#peg3

[hello-bellasmith]

Bromoacetamido-PEG3-azide

[nadiamarti]

The story of the South Asheville Cemetery's rich history and the ongoing effort to restore this valuable cultural landmark. Film produced by Nadia Marti (Warren Wilson College '16) and Gabrielle Holodnak (Warren Wilson College '17).

[leedsomics]

Comparative proteomics of vesicles essential for the egress of Plasmodium falciparum gametocytes from red blood cells

Transmission of malaria parasites to the mosquito is mediated by sexual precursor cells, the gametocytes. Upon entering the mosquito midgut, the gametocytes egress from the enveloping erythrocyte while passing through gametogenesis. Egress follows an inside-out mode during which the membrane of the parasitophorous vacuole ruptures prior to the erythrocyte membrane. Membrane rupture requires the exocytosis of specialized secretory vesicles of the parasites; i.e. the osmiophilic bodies (OBs) involved in rupturing the parasitophorous vacuole membrane, and vesicles (here termed g-exonemes) that harbour the perforin-like protein PPLP2 required for erythrocyte lysis. While several OB proteins are known, like G377 and MDV1/Peg3, the protein composition of the g-exonemes remains unclear. Here, we used high-resolution imaging and BioID methods to study the two types of egress vesicles in Plasmodium falciparum gametocytes. We show that OB exocytosis precedes discharge of the g-exonemes and that exocytosis of the g-exonemes, but not of the OBs, is calcium-sensitive. Further, the two types of vesicles exhibit distinct proteomes. In addition to known egress-related proteins, our analyses revealed novel components of OBs and g-exonemes, including proteins involved in vesicle trafficking. Our data provide insight into the immense molecular machinery required for the inside-out egress of P. falciparum gametocytes. http://dlvr.it/Sj9xQR

[olejfevang]

Wool/cashmere on wool, cold weather is here🌤 . . . . . . . . #morris#morrisstockholm#gransasso#rolexoysterdate#rolex#tomford#jacobcohen#jacobcohenjeans#rmwilliams#bergen#norway (ved Bergen, Hordaland) https://www.instagram.com/p/B3VSCA-pEg3/?igshid=x0vvykrg8tvg

[dreddymd]

Dad’s Life Experiences May Epigenetically Influence His Children’s Health

Mothers have often – unfortunately and unfairly – had to carry the burden of being “to blame” for any of their child’s health-related shortcomings. When pregnant women are advised: eat more of this but not too much of that, drink this but definitely none of that… why does dad get off scot-free amid these typically well-intentioned suggestions?

Previous studies have, for example, epigenetically linked dad’s drinking to his son’s sensitivity and preference for alcohol and connected a father’s diet to negative pregnancy outcomes. Research has even hinted that stressed-out fathers could epigenetically set-up his son for high blood sugar later in life. A review article conducted at Georgetown University Medical Center and published in the American Journal of Stem Cell shows that both mothers and fathers contribute to their offspring’s health via epigenetic alterations. It seems like common sense that both parents contribute to their child’s health, but science has only just begun to demonstrate it, according to Joanna Kitlinska, PhD, an associate professor in biochemistry, and molecular and cellular biology at Georgetown University. “We know the nutritional, hormonal and psychological environment provided by the mother permanently alters organ structure, cellular response and gene expression in her offspring,” she said. “But our study shows the same thing to be true with fathers – his lifestyle, and how old he is, can be reflected in molecules that control gene function. In this way, a father can affect not only his immediate offspring, but future generations as well.”

The review takes into consideration a wide range of evidence, looking at the effects of paternal preconception exposures – such as paternal diet, exposure to toxins, and psychosocial stress – on the child’s health via epigenetic mechanisms. This collection of animal and human studies investigating epigenetic marks of interest, including DNA methylation, histone modification and miRNA expression, provides evidence of the link between fathers’ experiences and heritable epigenetic programming.

For instance, a child can have fetal alcohol spectrum disorder (FASD) even if the mother never drank alcohol. Kitlinska explained, “Up to 75 percent of children with FASD have biological fathers who are alcoholics, suggesting that preconceptual paternal alcohol consumption negatively impacts their offspring.”

Among the numerous studies assessed, investigators found evidence associating increased paternal age with abnormal social interaction in mice offspring. In another, they found that a lack of food at a young age was associated with marked epigenetic changes. Specifically, “low amounts of dietary resources during the father’s pre-adolescence was correlated with a lower chance of cardiovascular mortality in his offspring,” hinting that a father’s diet while he’s young may epigenetically impact his child’s and grandchild’s risk of cardiovascular disease and death later in life. Additional studies suggest a father’s obesity can impact his child’s likelihood for developing diseases like diabetes or experiencing abnormal metabolic regulation. They found that “paternal obesity is linked with hypomethylation at the differentially methylated regions (DMR) of the IGF2 gene.” This epigenetic modification leads to an increase in IGF2 proteins, which are, in turn, linked to obesity. Children of obese fathers were shown to have “hypomethylation in their MEST, PEG3, and NNAT DMRs,” which can result in “enlargement of adipocytes, changes in metabolic regulation, diabetes, rhabdomyosarcoma, glioma, and obesity,” the researchers reported. DNA methylation is a common, well-known epigenetic mechanism defined by the addition of a methyl group to DNA, predominantly attaching to cytosine residues. This epigenetic modification restricts the expression of genes. However, hypomethylation is characterized by a lack of methylation, thereby increasing the expression of genes.

Other studies reported an epigenetic connection between a father’s exposure to toxicants, like smoking and irradiation, and his child’s genome. Irradiation has previously been “correlated with decreased viability in murine offspring.” They discovered that male mice exposed to irradiation had less de novomethyltransferase, DNA methyltransferase 3a (DNMT3a), and hypomethylation of long and short nuclear elements. They indicated that “these epigenetic changes lead to detrimental effects on somatic thymus tissue in the progeny of exposed mice.”

Additional evidence investigating a father’s alcohol consumption on his child’s health suggests that this behavior could epigenetically decrease newborn birth weight, reduce brain size, and impair cognitive function. This evidence contributes to the growing body of evidence on epigenetic mechanisms that may play a role in fetal alcohol spectrum disorders (FASDs). Researchers are still investigating the specific modifications that can lead to these changes, but they have found that epigenetic marks in sperm DNA can be transferred to the offspring. Overall, numerous experiments indicate that a father’s early exposures and habits, such as smoking, drinking, or diet, may epigenetically impact his child’s health. Perhaps this new scientific revelation will ease society’s pressures on mothers and take into consideration the effect both parents’ lifestyles may have on their children, among many other factors.

“This new field of inherited paternal epigenetics needs to be organized into clinically applicable recommendations and lifestyle alternations,” Kitlinska said. “And to really understand the epigenetic influences of a child, we need to study the interplay between maternal and paternal effects, as opposed to considering each in isolation.”

Bailey Kirkpatrick

Source: Day, J., Savani, S., Krempley, B.D., Nguyen, M., Kitlinska, J.B. (2016). Influence of paternal preconception exposures on their offspring: through epigenetics to phenotype. Am J Stem Cells, 5(1):11-18. (pdf)

Reference: Georgetown University Medical Center. Review finds fathers’ age, lifestyle associated with birth defects. EurekAlert. 15 May 2016. Web.

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Marijuana Use May Epigenetically Impact Sperm Health

Fluoride’s Epigenetic Effect on Bone Development

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[rnomics]

Circular #RNA identified from Peg3 and Igf2r

by Bambarendage P. U. Perera, Subash Ghimire, Joomyeong Kim Circular #RNA is a newly discovered class of non-coding #RNA generated through the back-splicing of linear pre-#mRNA. In the current study, we characterized two circular #RNAs that had been identified through NGS-based 5’RACE experiments. According to the results, the Peg3 locus contains a 214-nucleotide-long circular #RNA, circPeg3, that is detected in low abundance from the neonatal brain, lung and ovary. In contrast, the Igf2r locus contains a group of highly abundant circular #RNAs, circIgf2r, showing multiple forms with various exon combinations. In both cases, the expression patterns of circPeg3 and circIgf2r among individual tissues are quite different from their linear #mRNA counterparts. This suggests potential unique roles played by the identified circular #RNAs. Overall, this study reports the identification of novel circular #RNAs specific to mammalian imprinted loci, suggesting that circular #RNAs are likely involved in the function and regulation of imprinted genes. http://bit.ly/2p7jwNV

[mariebenz]

Genes From Dad Influence How Mom Cares for Babies

MedicalResearch.com Interview with:

Professor Rosalind John Head of Biomedicine Division, Professor School of Biosciences Cardiff University Cardiff UK MedicalResearch.com: What is the background for this study? What are the main findings?  Response: I have been studying a really remarkable family of genes called “imprinted genes” for the last 20 years. For most genes, we inherit two working copies -- one from our mother and one from our father. But with imprinted genes, we inherit only one working copy – the other copy is switched off by epigenetic marks in one parent’s germline. This is really odd because we are all taught at school that two copies of a gene are important to protect us against mutations, and much safer than only one copy. So why turn off one copy?

Maternal care boosted by paternal imprinting in mammals When my research group were studying these genes in mice, we found out that one of them, called Phlda2, plays an important role in the placenta regulating the production of placental hormones. Placental hormones are critically important in pregnancy as they induce adaptations in the mother required for healthy fetal growth. There was also some indirect evidence that placental hormones play a role in inducing maternal instinct. Women are not born with a maternal instinct -  this behaviour develops during pregnancy to prepare the mother-to-be for the new and demanding role of caring for her baby. This led to my idea that this gene expressed in the offspring’s placenta could influence maternal behaviour, which was entirely novel.  Until now direct experimental evidence to support the theory that placental hormones trigger this “motherly love” by acting directly on the brain of the mother has been lacking. To test the theory that our imprinted gene could influence the mother’s behaviour by regulating placental hormones, we generated pregnant mice by IVF carrying embryos with different copies of Phlda2. We used IVF to keep all the mothers genetically identical. This resulted in genetically identical pregnant female mice exposed to different amounts of placental hormones – either low, normal or high. We found that female mice exposed in pregnancy to low amounts of placental hormones were much more focused on nest building (housekeeping) and spent less time looking after their pups or themselves than normal mice. In contrast, female mice exposed to high placental hormones neglected their nests and spent more time looking after their pups and more time self-grooming. We also found changes in the mother’s brain before the pups were born so we know that the change in priorities started before birth.  MedicalResearch.com: What should readers take away from your report? Response: This study is important because it shows, for the first time, that genes from the dad expressed in the placenta influence the quality of care mothers gives to their offspring. Perhaps more significantly, this study highlights the importance of a fully functional placenta for high quality maternal care. We have shown in a mouse model that genes in the placenta and placental hormones are important for priming maternal nurturing in an animal model. Human placenta have the same imprinted genes and also manufactures placental hormones. It is possible that problems with the placenta could misprogram maternal nurturing in a human pregnancy and these mothers may not bond well with their newborn. It is also possible that problems with the placenta could contribute to depression in mothers. We are all familiar with postnatal depression but many more mothers experience depression in pregnancy with 1 in 7 mothers reporting clinically significant symptoms.  MedicalResearch.com: What recommendations do you have for future research as a result of this work?  Response: After we found out that Phlda2 could influence maternal behaviour in mice, we asked whether there were changes in this gene in human placenta from pregnancies where women were either diagnosed with clinical depression or self reported depression in pregnancy. Phlda2 seems to be OK but we found another gene that belongs to the same imprinted gene family called PEG3 that is expressed at lower than normal levels in women with depression. Strangely, this seems to only be in placenta from boys.  MedicalResearch.com: Is there anything else you would like to add? Response: To explore this further, we have just started our own human cohort study called “Grown in Wales” at Cardiff University focused on prenatal depression. We are now looking at placental hormones in the mother’s blood and gene expression in the placenta to test the idea that the genes we are studying in mice are misregulated in the placenta of pregnancies where the mothers suffer with depression. This work is now funded by the Medical Research Council. Citation:  Maternal care boosted by paternal imprinting in mammals D. J. Creeth, G. I. McNamara,, S. J. Tunster, R. Boque-Sastre,, B. Allen,, L. Sumption, J. B. Eddy,A. R. Isles, R. M. John PLOS Published: July 31, 2018 https://doi.org/10.1371/journal.pbio.2006599   The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article

[blessedby-puberty]

Peg Leg || Open

Hiccup had secluded himself from the rest of the carnival for the past few weeks. He had been so wrapped up in the new born cubs, he forgot completely about social interaction. But he didn't need that, he didn't need people..So he always reminded himself. 

He sat now in the cage where the cubs were, and smiled to himself. They had opened their eyes by now, and each of them had developed their own personality. The fact that Hiccup could be so close to them, bond with them, blew his mind. He knew that everyone thought he was nuts, he could tell just by the way they watched him with the animals. He didn't know why, but he had always had a special gift with the animals. One that no one else in the entire carnival had.  He never worried about an incident happening, or him getting hurt..Simply because he trusted the animals. All of them. Even his biggest cat, Trixie.

He leaned back, resting on the cage, and watched as the fattest cub wabbled towards him. He let out a chuckle and watched as it started sniffing his leg..Well..The fake one. The chunky cat began to paw at it, and Hiccup knew it wouldn't be good. "Please don't bite that." He mumbled, readjusting himself. He was sure that no one was around, beings he hadn't seen any body in about a week. He pulled his pant leg up, reveling his fake leg,  and slowly removed it. "Not today, bud." He whispered to the cat, setting the leg down beside him.

This was the only time he had taken the leg off outside of his car. Normally he was so self conscious about it, he didn't want anyone to know that it wasn't real. But here with the cubs, that didn't matter. He smiled softly as the chunk laid its head on his stump, closing it's eyes slowly and yawning. He was beginning to think that maybe he could take a nap, as well. That was until he heard rustling behind him. 

"Who's there?!" He called out frantically, torn between waking the cub up to fix his leg, or to let it sleep. Exposing himself. 

[a-crooked-stick]

This is a stereo mix of an eight channel recording made by Groupe de Recherches Musicales of a live performance with sound projection via the Acousmonium sound system. http://www.presenceselectroniques.ch/ http://en.wikipedia.org/wiki/Acousmonium