microRNAs play critical roles in the survival and recovery of Caenorhabditis elegans from starvation-induced L1 diapause

Laura explains that you are to imagine a scenario where you would anticipate feeling that without alcohol/drinking, it would be incomplete, not fun, boring etc. She writes about a practice she learned in therapy, a form of written visualization, where you play two different tapes forward (hmm… I thought there was only one…). A life of freedom and rid of the toxicity that drives us further and further away from who we really are. What playing the tape forward does is remind me. Reduction-of-function mutation (rf) in the age-1/PI3 kinase gene, age-1(hx546), made worms long-lived in the L1 starvation assay and was able to suppress the reduced L1 survival rate of mir-71(lf); the rate of the double mutants was comparable to that of wild type (Fig. 2A). In worms that recovered from 4 d of L1 starvation, we also found that a significant portion of the mir-71(lf) mutants displayed egg-laying defects and overproliferating or precociously reflexed gonads. (A) The mir-71(n4115, lf) mutant displayed severe reduction in L1 starvation survival rate, and the reduced survival rate of mir-71(lf) was suppressed by a reduction-of-function allele of age-1(hx546). To investigate the roles of miRNAs in animal survival during starvation-induced L1 diapause, we impaired the overall miRISC function with loss-of-function (lf) mutants of ain-1 (ku322, ku425, and tm3681) and ain-2(tm2432) and examined their L1 starvation survival rate (Materials and Methods). To test the hypothesis revery play that these developmental timing genes mediate the regulatory role of miR-71 in larval development during recovery from starvation-induced L1 diapause, we examined whether knocking down HBL-1 function can suppress the retarded VPC timing defect of mir-71(lf). Note that the daf-16(lf) worms recovering from 3 d of L1 starvation displayed a ∼12-h delay in overall development and that the mir-71(lf); daf-16(lf) double mutants displayed an ∼24-h delay.

• Peer support interventions are now recognised as valuable components of mental health recovery.
• At Khiron Clinics, we see support groups as one strand in a wider web of care.
• For examining the age-1 3′UTR reporter, the rol-6(d) marker (100 ng/μl pRF4) was used instead of the unc-119(+) plasmid.
• To compare the survival rates between strains, we simulated the survival rate of each genotype to 100 arbitrary “individual worms” and performed the log-rank test in Graphpad Prism 4.
• MiR-71 represses the expression of age-1 and unc-31 through the actions on their 3′UTR, but miR-71 is not required for arresting M cell division during L1 diapause.

What If I Don’t Meet Division I Standards?

Given my views on play, you won’t be surprised to learn that I asked the presenters about whether play experiences could qualify as the kinds of responsive, positive, engaged, and empowering interactions they described. I was attending professional development aimed at helping library staff support families from refugee backgrounds, and we were discussing the role that libraries and childcare staff (mostly the latter, based on the mix of the group) can play in helping often highly traumatised communities. A small increase in risk of harm, replicated many times on a massive scale, means harm is certainly occurring. As COVID-19 lockdowns unfolded around the world, and sales of games, puzzles, toys, and other playful artforms spiked, a friend asked me if I felt a sense of validation. And worst of all, a combination of the two, where other players essentially become supporting cast for a scripted victory that is neither earned, nor fun, nor remotely playful – a psychodrama rather than a game, toying with their victims rather than playing with them. Controlling bullies who insist everyone play their way, forcing people to make deals they don’t want and to keep playing even when they aren’t having fun. MiR-71 regulates vulval cell division during recovery of starved L1 worms. We thus asked whether miR-71 was required for the reinitiation of developmental programs during the recovery phase after L1 starvation. These results indicate that miR-71 is not essential for arresting seam cell or M-cell divisions during L1 diapause, suggesting that miR-71 function is distinct from DAF-16 function. DAF-16 (the FOXO homolog in C. elegans) has been shown to play an important role in cell cycle arrest and developmental progression partly by promoting cki-1 expression in some somatic cells during L1 arrest (2). S1A indicated a dominant role of intestinal miRNAs in regulating L1 starvation survival. Writing it out, playing both tapes forward, as plain as day on paper, did wonderful things. One who loves spending time with their family during the holidays and cooking delicious meals, despite the stress it sometimes brings on. The space for me to, for the first time in my adult life, truly decide how I want to live.

Years of Play, 2 Weeks of Recovery, and EA Support just sent me a “Coming Soon” brochure.

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Play, Happiness, Imagination, Learning

For more information on recovering your account, visit the guide below. Group therapy can complement one-to-one work or serve as a transitional phase between intensive support and independent living. Support groups can be a place to feel heard, supported, and gently accompanied as you take steps forward. At Khiron Clinics, we see support groups as one strand in a wider web of care. For many, they are the first place where isolation begins to soften and hope feels possible again. These sessions complement individual therapy and help create a sense of containment, safety, and continuity. These models are used not just in clinical care but in recovery college programmes, self help groups, and community-based services across the UK. Peer support interventions are now recognised as valuable components of mental health recovery. This mix of professional oversight and personal connection helps create a balanced group dynamic where people feel supported emotionally and practically. This is when people who have faced similar mental health challenges share their stories and offer mutual encouragement. Over time, participants often find that being part of a group helps them build confidence, improve communication, and better understand their own needs in recovery. The reporter is strongly expressed in H and V cells in both wild-type and mir-71(lf) worms. Because miRNA-mediated gene silencing may cause translational inhibition or mRNA degradation or both (19), the relatively small increase of UNC-31 in mir-71(lf) animals was still consistent with unc-31 being a target of miR-71. To test whether the activity of the InsR pathway was down-regulated by miR-71, we first examined the endogenous expression of components of the InsR pathway in mir-71(lf). (C) The poor survival rate of daf-16(mu86, null) was enhanced by mir-71(lf). There may be one (or more) that are uncomfortable or downright piss you off. Stacking together concepts, ideas, and ways of coping that don’t include alcohol as a way to navigate to a better life and get closer to our true selves. There are as many ​ways to live free of drugs ​and alcohol as there are ​stories of successful sober ​people. Create your account and connect with a world of communities. Let us help you or your loved one begin their healing process and regain control of their life. If someone you know has struggled with alcohol and drug addiction, we want to support you in your recovery journey today. Addiction can strain family relationships. It will help family members from falling into pitfalls that hinder the recovery process of their loved one. Understanding these roles can help the family navigate recovery more effectively. The family’s role can be pivotal, no matter the kind of addiction and recovery on the horizon. The coordinated entrance into developmental arrest, long-term survival, and the reinitiation of development upon food availability are important biological processes to investigate. Different organisms have developed versatile growth arrest strategies to overcome starvation-induced metabolic and developmental problems. Food deprivation is a life-threatening challenge that animals frequently face as individuals and as species. Numerous animal species across multiple phyla enter developmental arrest for long-term survival in unfavorable environments and resume development upon stress removal. Contributed new reagents/analytic tools; X.Z., R.Z., and M.H.

• Mental health recovery doesn’t happen in isolation, it affects and involves others too.
• Instead, many specific physiological functions, such as the starvation-induced stress response, are regulated by a miRNA-target network, often involving multiple miRNAs and a large number of their targets.
• And as we’ve discussed above, simply offering the kind of safe, supported opportunities to play that we’d want to offer anyway is enough to create that space for healing.
• Have there been any changes to your account details that you didn’t make (email address, Activision ID, etc.)?
• But from a colour management and overall interpretation viewpoint, I don’t know what to do with this image, and to be honest, I like the hues you’ve achieved in the sky.
• On the other hand, the role of a particular miRNA (miR-71) is executed by repressing the expression of many genes in multiple pathways.

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L1 Starvation Survival Assay and Statistical Analysis.

We further examined worms recovering from 4 d of L1 starvation and found that around 90% of the mir-71(lf) mutants displayed retarded vulval precursor cell (VPC) division, compared with less than 5% in wild type (Fig. 4A). In contrast, the nuclear-localized GFP expression under the control of the 3′UTR of age-1(Fig. 3 C and D) or unc-31 (Fig. 3 E and F) was strongly repressed in the control worms, but prominently derepressed in mir-71(lf) mutant worms. If the 3′UTR of age-1 or unc-31 is repressed by miR-71, the GFP expression will be repressed in tissues where miR-71 is expressed in wild-type worms, but derepressed in the same tissues of mir-71(lf) worms. Among short-lived miRNA mutants, a mir-71 deletion mutant, mir-71(n4115) (referred to as mir-71(lf) hereafter), displayed a severe reduction in L1 starvation survival rate (Table S1 and Fig. 2A). Upon entering L1 diapause, RNA polymerase II quickly accumulates and pauses at promoter regions, and this accumulation was speculated to stop transcription and facilitate the immediate reinitiation of gene expression when food becomes available (2). Previous studies showed that the release of postdocking calcium-regulated dense-core vesicles, the insulin receptor (InsR) pathway, the AMPK pathway, and protein chaperones are required for the long-term survival of starved L1 worms (2–4). However, when newly hatched L1 worms encounter an environment with no food, developmental programs arrest and the worm enters L1 diapause. The presented results indicate that interactions between multiple miRNAs and likely a large number of their mRNA targets in multiple pathways regulate the response to starvation-induced L1 diapause. And we need to take seriously that, just as people’s literary diet matters, so does their ludic diet. In fact I still have a ton to say, about play anxiety and devaluation of play, which I’ll have to put into separate posts over the next few days. Furthermore, worms that are long-lived due to dietary restriction or decreased mitochondrial respiratory rates are short-lived during L1 diapause, suggesting that the mechanisms controlling L1 starvation survival are different at least in some aspects from those controlling aging (3). We provide evidence that miRNA miR-71 is not required for the animals’ entry into L1 diapause, but plays a critical role in long-term survival by repressing the expression of insulin receptor/PI3K pathway genes and genes acting downstream or in parallel to the pathway. We need to be promoting better-quality games that do more to help people have fun, and we need to be modelling and making room for healthy play that promotes pro-social behaviour. That means running programs, preferably having staff who can teach the games, having services that help people find others who can teach and/or are interested in playing, and establishing norms for play in the library space in the hopes of (a) offering that safe, and potentially healing, interaction; (b) having those norms spread. I recommend turning it off to see how it impacts this specific image. In normally exposed images, this method can lead to oversaturation, so I usually reduce it using other modules like Color Balance RGB. The LAB tone curve is mostly me experimenting to see how it affects color saturation, particularly in the Blue and Magenta spectrum, which I often adjust. I’m fighting for a reimbursement, but I’m posting this so you don’t lose the resources I did.” Support isn’t just unhelpful; they aren’t even in the same reality as the players. “To the people calling me an ‘EA Spokesman’—take a look at my latest interaction with them. This study is supported by National Institutes of Health Grant GM47869 (to M.H.).