Clinical Outcomes of Assisted Reproductive Techniques Using Cryopreserved Gametes and Embryos in Human Medicine

The methods of cryopreservation play a key role in assisted reproductive technique (ART) treatments, as they increase the efficacy of the treatments by allowing banking of supernumerary embryos for later use. It has been recently proposed that these methods could also increase the safety of ART treatments, by reducing complications such as ovarian hyperstimulation during early pregnancy; thus, the policy of total freeze for later differed transfer of embryos has been proposed. Also of great importance, cryopreservation of oocytes and spermatozoa has permitted gamete storage for long term facilitating practical routines such as the gamete banking for third-party reproductive treatment. In this chapter, the clinical indications and treatment outcomes will be revised and data updated on the safety of using cryopreservation methods in ART treatments

Examining the Role of Instructor-Student Relationship Quality in Yoga: Implications for Participants’ Motives, Stress, Affect, and Mindfulness

Extensive research outlines a broad spectrum of physical and mental health benefits associated with participation in yoga. In particular, yoga can increase mindfulness as well as decrease anxiety, depression, and stress. However, knowledge of the underlying mechanisms and conditions for promoting positive outcomes requires further study. Limited research has examined how the quality of the relationship between the yoga student and instructor may influence potential health benefits derived from participation in yoga. The present study investigated associations between levels of stress, emotional well-being, motives for yoga, relationship quality, and mindfulness during yoga. Analysis of data collected from 219 adults indicated that higher levels of stress and negative emotional well-being increased the likelihood that yoga was practised to address psychological motives rather than perceived physical health benefits. Additionally, relationship quality with the instructor was found to predict greater state mindfulness during the yoga session. The present study highlights the importance of the relationship quality between instructor and student; future research investigating the efficacy of yoga in optimizing mental health should consider how health outcomes might be influenced by motives for participation and interpersonal relationships

Psychiatrically relevant signatures of domain-general decision-making and metacognition in the general population

Human behaviours are guided by how confident we feel in our abilities. When confidence does not reflect objective performance, this can impact critical adaptive functions and impair life quality. Distorted decision-making and confidence have been associated with mental health problems. Here, utilising advances in computational and transdiagnostic psychiatry, we sought to map relationships between psychopathology and both decision-making and confidence in the general population across two online studies (N’s = 344 and 473, respectively). The results revealed dissociable decision-making and confidence signatures related to distinct symptom dimensions. A dimension characterised by compulsivity and intrusive thoughts was found to be associated with reduced objective accuracy but, paradoxically, increased absolute confidence, whereas a dimension characterized by anxiety and depression was associated with systematically low confidence in the absence of impairments in objective accuracy. These relationships replicated across both studies and distinct cognitive domains (perception and general knowledge), suggesting that they are reliable and domain general. Additionally, whereas Big-5 personality traits also predicted objective task performance, only symptom dimensions related to subjective confidence. Domain-general signatures of decision-making and metacognition characterise distinct psychological dispositions and psychopathology in the general population and implicate confidence as a central component of mental health

Profiling the Influence of Gene Variants Related to Folate-Mediated One-Carbon Metabolism on the Outcome of In Vitro Fertilization (IVF) with Donor Oocytes in Recipients Receiving Folic Acid Fortification

Partial funding for open access charge: Universidad de MálagaNutritional status and gene polymorphisms of one-carbon metabolism confer a well-known interaction that in pregnant women may affect embryo viability and the health of the newborn. Folate metabolism directly impacts nucleotide synthesis and methylation, which is of increasing interest in the reproductive medicine field. Studies assessing the genetic influence of folate metabolism on IVF treatments have currently been performed in women using their own oocytes. Most of these patients seeking to have a child or undergoing IVF treatments are advised to preventively intake folate supplies that restore known metabolic imbalances, but the treatments could lead to the promotion of specific enzymes in specific women, depending on their genetic variance. In the present study, we assess the influence of candidate gene variants related to folate metabolism, such as Serine Hydroxymethyltransferase 1 SHMT1 (rs1979276 and rs1979277), Betaine-Homocysteine S-Methyltransferase BHMT (rs3733890), Methionine synthase reductase MTRR (rs1801394), Methylenetetrahydrofolate reductase MTHFR (rs1801131 and rs1801133), methionine synthase MTR (rs12749581), ATP Binding Cassette Subfamily B Member 1 ABCB1 (rs1045642) and folate receptor alpha FOLR1 (rs2071010) on the success of IVF treatment performed in women being recipients of donated oocytes. The implication of such gene variants seems to have no direct impact on pregnancy consecution after IVF; however, several gene variants could influence pregnancy loss events or pregnancy maintenance, as consequence of folic acid fortification.This research was funded by grant PTQ 09–01-00496, Ministerio de Economía y Competitividad (MINECO), Government of Spain, Instituto de Fertilidad Clínica Rincón y Fundación Rincón. AR Palomares and KA Rodriguez-Wallberg are supported by grants from the Swedish Research Council (VR Dnr 2021-06116, Dnr 2020–02230), the Swedish Cancer Society (CAN 2017/704, 20 0170 F) and Karolinska Institutet Research grants

The transcriptional coactivator MAML1 regulates p300 autoacetylation and HAT activity

MAML1 is a transcriptional coregulator originally identified as a Notch coactivator. MAML1 is also reported to interact with other coregulator proteins, such as CDK8 and p300, to modulate the activity of Notch. We, and others, previously showed that MAML1 recruits p300 to Notch-regulated genes through direct interactions with the DNA–CSL–Notch complex and p300. MAML1 interacts with the C/H3 domain of p300, and the p300–MAML1 complex specifically acetylates lysines of histone H3 and H4 tails in chromatin in vitro. In this report, we show that MAML1 potentiates p300 autoacetylation and p300 transcriptional activation. MAML1 directly enhances p300 HAT activity, and this coincides with the translocation of MAML1, p300 and acetylated histones to nuclear bodies

Hyperglycemia does not affect antigen specific activation and cytolytic killing by CD8+ T cells in vivo

Metabolism is of central importance to T cell survival and differentiation. It is well known that T cells cannot function in the absence of glucose, but it is less clear how they respond to excessive levels of glucose. In this study we investigated how increasing levels of glucose affect T cell-mediated immune responses. We examined the effects of increased levels of glucose on CD8⁺ T cell behaviour in vitro by assessing activation and cytokine production, as well as oxygen consumption rate, extracellular acidification rate and intracellular signalling. In addition, we assessed in vivo proliferation, cytokine production and cytolytic activity of cells in chemically induced diabetic C57BL6 mice. Elevated levels of glucose in in vitro cultures had modest effects on proliferation and cytokine production, while in vivo hyperglycemia had no effect on CD8⁺ T cell proliferation, interferon gamma production or cytolytic killing.This work was supported by the NC3Rs [grant number NC/M001083/1]; the BBSRC [grant number BB/M00015X/2]; the Leverhulme Trust [grant number EM-2015-030]; the Medical Research Council [grant number G0901155]; the Diabetes U.K. [grant number BDA 09/0003840]; the BBSRC-funded Midlands Integrative Biosciences Training Partnership (MIBTP) (K.B.); and the Lollipop Foundation (M.W. as the main grant applicant and A.R. as a co-applicant)

GSK3β is a negative regulator of the transcriptional coactivator MAML1

Glycogen synthase kinase 3β (GSK3β) is involved in several cellular signaling systems through regulation of the activity of diverse transcription factors such as Notch, p53 and β-catenin. Mastermind-like 1 (MAML1) was originally identified as a Notch coactivator, but has also been reported to function as a transcriptional coregulator of p53, β-catenin and MEF2C. In this report, we show that active GSK3β directly interacts with the MAML1 N-terminus and decreases MAML1 transcriptional activity, suggesting that GSK3β might target a coactivator in its regulation of gene expression. We have previously shown that MAML1 increases global acetylation of histones, and here we show that the GSK3 inhibitor SB41, further enhances MAML1-dependent histone acetylation in cells. Finally, MAML1 translocates GSK3β to nuclear bodies; this function requires full-length MAML1 protein

Activated Cdc42-associated kinase 1 (ACK1) binds the sterile α motif (SAM) domain of the adaptor SLP-76 and phosphorylates proximal tyrosines

The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a crucial role in T cell activation by linking antigen receptor (T cell receptor, TCR) signals to downstream pathways. At its N terminus, SLP-76 has three key tyrosines (Tyr-113, Tyr-128, and Tyr-145, "3Y") as well as a sterile α motif (SAM) domain whose function is unclear. We showed previously that the SAM domain has two binding regions that mediate dimer and oligomer formation. In this study, we have identified SAM domain-carrying non-receptor tyrosine kinase, activated Cdc42-associated tyrosine kinase 1 (ACK1; also known as Tnk2, tyrosine kinase non-receptor 2) as a novel binding partner of SLP-76. Co-precipitation, laser-scanning confocal microscopy, and in situ proximity analysis confirmed the binding of ACK1 to SLP-76. Further, the interaction was induced in response to the anti-TCR ligation and abrogated by the deletion of SLP-76 SAM domain (ΔSAM) or mutation of Tyr-113, Tyr-128, and Tyr-145 to phenylalanine (3Y3F). ACK1 induced phosphorylation of the SLP-76 N-terminal tyrosines (3Y) dependent on the SAM domain. Further, ACK1 promoted calcium flux and NFAT-AP1 promoter activity and decreased the motility of murine CD4(+) primary T cells on ICAM-1-coated plates, an event reversed by a small molecule inhibitor of ACK1 (AIM-100). These findings identify ACK1 as a novel SLP-76-associated protein-tyrosine kinase that modulates early activation events in T cells.This work was supported by Wellcome Trust Grant 092627/Z/10/Z (to C. E. R.

Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes : a randomised crossover trial

Data availability The data analysed during the current study are available from the corresponding author on reasonable request. Funding The authors are supported by grants from Novo Nordisk Foundation (NNF14OC0011493 and NNF14OC0009941), Swedish Diabetes Foundation (DIA2015-052), Wenner-Gren Foundation, Swedish Research Council (2015-00165), Strategic Research Program in Diabetes at Karolinska Institutet (2009-1068), Stockholm County Council (SLL20150517 and SLL20170159) and Swedish Heart Lung Foundation (20150423).Peer reviewedPublisher PD