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While the cohesin complex is a key player in genome architecture, how it localizes to specific chromatin sites is not understood. Recently, we and others have proposed that direct interactions with transcription factors lead to the localization of the cohesin-loader complex (NIPBL/MAU2) within enhancers. Here, we identify two clusters of LxxLL motifs within the NIPBL sequence that regulate NIPBL dynamics, interactome, and NIPBL-dependent transcriptional programs. One of these clusters interacts with MAU2 and is necessary for the maintenance of the NIPBL-MAU2 heterodimer. The second cluster binds specifically to the ligand-binding domains of steroid receptors. For the glucocorticoid receptor (GR), we examine in detail its interaction surfaces with NIPBL and MAU2. Using AlphaFold2 and molecular docking algorithms, we uncover a GR-NIPBL-MAU2 ternary complex and describe its importance in GR-dependent gene regulation. Finally, we show that multiple transcription factors interact with NIPBL-MAU2, likely using interfaces other than those characterized for GR.

Major Depressive Episode (MDE) is one of the most common psychiatric disorders. Often difficult to treat, this disease is one of the leading causes of suicide. A recent study showed an association between GPR56/ADGRG1 mRNA, MDE and response to antidepressant treatment in blood and in brain. Among GPR56 splicing variant, the S4 isoform has recently been associated with microglial synaptic pruning, while microglia are already known as a central player in MDE. Therefore, we hypothesized that S4 is the specific isoform associated to MDE and antidepressant response. To test our hypothesis, an in silico analysis was first performed to identify the different proteins and transcript isoforms of GPR56. This analysis allowed to design PCR and qPCR primers. GPR56 total, S4 and S3 were assessed by RT-qPCR in leukocytes from a cohort of 46 MDE patients including non-responders (NR, n = 31) and responders-remitters (R, n = 17) to antidepressant treatment. We replicated the result of one of our previous studies, which described an increase in total GPR56 mRNA in Rs. Additionally, we observed that this variation differs among mRNA splicing variants, with S4 exhibiting a similar pattern of variation while S3 shows no significant change. The differences observed withstood statistical correction for covariates of interest such as smoking, gender and suicidal ideation, demonstrating the robustness of the model. These findings confirm our hypothesis that certain mRNA splicing variants of GPR56 may play a more significant role in depression. This study highlighted a link between the GPR56-S4 and response to antidepressant treatment., Competing Interests: Conflict of Interest None of the authors has any actual or potential conflict of interest, financial, personal or other relationship with any other person or organization in the three years prior to the commencement of this study that could inappropriately influence, or be perceived to influence, our work., (Copyright © 2025. Published by Elsevier B.V.)

Introduction: Recruitment of participants for intervention studies is challenging. We evaluated the effectiveness and efficiency of a participant recruitment campaign through an online registry for the FINGER-NL study, a multi-domain lifestyle intervention trial targeting cognitively healthy individuals aged 60-79 with dementia prevention potential. Additionally, we explored which recruitment strategy successfully reached individuals from underrepresented groups in research., Methods: The campaign entailed seven recruitment strategies referring to The Dutch Brain Research Registry (DBRR): (1) Facebook advertisements, (2) appearance on national television, (3) newspaper articles, (4) researcher outreach, (5) patient organizations, (6) search engines, and (7) other. For each strategy, we describe the number of individuals (a) registered, (b) potentially eligible, and (c) included in FINGER-NL. Subsequently, the efficiency, defined by the eligibility ratio (eligible/registered), and effectiveness, defined by the inclusion ratio (included/registered) were calculated. Associations between recruitment strategies and sociodemographic factors of underrepresented groups were tested with binomial logistic regressions., Results: The campaign resulted in 13,795 new DBRR registrants, of which n  = 3475 were eligible (eligibility ratio = 0.25) and n  = 1008 were included (inclusion ratio = 0.07). The Facebook advertisements and television appearance resulted in the highest numbers of registrants ( n  = 4678 and n  = 2182) which translated to the highest number of inclusions ( n  = 288 and n  = 262). The appearance on national television (eligibility ratio = 0.35), newspaper articles (0.26), and Facebook campaigns (0.26) were the most efficient strategies. The national television appearance (inclusion ratio = 0.13) was the most effective strategy. The Facebook campaign and appearance on national television performed relatively better in recruiting individuals from underrepresented groups., Discussion: A multipronged recruitment campaign via a national online recruitment registry is efficient and effective in recruiting and prescreening an adequate number of individuals aged 60-79 years with prevention potential for a multi-site intervention trial within a limited time frame of 15 months. Social media advertisements and television are preferred strategies to recruit individuals from underrepresented groups., Highlights: An online brain research registry recruited eligible participants successfully.Mass media recruitment strategies are efficient for reaching large numbers.Direct recruitment through researchers and patient organizations seems more effective.Online registries offer automated prescreening and alternatives for screen-failures.Tailored strategies are needed to reach underrepresented groups to improve diversity., Competing Interests: S.A.M.S. provided consultancy services to Prothena Biosciences, Aribio, and Biogen, and she is part of the Scientific Advisory Board of Cogstate. All funds are paid to the institution. W.M.F. has performed contract research for Biogen MA Inc, and Boehringer Ingelheim. W.M.F. has been an invited speaker at Biogen MAInc, Danone, Eisai, Novonordisk, Web MD Neurology (Medscape), Springer Healthcare, European Brain Council. W.M.F. is consultant to Oxford Health Policy Forum CIC, Roche, Eisai, and Biogen MA Inc. W.M.F. participated on advisory boards of Biogen MAI inc, Roche, and EliLilly. All funding is paid to her institution. W.M.F. is a member of the steering committee of PAVE, and Think Brain Health. W.M.F. was associate editor of Alzheimer, Research & Therapy in 2020/2021. W.M.F. is associate editor at Brain. M.D.Z. is site coordinator of the phase 1/2 ASPIRE‐FTD clinical trial (NCT06064890) sponsored by AviadoBio. L.W., L.M.S., S.B., Y.M., O.R., N.S., J.M.O., E.S., K.D., Y.V.,R.A.A.H., and S.K. report no conflicts of interest. Author disclosures are available in the Supporting Information., (© 2025 The Author(s). Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Desolvation processes, though common in self-assembled biological structures, are rarely evidenced and utilized in the design of crystalline architectures. In this study, we introduce a novel approach using the [Mo 8 S 8 O 8 (OH) 8 (guest)] 2- complex, formed by the self-condensation of four [Mo V 2 O 2 S 2 ] 2- fragments around a guest unit (Mo VI O 6 H 4 or oxalate), as a chaotropic scaffold for crystallizing hybrid organic-inorganic systems with natural cyclodextrins. Our findings reveal that β-cyclodextrin (β-CD) facilitates the formation of host-guest complexes, while α-cyclodextrin (α-CD) induces the formation of a Kagome-type structure with significant voids. These new compounds were thoroughly characterized using X-ray diffraction (both powder and single-crystal), N 2 adsorption, elemental and thermogravimetric analysis. Additionally, solution studies using 1 H NMR titration and small-angle X-ray scattering (SAXS) demonstrated pre-association of the building units in solution. These results enhance our understanding of the design principles for supramolecular structures composed of inorganic polyanions and cyclodextrins., (© 2024 Wiley-VCH GmbH.)