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The neurodevelopmental disorders Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS) both arise from genomic alterations within human chromosome 15q11-q13. A deletion of the SNORD116 cluster, encoding small nucleolar RNAs, or frameshift mutations within MAGEL2 result in closely related phenotypes in individuals with PWS or SYS, respectively. By investigation of their subcellular localization, we observed that in contrast to a predominant cytoplasmic localization of wild-type (WT) MAGEL2, a truncated MAGEL2 mutant was evenly distributed between the cytoplasm and the nucleus. To elucidate regulatory pathways that may underlie both diseases, we identified protein interaction partners for WT or mutant MAGEL2, in particular the survival motor neuron protein (SMN), involved in spinal muscular atrophy, and the fragile-X-messenger ribonucleoprotein (FMRP), involved in autism spectrum disorders. The interactome of the non-coding RNA SNORD116 was also investigated by RNA-CoIP. We show that WT and truncated MAGEL2 were both involved in RNA metabolism, while regulation of transcription was mainly observed for WT MAGEL2. Hence, we investigated the influence of MAGEL2 mutations on the expression of genes from the PWS locus, including the SNORD116 cluster. Thereby, we provide evidence for MAGEL2 mutants decreasing the expression of SNORD116, SNORD115, and SNORD109A, as well as protein-coding genes MKRN3 and SNRPN, thus bridging the gap between PWS and SYS., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Delta-like homolog 1 ( Dlk1 ), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Experimental data presented here identify two independent regulatory mechanisms, transcriptional and translational, by which Ifrd1 (TIS7) and its orthologue Ifrd2 (SKMc15) regulate Dlk1 levels. Mice deficient in both Ifrd1 and Ifrd2 (dKO) had severely reduced adipose tissue and were resistant to high-fat diet-induced obesity. Wnt signaling, a negative regulator of adipocyte differentiation, was significantly upregulated in dKO mice. Elevated levels of the Wnt/β-catenin target protein Dlk1 inhibited the expression of adipogenesis regulators Pparg and Cebpa , and fatty acid transporter Cd36 . Although both Ifrd1 and Ifrd2 contributed to this phenotype, they utilized two different mechanisms. Ifrd1 acted by controlling Wnt signaling and thereby transcriptional regulation of Dlk1 . On the other hand, distinctive experimental evidence showed that Ifrd2 acts as a general translational inhibitor significantly affecting Dlk1 protein levels. Novel mechanisms of Dlk1 regulation in adipocyte differentiation involving Ifrd1 and Ifrd2 are based on experimental data presented here., Competing Interests: IV, DC, KP, TV, DH, RG, ME, IT, PE, ED, MH, VK, GD, JR, MK, MH, TV, LH No competing interests declared, (© 2023, Vietor et al.)

Here we describe two new species of the genus Penicillium section Torulomyces with solitary phialides. Penicillium poederi sp. nov . was isolated from volcanic soils in Iceland. Penicillium tirolense sp. nov . was isolated from a sporocarp of Serpula lacrymans. Both species are characterised by slow growth rates and the production of a brown soluble pigment on CYA, conidiophores with solitary ampulliform phialides with smooth-walled stipes and warty, globose conidia and with connectives without visible rings. The spores of. P. poederi are 2.5 μm diam, while the spores of P. tirolense are 2.0 μm diam. In a multigene phylogeny based on the ITS, BenA , CaM and RPB2 gene regions P. tubakianum and P. wollemiicola are the closest relatives of P. poederi. This species differs from P. tubakianum and P. wollemiicola by its growth rates and by its pigmentation. The holotype of P. poederi is IB2017/0007, while SF014017 (CBS 147622) is a culture derived from the holotype. The closest relatives of P. tirolense are P. austricola and P. riverlandense. It differs from P. austricola Kirchmair M, Embacher J, Heimdörfer D, Walch G, Neuhauser S (2022). P. riverlandense by lower growth rates and the absence of growth at 37 °C. The holotype of P. tirolense is IBF2019/0162, while SF015108 (CBS 147625) is a culture derived from the holotype. Citation: Kirchmair M, Embacher J, Heimdörfer D, Walch G, Neuhauser S (2022). Penicillium poederi and Penicillium tirolense, two new species of section Torulomyces . Fungal Systematics and Evolution 10 : 91-101. doi: 10.3114/fuse.2022.10.03., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest., (© 2022 Westerdijk Fungal Biodiversity Institute.)

RNA modifications are crucial factors for efficient protein synthesis. All classes of RNAs that are involved in translation are modified to different extents. Recently, mRNA modifications and their impact on gene regulation became a focus of interest because they can exert a variety of effects on the fate of mRNAs. mRNA modifications within coding sequences can either directly or indirectly interfere with protein synthesis. In order to investigate the roles of various natural occurring modified nucleotides, we site-specifically introduced them into the coding sequence of reporter mRNAs and subsequently translated them in HEK293T cells. The analysis of the respective protein products revealed a strong position-dependent impact of RNA modifications on translation efficiency and accuracy. Whereas a single 5-methylcytosine (m⁵C) or pseudouridine () did not reduce product yields, N ¹-methyladenosine (m¹A) generally impeded the translation of the respective modified mRNA. An inhibitory effect of 2' O -methlyated nucleotides (Nm) and N ⁶-methyladenosine (m⁶A) was strongly dependent on their position within the codon. Finally, we could not attribute any miscoding potential to the set of mRNA modifications tested in HEK293T cells., Competing Interests: The authors declare no conflicts of interest.

Introduction: Delayed initial antifungal therapy is associated with high mortality rates caused by invasive candida infections, since accurate detection of the opportunistic pathogenic yeast and its identification display a diagnostic challenge. diagnosis of candida infections relies on time-consuming methods such as blood cultures, serologic and histopathologic examination. to allow for fast detection and characterization of invasive candidiasis, there is a need to improve diagnostic tools. trends in diagnostics switch to non-culture-based methods, which allow specified diagnosis within significantly shorter periods of time in order to provide early and appropriate antifungal treatment. Areas covered: within this review comprise novel pathogen- and host-related testing methods, e.g. multiplex-PCR analyses, T2 magnetic resonance, fungus-specific DNA microarrays, microRNA characterization or analyses of IL-17 as biomarker for early detection of invasive candidiasis. Expert commentary: Early recognition and diagnosis of fungal infections is a key issue for improved patient management. As shown in this review, a broad range of novel molecular based tests for the detection and identification of Candida species is available. However, several assays are in-house assays and lack standardization, clinical validation as well as data on sensitivity and specificity. This underscores the need for the development of faster and more accurate diagnostic tests.