Although a number of imprinted genes are known to be highly expressed in the brain, and in certain brain regions in particular, whether they are truly over-represented in the brain has never been ...formally tested. Using thirteen single-cell RNA sequencing datasets we systematically investigated imprinted gene over-representation at the organ, brain region, and cell-specific levels.
We established that imprinted genes are indeed over-represented in the adult brain, and in neurons particularly compared to other brain cell-types. We then examined brain-wide datasets to test enrichment within distinct brain regions and neuron subpopulations and demonstrated over-representation of imprinted genes in the hypothalamus, ventral midbrain, pons and medulla. Finally, using datasets focusing on these regions of enrichment, we identified hypothalamic neuroendocrine populations and the monoaminergic hindbrain neurons as specific hotspots of imprinted gene expression.
These analyses provide the first robust assessment of the neural systems on which imprinted genes converge. Moreover, the unbiased approach, with each analysis informed by the findings of the previous level, permits highly informed inferences about the functions on which imprinted gene expression converges. Our findings indicate the neuronal regulation of motivated behaviours such as feeding and sleep, alongside the regulation of pituitary function, as functional hotspots for imprinting. This adds statistical rigour to prior assumptions and provides testable predictions for novel neural and behavioural phenotypes associated with specific genes and imprinted gene networks. In turn, this work sheds further light on the potential evolutionary drivers of genomic imprinting in the brain.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
2.
Long term review of laparoscopic sacrocolpopexy Higgs, P.J.; Chua, H.‐L.; Smith, A.R.B.
BJOG : an international journal of obstetrics and gynaecology,
August 2005, Letnik:
112, Številka:
8
Journal Article
Recenzirano
Objective Assessment of long term outcome following laparoscopic sacrocolpopexy.
Design Retrospective follow up study using standardised examination with pelvic organ prolapse quantification system ...(POP‐Q) and questionnaires.
Setting A tertiary urogynaecology unit in the North West of England.
Population One hundred and forty consecutive cases who had a laparoscopic sacrocolpopexy at St Mary's Hospital, Manchester, between 1993 and 1999.
Methods Women completed questionnaires and were examined in gynaecology clinic or sent postal questionnaires if unable to attend the clinic.
Main outcome measures Adequacy of vault support and recurrent vaginal prolapse assessed by POP‐Q score. Assessment of prolapse, urinary and bowel symptoms and sexual function using questionnaires.
Results One hundred and three women were contacted after a median of 66 months. Sixty‐six women were examined and a further 37 women filled in questionnaires only. Recurrent vault prolapse occurred in 4 of the 66 women who were examined. Prolapse had recurred or persisted in 21 of 66 women, with equal numbers of anterior and posterior vaginal wall prolapse. Overall, 81/102 (79%) said that their symptoms of prolapse were ‘cured’ or ‘improved’; 39/103 (38%) still had symptoms of prolapse. For every two women who were cured of their urinary or bowel symptoms, one woman developed worse symptoms.
Conclusions Among the 66 women available for examination laparoscopic sacrocolpopexy provided good long term support of the vault in 92%. Forty‐two percent of these women had recurrent vaginal wall prolapse. Despite this, 79% of women felt that their symptoms of prolapse were cured or improved following surgery.
Imprinted genes are subject to germline epigenetic modification resulting in parental-specific allelic silencing. Although genomic imprinting is thought to be important for maternal behaviour, this ...idea is based on serendipitous findings from a small number of imprinted genes. Here, we undertook an unbiased systems biology approach, taking advantage of the recent delineation of specific neuronal populations responsible for controlling parental care, to test whether imprinted genes significantly converge to regulate parenting behaviour. Using single-cell RNA sequencing datasets, we identified a specific enrichment of imprinted gene expression in a recognised "parenting hub", the galanin-expressing neurons of the preoptic area. We tested the validity of linking enriched expression in these neurons to function by focusing on MAGE family member L2 (Magel2), an imprinted gene not previously linked to parenting behaviour. We confirmed expression of Magel2 in the preoptic area galanin expressing neurons. We then examined the parenting behaviour of Magel2-null(+/p) mice. Magel2-null mothers, fathers and virgin females demonstrated deficits in pup retrieval, nest building and pup-directed motivation, identifying a central role for this gene in parenting. Finally, we show that Magel2-null mothers and fathers have a significant reduction in POA galanin expressing cells, which in turn contributes to a reduced c-Fos response in the POA upon exposure to pups. Our findings identify a novel imprinted gene that impacts parenting behaviour and, moreover, demonstrates the utility of using single-cell RNA sequencing data to predict gene function from expression and in doing so here, have identified a purposeful role for genomic imprinting in mediating parental behaviour.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cultured
are predominantly aerobic soil inhabitants, characterized by their highly coordinated predation and cellular differentiation capacities. Little is currently known regarding yet-uncultured
...from anaerobic, nonsoil habitats. We analyzed genomes representing one novel order (o__JAFGXQ01) and one novel family (f__JAFGIB01) in the
from an anoxic freshwater spring (Zodletone Spring) in Oklahoma, USA. Compared to their soil counterparts, anaerobic
possess smaller genomes and a smaller number of genes encoding biosynthetic gene clusters (BGCs), peptidases, one- and two-component signal transduction systems, and transcriptional regulators. Detailed analysis of 13 distinct pathways/processes crucial to predation and cellular differentiation revealed severely curtailed machineries, with the notable absence of homologs for key transcription factors (e.g., FruA and MrpC), outer membrane exchange receptor (TraA), and the majority of sporulation-specific and A-motility-specific genes. Further, machine learning approaches based on a set of 634 genes informative of social lifestyle predicted a nonsocial behavior for Zodletone
. Metabolically, Zodletone
genomes lacked aerobic respiratory capacities but carried genes suggestive of fermentation, dissimilatory nitrite reduction, and dissimilatory sulfate-reduction (in f_JAFGIB01) for energy acquisition. We propose that predation and cellular differentiation represent a niche adaptation strategy that evolved circa 500 million years ago (Mya) in response to the rise of soil as a distinct habitat on Earth.
The phylum
is a phylogenetically coherent bacterial lineage that exhibits unique social traits. Cultured
are predominantly aerobic soil-dwelling microorganisms that are capable of predation and fruiting body formation. However, multiple yet-uncultured lineages within the
have been encountered in a wide range of nonsoil, predominantly anaerobic habitats, and the metabolic capabilities, physiological preferences, and capacity of social behavior of such lineages remain unclear. Here, we analyzed genomes recovered from a metagenomic analysis of an anoxic freshwater spring in Oklahoma, USA, that represent novel, yet-uncultured, orders and families in the
. The genomes appear to lack the characteristic hallmarks for social behavior encountered in
genomes and displayed a significantly smaller genome size and a smaller number of genes encoding biosynthetic gene clusters, peptidases, signal transduction systems, and transcriptional regulators. Such perceived lack of social capacity was confirmed through detailed comparative genomic analysis of 13 pathways associated with
social behavior, as well as the implementation of machine learning approaches to predict social behavior based on genome composition. Metabolically, these novel
are predicted to be strict anaerobes, utilizing fermentation, nitrate reduction, and dissimilarity sulfate reduction for energy acquisition. Our results highlight the broad patterns of metabolic diversity within the yet-uncultured
and suggest that the evolution of predation and fruiting body formation in the
has occurred in response to soil formation as a distinct habitat on Earth.
Undulatory underwater swimming (UUS) is one of the major skills contributing to performance in competitive swimming. UUS has two phases- the upbeat is performed by hip extension and knee flexion, and ...the downbeat is the converse action. The purpose of this study was to determine which kinematic variables of the upbeat and downbeat are associated with prone UUS performance in an elite sample. Ten elite participants were filmed performing three prone 20 m UUS trials. Seven landmarks were manually digitised to calculate eighteen kinematic variables, plus the performance variable- horizontal centre of mass velocity (V
COM
). Mean V
COM
was significantly correlated with body wave velocity (upbeat r = 0.81, downbeat r = 0.72), vertical toe velocity (upbeat r = 0.71, downbeat r = 0.86), phase duration (upbeat r = −0.79), peak hip angular velocity (upbeat r = 0.73) and mean knee angular velocity (upbeat r = −0.63), all significant at P < 0.05. A multiple stepwise regression model explained 78% of variance in mean V
COM
. Peak toe velocity explained 72% of the variance, and mean body wave velocity explained an additional 6%. Elite swimmers should strive for a high peak toe velocity and a fast caudal transfer of momentum to optimise underwater undulatory swimming performance.
Imprinted genes are expressed from one parental allele as a consequence of epigenetic processes initiated in the germline. Consequently, their ability to influence phenotype depends on their ...parent-of-origin. Recent research suggests that the sex of the individual expressing the imprinted gene is also important. We have previously reported that genetically wildtype (WT) dams carrying and caring for pups mutant for
exhibit anxiety-like behaviours and their mutant pups show a reduction in ultrasonic vocalisation when separated from their mothers. Sex-specificity was not examined.
WT female mice were mated with WT, heterozygous
or homozygous
studs to generate all WT (control), 50:50 mixed or 100% mutant litters, respectively, followed by behavioural assessment of both dams and their pups.
We reproduced our original finding that WT dams carrying and caring for 100% mutant litters exhibit postpartum anxiety-like symptoms and delayed pup retrieval. Additionally, these WT dams were found to allocate less time to pup-directed care behaviours relative to controls. Male
-deficient pups demonstrated significantly reduced vocalisation with a more subtle communication deficit in females. Postweaning, male mutants exhibited deficits across a number of key social behaviours as did WT males sharing their environment with mutants. Only modest variations in social behaviour were detected in experimental females.
We have experimentally demonstrated that
deficiency confined to the offspring causes anxiety in mouse mothers and atypical behaviour including deficits in communication in their male offspring. A male-specific reduction in expression
in the fetally-derived placenta has previously been associated with maternal depression in human pregnancy. Maternal mood disorders such as depression and anxiety are associated with delays in language development and neuroatypical behaviour more common in sons.
deficiency could drive the association of maternal and offspring behavioural disorders reported in humans.
The animal purpose questionnaire (APQ) is a new instrument to measure human attitudes to animal use systematically across both species and purpose of use. This offers a more fine-grained approach to ...our understanding of how the belief in a specific animal's mental capacities relates to (dis-)agreement with their use for different human purposes. In the present study, 317 participants completed an online survey containing the APQ and the belief in animal mind (BAM) scale in a species-specific format, to test the prediction that levels of (dis-)agreement with animal use should mirror participants' judgements of animal sentience. The results obtained with the APQ confirmed that attitudes to animal use differed significantly across both purpose and species. Key findings included a relatively greater concern for dolphins and dogs over chimpanzees (suggesting that phylogenetic position is not the only determinant of attitudes to animal use). Across the purposes examined, respondents were largely negative about animal usage, with the exception that there was less disagreement if this was for medical research. Participants were also asked to provide demographic details such as gender and dietary preference. Regression analyses revealed high predictive power for species-specific BAM across five different kinds of animal use. General BAM scores, non-meat-eating and being female accounted for 31.5% of the total variability in APQ scores. The results indicate that BAM is a strong predictor of self-reported attitudes for using particular animals. However, the results showed some exceptions in the case of culturally typical 'produce' animals.
The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines, managing patients with food allergy (FA) in the community, intend to provide guidance to ...reduce the risk of accidental allergic reactions to foods in the community. This document is intended to meet the needs of early‐childhood and school settings as well as providers of non‐prepackaged food (e.g., restaurants, bakeries, takeaway, deli counters, and fast‐food outlets) and targets the audience of individuals with FA, their families, patient organizations, the general public, policymakers, and allergists. Food allergy is the most common trigger of anaphylaxis in the community. Providing children and caregivers with comprehensive information on food allergen avoidance and prompt recognition and management of allergic reactions are of the utmost importance. Provision of adrenaline auto‐injector devices and education on how and when to use these are essential components of a comprehensive management plan. Managing patients at risk of anaphylaxis raises many challenges, which are specific to the community. This includes the need to interact with third parties providing food (e.g., school teachers and restaurant staff) to avoid accidental exposure and to help individuals with FA to make safe and appropriate food choices. Education of individuals at risk and their families, their peers, school nurses and teachers as well as restaurant and other food retail staff can reduce the risk of severe/fatal reactions. Increased awareness among policymakers may improve decision‐making on legislation at local and national level.
Nitrogen excretion is of particular concern on dairy farms, not only because of its effects on water quality, but also because of the subsequent release of gases such as ammonia to the atmosphere. To ...manage N excretion, accurate estimates of urinary N (UN) and fecal N (FN) are needed. On commercial farms, directly measuring UN and FN is impractical, meaning that quantification must be based on predictions rather than measured data. The purpose of this study was to use a statistical approach to develop equations and evaluate the Cornell Net Carbohydrate and Protein System's (CNCPS) ability to predict N excretion in lactating dairy cows, and to compare CNCPS predictions to other equations in the literature. Urinary N was over-predicted by the CNCPS due to inconsistencies in N accounting within the model that partitioned more N to feces than urine, although predicted total N excretion was reasonable. Data to refine model predictions were compiled from published studies (n=32) that reported total collection N balance results. Considerable care was taken to ensure the data included in the development data set (n=104) accounted for >90% of the N intake (NI). Unaccounted N for the compiled data set was 1.47±4.60% (mean ± SD). The results showed that FN predictions could be improved by using a modification of a previously published equation: FN (g/d) = NI (g/kg of organic matter) × (1 – 0.842) + 4.3 × organic matter intake (kg/d) × 1.20, which, when evaluated against the compiled N balance data, had a squared coefficient of determination based on a mean study effect RMP2 of 0.73, concurrent correlation coefficient (CCC) of 0.83 and a root mean square error (RMSE) of 10.38g/d. Urinary N is calculated in the CNCPS as the difference between NI and other N excretion and losses. Incorporating the more accurate FN prediction into the current CNCPS framework and correcting an internal calculation error considerably improved UN predictions (RMSE = 12.73 g/d, RMP2=0.86, CCC=0.90). The changes to FN and UN translated into an improved prediction of total manure N excretion (RMSE = 12.42 g/d, RMP2=0.96, CCC=0.97) and allows nutritionists and farm advisors to evaluate these factors during the ration formulation process.
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