Ribosome Rescue and Translation Termination at Non-Standard Stop Codons by ICT1 in Mammalian Mitochondria

Release factors (RFs) govern the termination phase of protein synthesis. Human mitochondria harbor four different members of the class 1 RF family: RF1Lmt/mtRF1a, RF1mt, C12orf65 and ICT1. The homolog of the essential ICT1 factor is widely distributed in bacteria and organelles and has the peculiar feature in human mitochondria to be part of the ribosome as a ribosomal protein of the large subunit. The factor has been suggested to rescue stalled ribosomes in a codon-independent manner. The mechanism of action of this factor was obscure and is addressed here. Using a homologous mitochondria system of purified components, we demonstrate that the integrated ICT1 has no rescue activity. Rather, purified ICT1 binds stoichiometrically to mitochondrial ribosomes in addition to the integrated copy and functions as a general rescue factor, i.e. it releases the polypeptide from the peptidyl tRNA from ribosomes stalled at the end or in the middle of an mRNA or even from non-programmed ribosomes. The data suggest that the unusual termination at a sense codon (AGA/G) of the oxidative-phosphorylation enzymes CO1 and ND6 is also performed by ICT1 challenging a previous model, according to which RF1Lmt/mtRF1a is responsible for the translation termination at non-standard stop codons. We also demonstrate by mutational analyses that the unique insertion sequence present in the N-terminal domain of ICT1 is essential for peptide release rather than for ribosome binding. The function of RF1mt, another member of the class1 RFs in mammalian mitochondria, was also examined and is discussed

Neuroprotective DAMPs member prothymosin alpha has additional beneficial actions against cerebral ischemia-induced vascular damages

AbstractProthymosin alpha (ProTα) suppresses stress-induced necrosis of cultured cortical neurons. As neuroprotection alone could not explain the long-lasting protective actions against cerebral ischemia by ProTα, we further examined whether ProTα, in addition to neuroprotective effects, has other anti-ischemic activities. When recombinant mouse ProTα (rmProTα) at 0.3 mg/kg was intravenously (i.v.) given 2 h after the start of tMCAO, all mice survived for more than 14 days. In evaluation of CD31- and tomato lectin-labeling as well as IgG and Evans blue leakage, rmProTα treatment (0.1 mg/kg) largely blocked ischemia-induced vascular damages. Therefore, rmProTα has novel beneficial effects against ischemia-induced brain damage through vascular mechanisms

Disentangling the pedogenic factors controlling active Al and Fe concentrations in soils of the Cameroon volcanic line

Active Al, Fe and Si (i.e., oxalate extractable fraction: Alo, Feo, Sio) strongly affect soil physical, chemical and biological properties. This study examined the pedogenic factors affecting Alo, Feo and Sio contents across a soil weathering sequence in the Cameroon volcanic line. We investigated the B horizon (∼50-cm depth) from 26 soils formed in basaltic materials at different elevations (110–2570 m) incorporating a wide range of temperature (14–27 °C) and precipitation (1520–3130 mm). The weathering sequence ranged from weakly weathered Andisols in the southwest region grading to strongly weathered Oxisols on the central highlands. We assumed pyrophosphate extractable Al/Fe (Alp/Fep) as organo-Al/Fe complexes, and Sio, (Alo − Alp) and (Feo − Fep) as short-range-order (SRO) minerals. Factor analysis of climatic (e.g., temperature and precipitation/leaching metrics) and soil geochemical properties (e.g., weathering indices) identified three independent factors representing temperature/dry season intensity, weathering degree and precipitation/leaching as the primary determinants of Alo, Feo and Sio concentrations. Organo-metal complexes (Alp and Fep) were negatively correlated with the temperature/dry season intensity factor, whereas the SRO mineral phases (Sio, Alo − Alp and Feo − Fep) were negatively correlated with weathering degree. The precipitation/leaching factor positively correlated with Alo, Feo and Sio. Our analysis infers that low temperature promotes the formation and preservation of organo-Al/Fe complexes, whereas weathering degree is more critical for SRO minerals. Further, increased weathering and a drier climate enhance the formation of crystalline clay minerals at the expense of SRO minerals. Allophanic materials (Sio) were evident (Sio: 9–43 g kg⁻¹) only in weakly weathered soils. However, low allophanic contents were found in more highly weathered soils (Sio: 2–7 g kg⁻¹) accompanied by high Alp and Fep, suggesting the importance of volcanic parent materials as a direct source of Al and Fe via weathering for the formation of organo-metal complexes. In sum, we clarified the discriminatory effects of climatic factors and degree of weathering in regulating the composition of the active Al, Fe and Si fractions along the Cameroon volcanic line

Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.

The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP

Disentangling the pedogenic factors controlling active Al and Fe concentrations in soils of the Cameroon volcanic line

Active Al, Fe and Si (i.e., oxalate extractable fraction: Alo, Feo, Sio) strongly affect soil physical, chemical and biological properties. This study examined the pedogenic factors affecting Alo, Feo and Sio contents across a soil weathering sequence in the Cameroon volcanic line. We investigated the B horizon (∼50-cm depth) from 26 soils formed in basaltic materials at different elevations (110–2570 m) incorporating a wide range of temperature (14–27 °C) and precipitation (1520–3130 mm). The weathering sequence ranged from weakly weathered Andisols in the southwest region grading to strongly weathered Oxisols on the central highlands. We assumed pyrophosphate extractable Al/Fe (Alp/Fep) as organo-Al/Fe complexes, and Sio, (Alo − Alp) and (Feo − Fep) as short-range-order (SRO) minerals. Factor analysis of climatic (e.g., temperature and precipitation/leaching metrics) and soil geochemical properties (e.g., weathering indices) identified three independent factors representing temperature/dry season intensity, weathering degree and precipitation/leaching as the primary determinants of Alo, Feo and Sio concentrations. Organo-metal complexes (Alp and Fep) were negatively correlated with the temperature/dry season intensity factor, whereas the SRO mineral phases (Sio, Alo − Alp and Feo − Fep) were negatively correlated with weathering degree. The precipitation/leaching factor positively correlated with Alo, Feo and Sio. Our analysis infers that low temperature promotes the formation and preservation of organo-Al/Fe complexes, whereas weathering degree is more critical for SRO minerals. Further, increased weathering and a drier climate enhance the formation of crystalline clay minerals at the expense of SRO minerals. Allophanic materials (Sio) were evident (Sio: 9–43 g kg−1) only in weakly weathered soils. However, low allophanic contents were found in more highly weathered soils (Sio: 2–7 g kg−1) accompanied by high Alp and Fep, suggesting the importance of volcanic parent materials as a direct source of Al and Fe via weathering for the formation of organo-metal complexes. In sum, we clarified the discriminatory effects of climatic factors and degree of weathering in regulating the composition of the active Al, Fe and Si fractions along the Cameroon volcanic line

Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia

Abnormalities in the peripheral immune system are involved in the pathophysiology of fibromyalgia, although their contribution to the painful symptoms remains unknown. Our previous study reported the ability of splenocytes to develop pain-like behavior and an association between the central nervous system (CNS) and splenocytes. Since the spleen is directly innervated by sympathetic nerves, this study aimed to examine whether adrenergic receptors are necessary for pain development or maintenance using an acid saline-induced generalized pain (AcGP) model (an experimental model of fibromyalgia) and whether the activation of these receptors is also essential for pain reproduction by the adoptive transfer of AcGP splenocytes. The administration of selective β2-blockers, including one with only peripheral action, prevented the development but did not reverse the maintenance of pain-like behavior in acid saline-treated C57BL/6J mice. Neither a selective α1-blocker nor an anticholinergic drug affects the development of pain-like behavior. Furthermore, β2-blockade in donor AcGP mice eliminated pain reproduction in recipient mice injected with AcGP splenocytes. These results suggest that peripheral β2-adrenergic receptors play an important role in the efferent pathway from the CNS to splenocytes in pain development

Ecto-F0/F1 ATPase as a novel candidate of prothymosin α receptor

Objectives: Prothymosin α (ProTα) was reported to inhibit the neuronal necrosis by facilitating the plasma membrane localization of endocytosed glucose transporter 1/4 through an activation of putative Gi-coupled receptor. The present study aims to identify a novel ProTα target, which may lead to an activation of Gi-coupled receptor. Methods: We used Gi-rich lipid rafts fraction of retinal cell line N18-RE-105 cells for affinity cross-linking. The biological confirmation that F0/F1 ATPase is a target protein complex was performed by cell-free experiments using ELISA-based binding assay, surface plasmon resonance assay and quartz crystal microbalance assay, and cell-based experiments to measure extracellular ATP level in the HUVECs culture. Results: From the cross-linking study and above-mentioned protein-protein interaction assays, ATP5A1 and ATP5B, F1 ATPase subunits were found to ProTα binding target proteins. In the culture of HUVEC cells, furthermore, ProTα increased the extracellular ATP levels in a reversible manner by anti-ATP5A1- and ATP5B-antibodies. Conclusion: The present study suggests that ProTα may activate ecto-F0/F1 ATPase and produced ATP. This study leads to next subjects whether produced ATP and its metabolites, ADP or adenosine may activate corresponding Gi-coupled receptors

Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia

Abnormalities in the peripheral immune system are involved in the pathophysiology of fibromyalgia, although their contribution to the painful symptoms remains unknown. Our previous study reported the ability of splenocytes to develop pain-like behavior and an association between the central nervous system (CNS) and splenocytes. Since the spleen is directly innervated by sympathetic nerves, this study aimed to examine whether adrenergic receptors are necessary for pain development or maintenance using an acid saline-induced generalized pain (AcGP) model (an experimental model of fibromyalgia) and whether the activation of these receptors is also essential for pain reproduction by the adoptive transfer of AcGP splenocytes. The administration of selective β2-blockers, including one with only peripheral action, prevented the development but did not reverse the maintenance of pain-like behavior in acid saline-treated C57BL/6J mice. Neither a selective α1-blocker nor an anticholinergic drug affects the development of pain-like behavior. Furthermore, β2-blockade in donor AcGP mice eliminated pain reproduction in recipient mice injected with AcGP splenocytes. These results suggest that peripheral β2-adrenergic receptors play an important role in the efferent pathway from the CNS to splenocytes in pain development