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The widespread distribution and environmental impact of microplastics (MPs) have been a global challenge for several decades. There is an increasing interest in the dissemination, impact, and determination of MPs in the environment. Some reviews have emphasized the cause and effect of MPs, while others have reported on analytical techniques for their identification and quantification. However, there is still a research gap in the global distribution-impact evaluation of MPs. This review highlights the global distribution of MPs and their effects on humans and the ecosystem. Furthermore, we have classified the analytical techniques for the identification and quantification of MPs into three groups: traditional, post-traditional, and advanced. Having addressed the global distribution-impact analysis, we also presented some possible approaches for the removal of MPs including degradation and the use of biodegradable plastic substitutes. Lastly, we suggested perspectives for improving analyses, coverage, and sustainable approach toward MPs pollution control., Author(s): Kingsley I. John [sup.1] [sup.2] , Martins O. Omorogie [sup.3] [sup.4] [sup.5] , Aderemi T. Adeleye [sup.6] , Ajibola A. Bayode [sup.3] , Brigitte Helmreich [sup.5] Author Affiliations: (1) [...]

The concept of induced protein degradation by small molecules has emerged as a promising therapeutic strategy that is particularly effective in targeting proteins previously considered 'undruggable.' Thalidomide analogs, employed in the treatment of multiple myeloma, stand as prime examples. These compounds serve as molecular glues, redirecting the CRBN E3 ubiquitin ligase to degrade myeloma-dependency factors, IKZF1 and IKZF3. The clinical success of thalidomide analogs demonstrates the therapeutic potential of induced protein degradation. Beyond molecular glue degraders, several additional modalities to trigger protein degradation have been developed and are currently under clinical evaluation. These include heterobifunctional degraders, polymerization-induced degradation, ligand- dependent degradation of nuclear hormone receptors, disruption of protein interactions, and various other strategies. In this Review, we will provide a concise overview of various degradation modalities, their clinical applications, and potential future directions in the field of protein degradation., Introduction Small molecule-induced protein degradation is a rapidly developing mode of therapeutic activity in which ubiquitin ligases are redirected to induce selective degradation of target proteins. Several degraders were used [...]

Mitochondrial biogenesis and functions depend on the import of precursor proteins via the 'translocase of the outer membrane' (TOM complex). Defects in protein import lead to an accumulation of mitochondrial precursor proteins that induces a range of cellular stress responses. However, constitutive quality-control mechanisms that clear trapped precursor proteins from the TOM channel under non-stress conditions have remained unknown. Here we report that in Saccharomyces cerevisiae Ubx2, which functions in endoplasmic reticulum-associated degradation, is crucial for this quality-control process. A pool of Ubx2 binds to the TOM complex to recruit the AAA ATPase Cdc48 for removal of arrested precursor proteins from the TOM channel. This mitochondrial protein translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex under non-stress conditions to prevent clogging of the TOM channel with precursor proteins. The mitoTAD pathway ensures that mitochondria maintain their full protein-import capacity, and protects cells against proteotoxic stress induced by impaired transport of proteins into mitochondria. In Saccharomyces cerevisiae, Ubx2 promotes clearing trapped precursor proteins from the channel of the translocase of the outer membrane, in a translocation-associated degradation pathway that maintains the protein import capacity of mitochondria., Author(s): Christoph U. Mårtensson [sup.1] [sup.2] , Chantal Priesnitz [sup.1] [sup.2] , Jiyao Song [sup.1] , Lars Ellenrieder [sup.1] [sup.6] , Kim Nguyen Doan [sup.1] [sup.2] , Felix Boos [sup.3] [...]

Mathematical modelling and simulations reveal that including antibiotic degraders in ecological models of microbial species interaction allows the system to robustly move towards an intermixed stable state, more representative of real-world observations. Microbial community structure Understanding how stability in multispecies communities is maintained in the face of negative interactions via antibiotic production is a key goal in microbial ecology. Most ecological models for antibiotic interactions assume pairwise relationships between species that result in rock-scissor-paper type cycling and spatial separation. This doesn't reflect the in situ observations though, where communities are far more intermixed. Instead, Eric Kelsic and colleagues propose a three-species interaction assay, in which one species is capable of antibiotic degradation. Using a mixture of modelling and experimental validation, the authors show that including antibiotic degraders allows the system to robustly move towards an intermixed stable state. A major challenge in theoretical ecology is understanding how natural microbial communities support species diversity.sup.1,2,3,4,5,6,7,8, and in particular how antibiotic-producing, -sensitive and -resistant species coexist.sup.9,10,11,12,13,14,15. While cyclic 'rock-paper-scissors' interactions can stabilize communities in spatial environments.sup.9,10,11, coexistence in unstructured environments remains unexplained.sup.12,16. Here, using simulations and analytical models, we show that the opposing actions of antibiotic production and degradation enable coexistence even in well-mixed environments. Coexistence depends on three-way interactions in which an antibiotic-degrading species attenuates the inhibitory interactions between two other species. These interactions enable coexistence that is robust to substantial differences in inherent species growth rates and to invasion by 'cheating' species that cease to produce or degrade antibiotics. At least two antibiotics are required for stability, with greater numbers of antibiotics enabling more complex communities and diverse dynamic behaviours ranging from stable fixed points to limit cycles and chaos. Together, these results show how multi-species antibiotic interactions can generate ecological stability in both spatially structured and mixed microbial communities, suggesting strategies for engineering synthetic ecosystems and highlighting the importance of toxin production and degradation for microbial biodiversity., Author(s): Eric D. Kelsic [sup.1] , Jeffrey Zhao [sup.1] , Kalin Vetsigian [sup.2] , Roy Kishony [sup.1] [sup.3] Author Affiliations: (1) Department of Systems Biology, Harvard Medical School, Boston, USA [...]