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We investigated the effects of 2-methoxyestradiol (2-ME), a promising new antitumor agent, on viable cell number and nuclear morphology of malignant glioma cells (three human and one rat glioma cell lines) and analyzed the controversial role of death recepor 5 (DR5) upregulation in 2-ME induced apoptosis. Microtiter-tetrazolium (MTT) assays showed a significant reduction of viable cells after incubation with 2 µM and 20 µM 2-ME for 48 and 72 hours in all cultures. In the 20 µM concentration, there were even significant effects in the majority of shorter incubation periods. Hoechst 33258 stains showed a substantial amount of cells with nuclear fragmentation indicating a late stage of apoptosis after 20 µM 2-ME treatments of 24 hours and more. The role of the DR5-mediated extrinsic apoptotic pathway was further studied in the three human glioma cell lines; 50 ng/ml of the DR5 ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and 2 µM 2-ME showed no synergism, as determined by MTT assays. Real-time PCR revealed no significantly increased amount of DR5 mRNA, suggesting that receptor upregulation does not play a major role for 2-ME-induced apoptosis in glioma cells, in contrast to data for a breast cancer cell line in the literature. [ABSTRACT FROM AUTHOR]

The article looks at the weather conditions during the 2009 expedition of the research vessel, Polarstern to a productive region of the Antarctic Circumpolar Current (ACC). The weather during the first days after the vessel left Cape Town, South Africa was dominated by a low pressure system with conditions improving after two days. Weather conditions when the vessel sailed towards a position north of South Georgia in order to observe another eddy in the southern ocean are described. Severe storms hit the area by the end of February which created a turbulent atmosphere. Wind force is discussed as the scientific work wrapped up and headed for Punta Arenas, Chile.

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Social recognition is essential for the formation of social structures. Many times, recognition comes with lesser exploration of familiar animals. This lesser exploration has led to the assumption that recognition may be a habituation memory. The underlying memory mechanisms and the thereby acquired cortical representations of familiar mice have remained largely unknown, however. Here, we introduce an approach directly examining the recognition process from volatile body odors among male mice. We show that volatile body odors emitted by mice are sufficient to identify individuals and that more salience is assigned to familiar mice. Familiarity is encoded by reinforced population responses in two olfactory cortex hubs and communicated to other brain regions. The underlying oxytocin-induced plasticity promotes the separation of the cortical representations of familiar from other mice. In summary, neuronal encoding of familiar animals is distinct and utilizes the cortical representational space more broadly, promoting storage of complex social relationships., (© 2024. The Author(s).)

Interleukin-11 (IL-11) is a member of the IL-6 family of cytokines and is an important factor for bone homeostasis. IL-11 binds to and signals via the membrane-bound IL-11 receptor (IL-11R, classic signaling) or soluble forms of the IL-11R (sIL-11R, trans-signaling). Mutations in the IL11RA gene, which encodes the IL-11R, are associated with craniosynostosis, a human condition in which one or several of the sutures close prematurely, resulting in malformation of the skull. The biological mechanisms of how mutations within the IL-11R are linked to craniosynostosis are mostly unexplored. In this study, we analyze two variants of the IL-11R described in craniosynostosis patients: p.T306_S308dup, which results in a duplication of three amino-acid residues within the membrane-proximal fibronectin type III domain, and p.E364_V368del, which results in a deletion of five amino-acid residues in the so-called stalk region adjacent to the plasma membrane. The stalk region connects the three extracellular domains to the transmembrane and intracellular region of the IL-11R and contains cleavage sites for different proteases that generate sIL-11R variants. Using a combination of bioinformatics and different biochemical, molecular, and cell biology methods, we show that the IL-11R-T306_S308dup variant does not mature correctly, is intracellularly retained, and does not reach the cell surface. In contrast, the IL-11R-E364_V368del variant is fully biologically active and processed normally by proteases, thus allowing classic and trans-signaling of IL-11. Our results provide evidence that mutations within the IL11RA gene may not be causative for craniosynostosis and suggest that other regulatory mechanism(s) are involved but remain to be identified., (© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Craniosynostosis is characterized by the premature fusion and ossification of one or more of the sutures of the calvaria, often resulting in abnormal features of the face and the skull. In cases in which growth of the brain supersedes available space within the skull, developmental delay or cognitive impairment can occur. A complex interplay of different cell types and multiple signaling pathways are required for correct craniofacial development. In this study, we report on two siblings with craniosynostosis and a homozygous missense pathogenic variant within the IL11RA gene (c.919 T > C; p.W307R). The patients present with craniosynostosis, exophthalmos, delayed tooth eruption, mild platybasia, and a basilar invagination. The p.W307R variant is located within the arginine-tryptophan-zipper within the D3 domain of the IL-11R, a structural element known to be important for the stability of the cytokine receptor. Expression of IL-11R-W307R in cells shows impaired maturation of the IL-11R, no transport to the cell surface and intracellular retention. Accordingly, cells stably expressing IL-11R-W307R do not respond when stimulated with IL-11, arguing for a loss-of-function mutation. In summary, the IL-11R-W307R variant, reported here for the first time to our knowledge, is most likely the causative variant underlying craniosynostosis in these patients., (© 2023. Springer Nature Limited.)

Our goal in this manuscript is to advance the assessment and treatment of monkey species in neuroscience research. We hope to begin a discussion and establish baseline data on how complications are identified and treated. We surveyed the neuroscience research community working with monkeys and compiled responses to questions about investigator demographics, assessment of animal wellbeing, treatment choices, and approaches to mitigate risks associated with CNS procedures and promote monkey health and wellbeing. The majority of the respondents had worked with nonhuman primates (NHP) for over 15 y. Identification of procedure-related complications and efficacy of treatment generally rely on common behavioral indices. Treatments for localized inflammatory responses are generally successful, whereas the treatment success for meningitis or meningoencephalitis, abscesses, and hemorrhagic stroke are less successful. Behavioral signs of pain are treated successfully with NSAIDs and opioids. Our future plans are to collate treatment protocols and develop best practices that can be shared across the neuroscience community to improve treatment success rates and animal welfare and therefore science. Human protocols can be used to develop best practices, assess outcomes, and promote further refinements in treatment practices for monkeys to enhance research outcomes.

The COP9 signalosome (CSN) and cullin-RING ubiquitin ligases (CRLs) form latent CSN-CRL complexes detectable in cells. We demonstrate that the CSN variants CSN CSN7A and CSN CSN7B preferentially bind to CRL3 or CRL4A and CRL4B, respectively. Interestingly, the interacting protein ubiquitin-specific protease 15 exclusively binds to latent CSN CSN7A -CRL3, while p27 KIP attaches to latent CSN CSN7B -CRL4A complex. Inhibition of deneddylation by CSN5i-3 or neddylation by MLN4924 do not impede the formation of latent complexes. Latent CSN CSN7A -CRL3 and latent CSN CSN7B -CRL4A/B particles are essential for specific cellular functions. We found that curcumin-induced cell death requires latent CSN CSN7B -CRL4A. Knockout of CSN7B in HeLa cells leads to resistance against curcumin. Remarkably, the small GTPase RAB18 recruits latent CSN CSN7A -CRL3 complex to lipid droplets (LDs), where CRL3 is activated by neddylation, an essential event for LD formation during adipogenesis. Knockdown of CSN7A or RAB18 or destabilization of latent complexes by cutting off CSN7A C-terminal 201-275 amino acids blocks adipogenesis., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)