMed Central

Alonzo, Suzanne H.

2012-01-01

Explaining the evolution of male care has proved difficult. Recent theory predicts that female promiscuity and sexual selection on males inherently disfavour male care. In sharp contrast to these expectations, male-only care is often found in species with high extra-pair paternity and striking variation in mating success, where current theory predicts female-only care. Using a model that examines the coevolution of male care, female care and female choice; I show that inter-sexual selection can drive the evolution of male care when females are able to bias mating or paternity towards parental males. Surprisingly, female choice for parental males allows male care to evolve despite low relatedness between the male and the offspring in his care. These results imply that predicting how sexual selection affects parental care evolution will require further understanding of why females, in many species, either do not prefer or cannot favour males that provide care. PMID:22171082

Female remating, sperm competition and sexual selection in Drosophila.

PubMed

Singh, Shree Ram; Singh, Bashisth N; Hoenigsberg, Hugo F

2002-09-30

Female remating is fundamental to evolutionary biology as it determines the pattern of sexual selection and sexual conflict. Remating in females is an important component of Drosophila mating systems because it affects sperm usage patterns and sexual selection. Remating is common in females of many species of Drosophila in both natural and laboratory populations. It has been reported in many insect species and also in vertebrates. Female remating is a prerequisite for sperm competition between males, and the consequences of this competition, such as sperm precedence or sperm displacement, have been reported for many species of Drosophila. Female remating is dependent on the amount of sperm stored, the male seminal fluid components, nutrition, the quantity of eggs laid, experimental design and density of flies in laboratory. Remating by a female is an insurance against male sterility and sub-fertility and increases genetic heterogeneity of female offspring. Remating gives greater female productivity in many species of Drosophila. We examined female remating with respect to sperm competition and sexual selection in Drosophila and addressed the possible benefits for females. We also reviewed the role of accessory gland fluid in remating, costs associated with remating, the genetic basis of female remating and some possible mechanisms of sperm competition in the light of last male sperm priority and paternity assurance in Drosophila and other insects. We also suggest future areas of research.

How much better are females? The occurrence of female advantage, its proximal causes and its variation within and among gynodioecious species

PubMed Central

Dufay, Mathilde; Billard, Emmanuelle

2012-01-01

Background Gynodioecy is a reproductive system of interest for evolutionary biologists, as it poses the question of how females can be maintained while competing with hermaphrodites that possess both male and female functions. One necessary condition for the maintenance of this polymorphism is the occurrence of a female advantage, i.e. a better seed production or quality by females compared with hermaphrodites. Theoretically, its magnitude can be low when sterility mutations are cytoplasmic, while a 2-fold advantage is needed in the case of nuclear sterility. Such a difference is often thought to be due to reduced inbreeding depression in obligatory outcrossed females. Finally, variation in sex ratio and female advantage occur among populations of some gynodioecious species, though the prevalence of such variation is unknown. Scope By reviewing and analysing the data published on 48 gynodioecious species, we examined three important issues about female advantage. (1) Are reduced selfing and inbreeding depression likely to be the major cause of female advantage? (2) What is the magnitude of female advantage and does it fit theoretical predictions? (3) Does the occurrence or the magnitude of female advantage vary among populations within species and why? Conclusions It was found that a female advantage occurred in 40 species, with a magnitude comprised between 1 and 2 in the majority of cases. In many species, reduced selfing may not be a necessary cause of this advantage. Finally, female advantage varied among populations in some species, but both positive and negative correlations were found with female frequency. The role of reduced selfing in females for the evolution of gynodioecy, as well as the various processes that affect sex ratios and female advantage in populations are discussed. PMID:21459860

Chemosignalling effects of human tears revisited: Does exposure to female tears decrease males' perception of female sexual attractiveness?

PubMed

Gračanin, Asmir; van Assen, Marcel A L M; Omrčen, Višnja; Koraj, Ivana; Vingerhoets, Ad J J M

2017-01-01

Gelstein et al. reported the results of three experiments suggesting a dampening influence of inhalation of female emotional tears on males' arousal and perception of female sexual attractiveness, specifically in non-sexual situations. This prompted the hypothesis that crying exerts its influence on others not only via the auditory and visual mode but also via chemosignals. In three studies, we attempted to replicate and extend Gelstein et al.'s findings by including an additional condition with irritant tears, by using pictures of sexually attractive women, and by testing related hypotheses on the pro-social effects of exposure to tears. All three studies, separately or combined in a meta-analysis, failed to replicate the original inhibitory effects of tears. In addition, sniffing tears did not affect measures of connectedness, aggression and pro-social behaviour. It is concluded that the effects of female tears on male arousal and perception of female sexual attractiveness, if any, are very weak at best. Rather, it seems that crying exerts its strong inter-personal effects through the visual and auditory sensory channels.

Emotional Intelligence in Incarcerated Female Offenders With Psychopathic Traits.

PubMed

Edwards, Bethany G; Ermer, Elsa; Salovey, Peter; Kiehl, Kent A

2018-03-05

Emotional impairment is a core feature of psychopathy, and the disorder has been linked to an inability to recognize and regulate emotion, leading to deficiencies in empathy and difficulties in social functioning. This study investigated associations among psychopathic traits and ability-based emotional intelligence (EI) in female offenders and integrated data with previously published male offender data (Ermer, Kahn, Salovey, & Kiehl, 2012) to examine gender differences in relationships. Results showed that female offenders were impaired in the understanding and management of emotion relative to the general population, and that female offenders scored higher than male offenders in EI. Affective psychopathic traits (e.g., callousness) yielded a small relationship with difficulties in managing emotion in female offenders, and few gender differences in relationships between psychopathy and EI were found. Findings contribute to literature on emotional functioning in females with psychopathic traits and further understanding of gender differences in emotional abilities among offenders.

Does negative affect mediate the relationship between daily PTSD symptoms and daily alcohol involvement in female rape victims? Evidence from 14 days of interactive voice response assessment

PubMed Central

Cohn, Amy; Hagman, Brett T.; Moore, Kathleen; Mitchell, Jessica; Ehlke, Sarah

2014-01-01

The negative reinforcement model of addiction posits that individuals may use alcohol to reduce with negative affective (NA) distress. The current study investigated the mediating effect of daily NA on the relationship between daily PTSD symptoms and same-day and next-day alcohol involvement (consumption and desire to drink) in a sample of 54 non-treatment-seeking female rape victims who completed 14 days of interactive voice response assessment. The moderating effect of lifetime alcohol use disorder diagnosis (AUD) on daily relationships was also examined. Multilevel models suggested that NA mediated the relationship between PTSD and same-day, but not next-day alcohol involvement. NA was greater on days characterized by more severe PTSD symptoms, and alcohol consumption and desire to drink were greater on days characterized by higher NA. Further, daily PTSD symptoms and NA were more strongly associated with same-day (but not next-day) alcohol consumption and desire to drink for women with an AUD than without. Results suggest that NA plays an important role in female rape victims’ daily alcohol use. Differences between women with and without an AUD indicate the need for treatment matching to sub-types of female rape victims. PMID:24731112

The effect of intrauterine position on the survival, reproduction and home range size of female house mice (Mus musculus)

Treesearch

W. J. Zielinski; F. S. vom Saal; J. G. Vandenbergh

1992-01-01

In laboratory studies using albino house mice, a female's prior intrauterine position can affect many postnatal physiological, morphological and behavioral characteristics. Females flanked by males in utero (2M females) exhibit more aggressive dominance than females flanked by females (OM females). Thus, wild 2M...

Effects of early-life exposure to THIP on brainstem neuronal excitability in the Mecp2-null mouse model of Rett syndrome before and after drug withdrawal.

PubMed

Zhong, Weiwei; Johnson, Christopher M; Cui, Ningren; Oginsky, Max F; Wu, Yang; Jiang, Chun

2017-01-01

Rett syndrome (RTT) is mostly caused by mutations of the X-linked MECP2 gene. Although the causal neuronal mechanisms are still unclear, accumulating experimental evidence obtained from Mecp2 -/Y mice suggests that imbalanced excitation/inhibition in central neurons plays a major role. Several approaches may help to rebalance the excitation/inhibition, including agonists of GABA A receptors (GABA A R). Indeed, our previous studies have shown that early-life exposure of Mecp2-null mice to the extrasynaptic GABA A R agonist THIP alleviates several RTT-like symptoms including breathing disorders, motor dysfunction, social behaviors, and lifespan. However, how the chronic THIP affects the Mecp2 -/Y mice at the cellular level remains elusive. Here, we show that the THIP exposure in early lives markedly alleviated hyperexcitability of two types of brainstem neurons in Mecp2 -/Y mice. In neurons of the locus coeruleus (LC), known to be involved in breathing regulation, the hyperexcitability showed clear age-dependence, which was associated with age-dependent deterioration of the RTT-like breathing irregularities. Both the neuronal hyperexcitability and the breathing disorders were relieved with early THIP treatment. In neurons of the mesencephalic trigeminal nucleus (Me5), both the neuronal hyperexcitability and the changes in intrinsic membrane properties were alleviated with the THIP treatment in Mecp2-null mice. The effects of THIP on both LC and Me5 neuronal excitability remained 1 week after withdrawal. Persistent alleviation of breathing abnormalities in Mecp2 -/Y mice was also observed a week after THIP withdrawal. These results suggest that early-life exposure to THIP, a potential therapeutic medicine, appears capable of controlling neuronal hyperexcitability in Mecp2 -/Y mice, which occurs in the absence of THIP in the recording solution, lasts at least 1 week after withdrawal, and may contribute to the RTT-like symptom mitigation. © 2017 The Authors

What Affects Reintegration of Female Drug Users after Prison Release? Results of a European Follow-Up Study

ERIC Educational Resources Information Center

Zurhold, Heike; Moskalewicz, Jacek; Sanclemente, Cristina; Schmied, Gabriele; Shewan, David; Verthein, Uwe

2011-01-01

The main objective of this follow-up study is to explore factors influencing the success or failure of women in reintegrating after their release from prison. Female drug users in five European cities were tracked after being released from prison. Out of 234 female prisoners contacted in prisons, 59 were included in the follow-up study. Structured…

[Does self-esteem affect body dissatisfaction levels in female adolescents?].

PubMed

Fortes, Leonardo de Sousa; Cipriani, Flávia Marcele; Coelho, Fernanda Dias; Paes, Santiago Tavares; Ferreira, Maria Elisa Caputo

2014-09-01

To evaluate the influence of self-esteem on levels of body dissatisfaction among adolescent females. A group of 397 adolescents aged 12 to 17 years were enrolled in the study. The Body Shape Questionnaire (BSQ) was applied to assess body dissatisfaction. The Rosenberg Self-Esteem Scale was used to assess self-esteem. Weight, height, and skinfold thickness were also measured. These anthropometric data were controlled in the statistical analyses. The multiple regression model indicated influence of "positive self-esteem" (R(2)=0.16; p=0.001) and "negative self-esteem" (R(2)=0.23; p=0.001) subscales on the BSQ scores. Univariate analysis of covariance demonstrated differences in BSQ scores (p=0.001) according to groups of self-esteem. It was concluded that self-esteem influenced body dissatisfaction in adolescent girls from Juiz de Fora, MG. Copyright © 2014 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Hostile sexist male patients and female doctors: a challenging encounter.

PubMed

Klöckner Cronauer, Christina; Schmid Mast, Marianne

2014-01-01

Patient characteristics and attitudes can affect how patients react to the physician's communication style, and this reaction can then influence consultation outcomes. The goal of the present study was to investigate whether the attitude of a sexist male patient affects how he perceives a female physician's nonverbal communication and whether this then results in expecting less positive consultation outcomes. Participants were analog patients who viewed four videotaped male and four videotaped female physicians in a consultation with one of their patients. Physician videos were preselected to represent a range of high and low patient-centered physician nonverbal behavior. Participants filled in questionnaires to assess how patient-centered they perceived the female and male physicians' nonverbal communication to be, and participants indicated how positive they expected the consultation outcomes to be. Moreover, we assessed the participants' sexist attitudes with a questionnaire measuring hostile and benevolent sexism. Students (N = 60) from a French-speaking university in Switzerland were recruited on campus. The main outcome measures were the extent to which analog patients expect the consultation outcomes to be positive (high satisfaction, increased trust in the physician, intention to adhere to treatment recommendations, and perceived physician competence) and the extent to which analog patients perceive physicians as patient-centered (judged from the physicians' nonverbal cues). Male analog patients' hostile sexism was negatively related to perceiving the physicians as patient-centered, and male analog patients' hostile sexism was also negatively related to expected positive consultation outcomes. For male patients viewing female physicians, mediation analysis revealed that perceived physician patient-centeredness mediated the negative relationship between hostile sexism and expected positive consultation outcomes. Male hostile sexist patients perceive a female

A novel mutation in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene associated with a severe Rett phenotype.

PubMed

Sprovieri, T; Conforti, F L; Fiumara, A; Mazzei, R; Ungaro, C; Citrigno, L; Muglia, M; Arena, A; Quattrone, A

2009-02-15

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have recently been reported in patients with severe neurodevelopmental disorder characterized by early-onset seizures, infantile spasms, severe psychomotor impairment and very recently, in patients with Rett syndrome (RTT)-like phenotype. Although the involvement of CDKL5 in specific biological pathways and its neurodevelopmental role have not been completely elucidated, the CDKL5 appears to be physiologically related to the MECP2 gene. Here we report on the clinical and CDKL5 molecular investigation in a very unusual RTT case, with severe, early-neurological involvement in which we have shown in a previous report, a novel P388S MECP2 mutation [Conforti et al. (2003); Am J Med Genet A 117A: 184-187]. The patient has had severe psychomotor delay since the first month of life and infantile spasms since age 5 months. Moreover, at age 5 years the patient suddenly presented with renal failure. The severe pattern of symptoms in our patient, similar to a CDKL5 phenotype, prompted us to perform an analysis of the CDKL5, which revealed a novel missense mutation never previously described. The X-inactivation assay was non-informative. In conclusion, this report reinforces the observation that the CDKL5 phenotype overlaps with RTT and that CDKL5 analysis is recommended in patients with a seizure disorder commencing during the first months of life.

Poverty as a contextual factor affecting sexual health behavior among female sex workers in India.

PubMed

Dasgupta, Satarupa

2013-06-01

A thorough understanding of the environmental and structural factors that precipitate unsafe sexual practices is necessary for HIV/AIDS-prevention research among high-risk population groups like commercial sex workers. I examined how poverty contextualizes sexual health behavior, including condom compliance among commercial female sex workers in a red light district in Calcutta, India. For my research I did an ethnographic study and conducted in-depth interviews of 37 commercial female sex workers. I found that poverty, instead of serving as a catalyst for poor health choices among sex workers, acted as an impetus for pursuing safe sex practices and remaining healthy. The results indicate that sex work, poverty, and health do not always have a paradoxical relationship.

Hold on: females modulate sperm depletion from storage sites in the fly Drosophila melanogaster.

PubMed

Bloch Qazi, Margaret C; Hogdal, Leah

2010-09-01

Among many species of insects, females gain fitness benefits by producing numerous offspring. Yet actions related to producing numerous offspring such as mating with multiple males, producing oocytes and placing offspring in sub-optimal environments incur costs. Females can decrease the magnitude of these costs by retaining gametes when suitable oviposition sites are absent. We used the pomace fly, Drosophila melanogaster, to explore how the availability of fresh feeding/oviposition medium influenced female fitness via changes in offspring survivorship and the modulation of gamete release. Availability of fresh medium affected the absolute number and temporal production of offspring. This outcome was attributable to both decreased larval survival under crowded conditions and to female modulation of gamete release. Direct examination of the number of sperm retained among the different female storage organs revealed that females 'hold on' to sperm, retaining more sperm in storage, disproportionately within the spermathecae, when exposed infrequently to fresh medium. Despite this retention, females with lower rates of storage depletion exhibited decreased sperm use efficiency shortly after mating. This study provides direct evidence that females influence the rate of sperm depletion from specific storage sites in a way that can affect both female and male fitness. The possible adaptive significance of selective gamete utilization by female Drosophila includes lowering costs associated with frequent remating and larval overcrowding when oviposition sites are limiting, as well as potentially influencing paternity when females store sperm from multiple males.

Phenotype-genotype correlation in potential female carriers of X-linked developmental cataract (Nance-Horan syndrome).

PubMed

Khan, Arif O; Aldahmesh, Mohammed A; Mohamed, Jawahir Y; Alkuraya, Fowzan S

2012-06-01

To correlate clinical examination with underlying genotype in asymptomatic females who are potential carriers of X-linked developmental cataract (Nance-Horan syndrome). An ophthalmologist blind to the pedigree performed comprehensive ophthalmic examination for 16 available family members (two affected and six asymptomatic females, five affected and three asymptomatic males). Facial features were also noted. Venous blood was collected for sequencing of the gene NHS. All seven affected family members had congenital or infantile cataract and facial dysmorphism (long face, bulbous nose, abnormal dentition). The six asymptomatic females ranged in age from 4-35 years old. Four had posterior Y-suture centered lens opacities; these four also exhibited the facial dysmorphism of the seven affected family members. The fifth asymptomatic girl had scattered fine punctate lens opacities (not centered on the Y-suture) while the sixth had clear lenses, and neither exhibited the facial dysmorphism. A novel NHS mutation (p.Lys744AsnfsX15 [c.2232delG]) was found in the seven patients with congenital or infantile cataract. This mutation was also present in the four asymptomatic girls with Y-centered lens opacities but not in the other two asymptomatic girls or in the three asymptomatic males (who had clear lenses). Lens opacities centered around the posterior Y-suture in the context of certain facial features were sensitive and specific clinical signs of carrier status for NHS mutation in asymptomatic females. Lens opacities that did not have this characteristic morphology in a suspected female carrier were not a carrier sign, even in the context of her affected family members.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

PubMed

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-03-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

Communication during sex among female bonobos: effects of dominance, solicitation and audience

PubMed Central

Clay, Zanna; Zuberbühler, Klaus

2012-01-01

Bonobo females frequently form close bonds, which give them social power over other group members. One potential mechanism to facilitate female bonding is the performance of sexual interactions. Using naturalistic observations and experiments, we found various patterns that determined female-female sexual interactions. First, while low-ranked females interacted with all females, sexual interactions between high-ranked females were rare. Second, during genital contacts, females sometimes produced ‘copulation calls’, which were significantly affected by the rank of the caller and partner, as well as the solicitation direction. Third, there was a significant effect of the alpha female as a bystander, while variables relating to physical experience had no effects. Overall, results highlight the importance of sexual interactions for bonobo female social relations. Copulation calls are an important tool during this process, suggesting that they have become ritualised, beyond their reproductive function, to serve as broader social signals in flexible and potentially strategic ways. PMID:22389761

Female Physicians and the Work-Family Conflict.

PubMed

Treister-Goltzman, Yulia; Peleg, Roni

2016-05-01

There has been a dramatic increase in the number of female physicians in all fields and specializations of medicine, but this increase has not resulted in a redistribution of domestic tasks and responsibilities. Reviewing the literature of the last two decades (April 1994 to April 2014) on how female physicians cope with the challenge of balancing their family and professional lives for the duration of their professional careers revealed that they suffer from the work-family conflict more than other professionals and that it has a more negative effect on women than on men. Women physicians consider work-family balance significantly when making career choices. These considerations affect their career success, their productivity as faculty members, their marital life, and parenthood. Having a supportive spouse at home and a facilitating mentor at work are important for a positive work-family balance among female physicians. Special career-supporting measures, such as flexible work schedules and expanded support for childcare over the course of work and when taking part in academic activities, are critical for female physicians.

The Recovering Female Alcoholic: A Family Affair.

ERIC Educational Resources Information Center

Rolls, Judith A.

To ensure a positive prognosis, the recovering female alcoholic requires family therapy as an adjunct to her regular treatment program. Research indicates that the characteristics affecting a person's ability to secure and use treatment include (1) predisposing factors; (2) attitudes toward alcohol and health care; (3) personal enabling factors;…

Adolescents' responses to the gender valence of cigarette advertising imagery: the role of affect and the self-concept.

PubMed

Shadel, William G; Niaura, Raymond; Abrams, David B

2004-12-01

The studies presented in this manuscript evaluated the role that affect and the self-concept play in adolescent never smokers' reactions to the gender valence of cigarette advertising imagery. Study 1 (n=29; 59% female) revealed that adolescent females have more positive affective reactions to female-valenced cigarette advertising imagery compared to male-valenced cigarette advertising imagery. Study 2 (n=101; 56% female) revealed that adolescent females viewed female-valenced cigarette advertising imagery as more relevant to their self-concepts compared to male-valenced cigarette advertising imagery. Across both studies, male adolescents did not respond differently as a function of the gender valence of cigarette advertising imagery. Thus, female-valenced cigarette advertising imagery may have specific effects on never smoking female adolescents by enhancing positive affect and suggesting that women who smoke hold the same characteristics as do the young women themselves.

Male risk taking, female odors, and the role of estrogen receptors.

PubMed

Kavaliers, Martin; Clipperton-Allen, Amy; Cragg, Cheryl L; Gustafsson, Jan-Åke; Korach, Kenneth S; Muglia, Louis; Choleris, Elena

2012-12-05

Male risk-taking and decision making are affected by sex-related cues, with men making riskier choices and decisions after exposure to either women or stimuli associated with women. In non-human species females and, or their cues can also increase male risk taking. Under the ecologically relevant condition of predation threat, brief exposure of male mice to the odors of a sexually receptive novel female reduces the avoidance of, and aversive responses to, a predator. We briefly review evidence showing that estrogen receptors (ERs), ERα and ERβ, are associated with the mediation of these risk taking responses. We show that ERs influence the production of the female odors that affect male risk taking, with the odors of wild type (ERαWT, ERβWT), oxytocin (OT) wildtype (OTWT), gene-deleted 'knock-out' ERβ (ERβKO), but not ERαKO or oxytocin (OT) OTKO or ovariectomized (OVX) female mice reducing the avoidance responses of male mice to cat odor. We further show that administration of specific ERα and ERβ agonists to OVX females results in their odors increasing male risk taking and boldness towards a predator. We also review evidence that ERs are involved in the mediation of the responses of males to female cues, with ERα being associated with the sexual and both ERβ and ERα with the sexual and social mechanisms underlying the effects of female cues on male risk taking. The implications and relations of these findings with rodents to ERs and the regulation of human risk taking are briefly considered. Copyright © 2012 Elsevier Inc. All rights reserved.

Male risk taking, female odors, and the role of estrogen receptors

PubMed Central

Kavaliers, Martin; Clipperton-Allen, Amy; Cragg, Cheryl L.; Gustafsson, Jan-Åke; Korach, Kenneth S.; Muglia, Louis; Choleris, Elena

2016-01-01

Male risk-taking and decision making are affected by sex-related cues, with men making riskier choices and decisions after exposure to either women or stimuli associated with women. In non-human species females and, or their cues can also increase male risk taking. Under the ecologically relevant condition of predation threat, brief exposure of male mice to the odors of a sexually receptive novel female reduces the avoidance of, and aversive responses to, a predator. We briefly review evidence showing that estrogen receptors (ERs), ERα and ERβ, are associated with the mediation of these risk taking responses. We show that ERs influence the production of the female odors that affect male risk taking, with the odors of wild type (ERαWT, ERβWT), oxytocin (OT) wildtype (OTWT), gene-deleted ‘knock-out’ ERβ (ERβKO), but not ERαKO or oxytocin (OT) OTKO or ovariectomized (OVX) female mice reducing the avoidance responses of male mice to cat odor. We further show that administration of specific ERα and ERβ agonists to OVX females results in their odors increasing male risk taking and boldness towards a predator. We also review evidence that ERs are involved in the mediation of the responses of males to female cues, with ERα being associated with the sexual and both ERβ and ERα with the sexual and social mechanisms underlying the effects of female cues on male risk taking. The implications and relations of these findings with rodents to ERs and the regulation of human risk taking are briefly considered. PMID:22472459

Fertility and Female Employment: Problems of Causal Direction.

ERIC Educational Resources Information Center

Cramer, James C.

1980-01-01

Considers multicollinearity in nonrecursive models, misspecification of models, discrepancies between attitudes and behavior, and differences between static and dynamic models as explanations for contradictory information on the causal relationship between fertility and female employment. Finds that initially fertility affects employment but that,…

Ovarian fluid allows directional cryptic female choice despite external fertilization

PubMed Central

Alonzo, Suzanne H.; Stiver, Kelly A.; Marsh-Rollo, Susan E.

2016-01-01

In species with internal fertilization, females can favour certain males over others, not only before mating but also within the female's reproductive tract after mating. Here, we ask whether such directional post-mating (that is, cryptic) female mate choice can also occur in species with external fertilization. Using an in vitro sperm competition experiment, we demonstrate that female ovarian fluid (ovarian fluid) changes the outcome of sperm competition by decreasing the importance of sperm number thereby increasing the relative importance of sperm velocity. We further show that ovarian fluid does not differentially affect sperm from alternative male phenotypes, but generally enhances sperm velocity, motility, straightness and chemoattraction. Under natural conditions, female ovarian fluid likely increases the paternity of the preferred parental male phenotype, as these males release fewer but faster sperm. These results imply females have greater control over fertilization and potential to exert selection on males in species with external fertilization than previously thought possible. PMID:27529581

The Nance-Horan syndrome: a rare X-linked ocular-dental trait with expression in heterozygous females.

PubMed

Bixler, D; Higgins, M; Hartsfield, J

1984-07-01

This report describes two families with the Nance-Horan syndrome, an X-linked trait featuring lenticular cataracts and anomalies of tooth shape and number. Previous reports have described blindness in affected males but posterior sutural cataracts with normal vision as the primary ocular expression in heterozygous females. In one of these two families, the affected female is not only blind in one eye but reportedly had supernumerary central incisors (mesiodens) removed. This constitutes the most severe ocular and dental expression of this gene in heterozygous females yet reported.

Predator odor exposure of rat pups has opposite effects on play by juvenile males and females

PubMed Central

Stockman, Sara L.; McCarthy, Margaret M.

2017-01-01

Juvenile social play behavior is one of the earliest sexually differentiated behaviors to emerge. In rats, as with most other species that play, males engage in more rough-and-tumble play compared to females. Exposure to early life adversity is a major driver of adult health and can manifest differently in males and females. However, the effects of adverse early life exposure on play behavior in the juvenile period are poorly understood. To address this, male and female neonatal rats were exposed to predator odor (PO), for 5 min/day on PN1-PN3. At the time of exposure to PO, both male and female pups suppressed ultrasonic vocalization and displayed more freezing behavior. Circulating corticosterone increased in males immediately following PO exposure but not in females. The enduring effects of PO exposure were opposite in males compared to females in that PO exposed males decreased social play, while PO exposed females increased play behavior compared to same sex controls. PO exposure did not significantly affect cell genesis in the neonatal dentate gyrus of either sex. PO exposure did not affect anxiety-like behavior assessed in the juvenile period or in adulthood, nor did it affect social interactions in adulthood. This work provides new insight into how sex may interact with adverse early life events to contribute to development of the social consequences of such exposures. PMID:27569603

Factors Affecting the Retention Decisions of Female Surface Warfare Officers