Communications Biology
2399-3642
Mỹ
Cơ quản chủ quản: Springer Nature , NATURE PORTFOLIO
Lĩnh vực:
Biochemistry, Genetics and Molecular Biology (miscellaneous)Agricultural and Biological Sciences (miscellaneous)Medicine (miscellaneous)
Phân tích ảnh hưởng
Thông tin về tạp chí
Communications Biology is an open access journal from Nature Research publishing high-quality research, reviews and commentary in all areas of the biological sciences. Research papers published by the journal represent significant advances bringing new biological insight to a specialized area of research. We also aim to provide a community forum for issues of importance to all biologists, regardless of sub-discipline.
Các bài báo tiêu biểu
Pharmacological systems analysis defines EIF4A3 functions in cell-cycle and RNA stress granule formation Abstract The RNA helicase EIF4A3 regulates the exon junction complex and nonsense-mediated mRNA decay functions in RNA transcript processing. However, a transcriptome-wide network definition of these functions has been lacking, in part due to the lack of suitable pharmacological inhibitors. Here we employ short-duration graded EIF4A3 inhibition using small molecule allosteric inhibitors to define the transcriptome-wide dependencies of EIF4A3. We thus define conserved cellular functions, such as cell cycle control, that are EIF4A3 dependent. We show that EIF4A3-dependent splicing reactions have a distinct genome-wide pattern of associated RNA-binding protein motifs. We also uncover an unanticipated role of EIF4A3 in the biology of RNA stress granules, which sequester and silence the translation of most mRNAs under stress conditions and are implicated in cell survival and tumour progression. We show that stress granule induction and maintenance is suppressed on the inhibition of EIF4A3, in part through EIF4A3-associated regulation of G3BP1 and TIA1 scaffold protein expression.
Tập 2 Số 1
pH-responsive high stability polymeric nanoparticles for targeted delivery of anticancer therapeutics Abstract The practical application of nanoparticles (NPs) as chemotherapeutic drug delivery systems is often hampered by issues such as poor circulation stability and targeting inefficiency. Here, we have utilized a simple approach to prepare biocompatible and biodegradable pH-responsive hybrid NPs that overcome these issues. The NPs consist of a drug-loaded polylactic-co-glycolic acid (PLGA) core covalently ‘wrapped’ with a crosslinked bovine serum albumin (BSA) shell designed to minimize interactions with serum proteins and macrophages that inhibit target recognition. The shell is functionalized with the acidity-triggered rational membrane (ATRAM) peptide to facilitate internalization specifically into cancer cells within the acidic tumor microenvironment. Following uptake, the unique intracellular conditions of cancer cells degrade the NPs, thereby releasing the chemotherapeutic cargo. The drug-loaded NPs showed potent anticancer activity in vitro and in vivo while exhibiting no toxicity to healthy tissue. Our results demonstrate that the ATRAM-BSA-PLGA NPs are a promising targeted cancer drug delivery platform.
Tập 3 Số 1
GardeninA confers neuroprotection against environmental toxin in a Drosophila model of Parkinson’s disease Abstract Parkinson’s disease is an age-associated neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons from the midbrain. Epidemiological studies have implicated exposures to environmental toxins like the herbicide paraquat as major contributors to Parkinson’s disease etiology in both mammalian and invertebrate models. We have employed a paraquat-induced Parkinson’s disease model in Drosophila as an inexpensive in vivo platform to screen therapeutics from natural products. We have identified the polymethoxyflavonoid, GardeninA, with neuroprotective potential against paraquat-induced parkinsonian symptoms involving reduced survival, mobility defects, and loss of dopaminergic neurons. GardeninA-mediated neuroprotection is not solely dependent on its antioxidant activities but also involves modulation of the neuroinflammatory and cellular death responses. Furthermore, we have successfully shown GardeninA bioavailability in the fly heads after oral administration using ultra-performance liquid chromatography and mass spectrometry. Our findings reveal a molecular mechanistic insight into GardeninA-mediated neuroprotection against environmental toxin-induced Parkinson’s disease pathogenesis for novel therapeutic intervention.
Tập 4 Số 1
Structural studies reveal flexible roof of active site responsible for ω-transaminase CrmG overcoming by-product inhibition Abstract Amine compounds biosynthesis using ω-transaminases has received considerable attention in the pharmaceutical industry. However, the application of ω-transaminases was hampered by the fundamental challenge of severe by-product inhibition. Here, we report that ω-transaminase CrmG from Actinoalloteichus cyanogriseus WH1-2216-6 is insensitive to inhibition from by-product α-ketoglutarate or pyruvate. Combined with structural and QM/MM studies, we establish the detailed catalytic mechanism for CrmG. Our structural and biochemical studies reveal that the roof of the active site in PMP-bound CrmG is flexible, which will facilitate the PMP or by-product to dissociate from PMP-bound CrmG. Our results also show that amino acceptor caerulomycin M (CRM M), but not α-ketoglutarate or pyruvate, can form strong interactions with the roof of the active site in PMP-bound CrmG. Based on our results, we propose that the flexible roof of the active site in PMP-bound CrmG may facilitate CrmG to overcome inhibition from the by-product.
Tập 3 Số 1
Z-DNA and Z-RNA in human disease Abstract Left-handed Z-DNA/Z-RNA is bound with high affinity by the Zα domain protein family that includes ADAR (a double-stranded RNA editing enzyme), ZBP1 and viral orthologs regulating innate immunity. Loss-of-function mutations in ADAR p150 allow persistent activation of the interferon system by Alu dsRNAs and are causal for Aicardi-Goutières Syndrome. Heterodimers of ADAR and DICER1 regulate the switch from RNA- to protein-centric immunity. Loss of DICER1 function produces age-related macular degeneration, a different type of Alu-mediated disease. The overlap of Z-forming sites with those for the signal recognition particle likely limits invasion of primate genomes by Alu retrotransposons.
Tập 2 Số 1
Coordination between binocular field and spontaneous self-motion specifies the efficiency of planarians’ photo-response orientation behavior Abstract Eyes show remarkable diversity in morphology among creatures. However, little is known about how morphological traits of eyes affect behaviors. Here, we investigate the mechanisms responsible for the establishment of efficient photo-response orientation behavior using the planarian Dugesia japonica as a model. Our behavioral assays reveal the functional angle of the visual field and show that the binocular field formed by paired eyes in D . japonica has an impact on the accurate recognition of the direction of a light source. Furthermore, we find that the binocular field in coordination with spontaneous wigwag self-motion of the head specifies the efficiency of photo-responsive evasive behavior in planarians. Our findings suggest that the linkage between the architecture of the sensory organs and spontaneous self-motion is a platform that serves for efficient and adaptive outcomes of planarian and potentially other animal behaviors.
Tập 1 Số 1