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Aneuploidy in oocytes is a leading cause of implantation failure, miscarriage and congenital disorders. During meiosis, proper timing of chromosome segregation is regulated by the spindle assembly checkpoint (SAC) and the anaphase-promoting complex/cyclosome (APC/C). However, how pharmacological manipulation of these regulatory pathways affects aneuploidy remains incompletely understood. In this study, we investigated whether SAC inhibition by reversine induces aneuploidy in mouse oocytes and whether partial inhibition of APC/C by proTAME can alleviate these errors. Germinal vesicle (GV) oocytes were matured in vitro in the presence of various concentrations of reversine. To optimize the timing of treatment, oocytes were exposed to reversine for 0, 3, 5 or 7 h, followed by culture with or without proTAME. A proTAME-only group (2.5 nM) was also included. Chromosome spreads were analyzed at the metaphase II (MII) stage to determine aneuploidy rates. Reversine (5 nM) yielded an MII maturation rate of 80.5% but induced a high aneuploidy rate of 77.0%. Sequential treatment with 2.5 nM proTAME significantly reduced aneuploidy to 33.3%. In contrast, proTAME alone led to 79.0% aneuploidy, suggesting its effect is contingent upon prior SAC disruption. These results indicate that reversine compromises chromosomal integrity, while appropriately timed, low-dose proTAME can partially rescue segregation errors. Our findings underscore the potential of pharmacologically regulating APC/C activity to reduce aneuploidy and enhance oocyte quality, offering new avenues for improving outcomes in assisted reproductive technologies.
The term “embodied knowledge” is often used as if its meaning is evident, and as if there is clarity about the relations it brings into view. The bodies in motion of the kumina festival Tambufest tell us about the forms of collective world-building that exist outside of but in relation to the juridical structures of sovereignty that govern modern Western political and social life.
Autism Spectrum Disorder (ASD) is defined as a unidimensional condition, and autism traits are measured on a continuum where the high end of the spectrum represents individuals likely to have an ASD diagnosis. However, the large heterogeneity of ASD has thrown this unidimensional conceptualization into question. With the exact underlying cause(s) of autism yet to be identified, there is a pressing need to establish core, underlying dimensions of ASD that can capture heterogeneity within the autism spectrum, thereby better specifying both autistic traits and ASD symptoms. Here we describe one important transdiagnostic dimension, the cognitive rigidity-flexibility dimension, that may impact autistic traits and symptoms across symptom-relevant cognitive domains. We first discuss how diminished cognitive flexibility manifests in core autistic traits and autism symptoms in perception, attention, learning, social cognition, and communication. We then propose to supplement assessments of autistic traits in the general population and autism symptoms in individuals with an ASD diagnosis with a comprehensive batter of cognitive flexibility measures in these symptom-relevant domains. We conjecture that systematic differences in domain-general versus domain-specific cognitive flexibility can distill subgroups within the autism phenotype. While we focus on the cognitive flexibility dimension here, we believe that it is important to extend this framework to other higher order dimensions that can capture core autism symptoms and transdiagnostic symptom severity. This approach can characterize the latent, multi-faceted structure of autism, thereby yielding greater precision in diagnostic classification and the creation of more targeted interventions.
Alcohol use disorders (AUDs) often coexist with psychotic disorders. Both are common and each can cause or perpetuate the other. Comorbid diagnoses are multifactorial in origin, and both diagnostically and therapeutically challenging. This article is a narrative review of the epidemiology, diagnosis and management of comorbid AUDs and psychotic disorders. Although there is a lack of robust evidence on many aspects of this association, AUDs have been repeatedly shown to worsen outcomes in individuals with schizophrenia. The importance of a rigorous approach to diagnosis is emphasised. Three main treatment strategies emerge: considering particular antipsychotic drugs, relapse-prevention medication and engagement with a number of psychosocial interventions.
This article examines the connections between existing democratic deficits in law and contemporary democratic backsliding processes. To undermine the democratic process, present-day autocrats employ various legal strategies, including enacting new legal institutions (such as constitutional amendments or key statutory reforms) or manipulating existing ones. Focusing on a legal legacy of military rule in Turkey, the Specially Authorized Courts, this study argues that in consolidating power, autocrats also capitalize on pre-existing authoritarian zones within legal systems. In Turkey’s case, the AKP government has leveraged the exceptional procedures of Specially Authorized Courts to silence adversaries while simultaneously framing its reforms to the structure of these courts and the trials held at these courts as efforts to democratize the country and eradicate authoritarian legacies. As a result, the AKP masked its repressive actions behind a narrative of democratization in the early stages of Turkey’s democratic regression. Overall, the article presents both the coercive and legitimating uses of pre-existing “zones of authoritarianism” in law in contemporary processes of democratic backsliding. In doing this, it highlights how aspiring autocrats exploit the histories embedded in legal institutions to obscure their repressive actions.
This research communication hypothesizes that superstimulation with follicle-stimulating hormone (FSH) would not impact behavior and performance of Holstein cows. The objectives were to investigate the effect of FSH superstimulation on follicular dynamics, animal behaviour, body surface temperature and milk yield of Holstein cows. Cows were blocked by parity and body condition score (BCS), and within a block, they were assigned randomly to receive either normal saline (CON = 7) or 500 IU of FSH (n = 8). The estrous cycle of cows was synchronized by using two injections of prostaglandin F2-alpha (PG), 11 days apart. The dominant follicle was ablated at the time of the second PG injection, and an intra-vaginal controlled internal drug release (CIDR) was inserted (day 0). Two days later, FSH treatment was initiated and continued for 3 days in six equal doses of 83.33 IU after 12 h. Follicles were counted and their sizes were measured from day-0 to day-5. Behavior, including activity and feeding time, was recorded using SmartTag Neck from day 0 to 6. The surface temperatures of the eye, shoulder, flank, and vulva were measured by using infrared thermal imaging every 12 h from day-2 to day-5. Milk was recorded from day-0 to day-6. Mixed effects models were used to analyse the data using SAS statistical software. The number of small and medium follicles did not differ between treatments. However, FSH-treated cows had a more (P = 0.01) large and total follicles compared with CON cows. FSH treatment did not affect activity, feeding time, body surface temperature, or milk yield. In conclusion, FSH superstimulation increased the number of large follicles but did not influence behaviour, body surface temperature, or performance in dairy cows.
Given two graphs G and H, the Ramsey number $R(G,H)$ is the smallest positive integer N such that every graph of order N contains G or its complement contains H as a subgraph. Let $C_n$ denote the cycle on n vertices and let $tW_{2m+1}$ denote the disjoint union of t copies of the $(2m+2)$-vertex wheel $W_{2m+1}$. We show that for integers $m\ge 1$, $t\ge 2$ and $n\ge (6m+3)t-6m+999$,
This result extends several previous results and settles a conjecture posed by Sudarsana [‘A note on the Ramsey number for cycle with respect to multiple copies of wheels’, Electron. J. Graph Theory Appl.9(2) (2021), 561–566].
For young people with eating disorders (EDs), family-based therapy (FBT) is generally recommended as first-line treatment. Although there is an abundance of evidence demonstrating the efficacy of FBT, less than half of young people achieve full remission with this treatment. Enhanced cognitive behaviour therapy (CBT-E) is an established alternative to FBT, demonstrating effectiveness in individuals who have not achieved full remission with FBT. It is also recommended when family therapy is unacceptable, contraindicated, or ineffective. Despite some overlap – particularly in addressing maintaining factors and prioritising weight normalisation – the two treatments diverge significantly in conceptualisation of the eating disorder, proposed mechanisms of action, role of both young people and parents, and strategies and processes of therapy. These differences may contribute to one treatment being effective where the other has not, but can present challenges and difficulties for the young person, family and clinician when transitioning from FBT to CBT-E. In this paper, we provide guidance for clinicians delivering CBT-E with young people who have a history of FBT treatment. We highlight common issues encountered among this cohort, discuss how they can present a barrier to successful implementation of CBT-E, and describe solutions.
Key learning aims
(1) To learn the commonly encountered barriers to treatment when implementing CBT-E for young people who have previously engaged in FBT.
(2) To learn strategies to overcome these barriers focusing on the young person, parents and multi-disciplinary team.
Politicians appeal to social groups to court their electoral support. However, quantifying which groups politicians refer to, claim to represent, or address in their public communication presents researchers with challenges. We propose a supervised learning approach for extracting group mentions from political texts. We first collect human annotations to determine the passages of a text that refer to social groups. We then fine-tune a transformer language model for contextualized supervised classification at the word level. Applied to unlabeled texts, our approach enables researchers to automatically detect and extract word spans that contain group mentions. We illustrate our approach in two applications, generating new empirical insights into how British parties use social groups in their rhetoric. Our method allows for detecting and extracting mentions of social groups from various sources of texts, creating new possibilities for empirical research in political science.