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Reimers, M.

Publications and source records attributed to Reimers, M..

8 recordsLinked to original sources

Functional specialization of the gibberellin receptor GIBBERELLIN-INSENSITIVE DWARF 1C in plant neighbour detection

Plants detect neighbours through a reduced red-to-far-red ratio (R:FR), triggering elongation growth that reduces crop yield. Although Gibberellin (GA) is required for the neighbour-proximity (NP) elongation response, bioactive GA levels do not increase sufficiently to account for elongation magnitude, suggesting GA sensitivity as an additional regulated variable. Here, we show that GID1C, one of three Arabidopsis GA receptors, is the primary GA receptor involved in NP-induced elongation. GID1C protein accumulates selectively in hypocotyls and root tips under low R:FR without an increase in bioactive GA. The gid1c mutant shows a reduced elongation response that exogenous GA treatment cannot rescue. Transcriptome profiling reveals that GID1C controls 86% of the NP-responsive transcriptome, including genes for cell growth, division, and transcriptional regulation. Hub analysis identifies ICE1 as a GID1C-repressed transcriptional brake. ICE1 transcript is suppressed under low R:FR in a GID1C-dependent manner, and a phosphorylation-resistant ICE1 allele blocks NP-induced elongation. Together, these findings establish GA perception as an additional regulatory layer in NP, with subfunctionalisation among GID1 paralogs shaping the response to neighbouring plants.

plant biology↗

A systematic analysis of brain tissue response to microelectrode material and size with single-cell spatial transcriptomics

Implantable microelectrode arrays can interface with the central nervous system to record from and/or stimulate neural tissues to treat neurological disease and injury. The chronic tissue response to implanted electrodes is believed to be a driving factor behind microelectrode failure. Next-generation electrodes have been developed to attenuate the tissue response by reducing electrode size and/or incorporating softer materials. In this study, we used single-cell-resolution spatial transcriptomics to quantify the tissue response to implanted electrodes within custom-classified cell types in the rat brain. To test the effects of implant material and size, we assessed polyimide and silicon electrodes of 10 {micro}m and 100 {micro}m cross-sectional dimensions over 6-weeks post-implantation. Our data indicate that implants are associated with upregulation of inflammatory genes in glia that are coupled to damage-initiated losses in synaptic transmission and subsequent engagement of compensatory protective mechanisms (e.g., re-myelination, antioxidant production) to preserve local neurons. While bulk tissue analysis reinforced previously reported observations of glial scar consolidation over time, single cell analysis revealed an unexpected, progressive heightening of the expression of inflammatory genes in individual device-reactive astrocytes. With respect to design features, the impact of device dimensions more heavily influenced responses than material type, particularly by the 6-week time point. Our results add single-cell resolution observations to the growing use of transcriptomics to understand the biocompatibility of devices implanted in the brain.

neuroscience↗

The trimeric thylakoidal Tat receptor complex consists of a homo-oligomeric TatC core with associated TatB subunits

The Twin-arginine translocation (Tat) machinery, which is found in most cellular membranes containing a respiratory or photosynthetic electron transport chain, is characterized by its unique ability to catalyze membrane transport of folded proteins without impairing the membrane potential. In plant thylakoids, Tat machinery consists of three subunits, TatA, TatB, and TatC, with the latter two, TatB and TatC, forming membrane-integral multimeric TatBC receptor complexes. Here we have analyzed the stability and the subunit composition of these complexes after solubilization of thylakoids with the mild detergent digitonin as well as after additional affinity-purification. Employing different detergent combinations and/or heat treatment (40{degrees}C) followed by BN-PAGE and Western analysis we could identify four distinct Tat complexes with apparent molecular masses ranging from approximately 230 kDa to 620 kDa. Treatment of the largest Tat complex with either heat or detergents like DDM or Triton X-114 led to its stepwise breakdown into the three smaller complexes resulting from the successive release of TatB subunits from a relatively stable TatC core complex. From these data we conclude that the fully assembled, physiologically active TatBC receptor complex consists of a stable, trimeric TatC core to which three TatB subunits are bound independently from each other.

cell biology↗

A conserved microtubule-binding region in Xanthomonas XopL is indispensable for induced plant cell death reactions.

Pathogenic Xanthomonas bacteria cause disease on more than 400 plant species. These Gram-negative bacteria utilize the type III secretion system to inject type III effector proteins (T3Es) directly into the plant cell cytosol where they can manipulate plant pathways to promote virulence. The host range of a given Xanthomonas species is limited, and T3E repertoires are specialized during interactions with specific plant species. Some effectors, however, are retained across most strains, such as Xanthomonas Outer Protein L (XopL). As an ancestral effector, XopL contributes to the virulence of multiple xanthomonads, infecting diverse plant species. XopL homologs harbor a combination of a leucine-rich-repeat (LRR) domain and an XL-box which has E3 ligase activity. Despite similar domain structure there is evidence to suggest that XopL function has diverged, exemplified by the finding that XopLs expressed in plants often display bacterial species-dependent differences in their sub-cellular localization and plant cell death reactions. We found that XopL from X. euvesicatoria (XopLXe) directly associates with plant microtubules (MTs) and causes strong cell death in agroinfection assays in N. benthamiana. Localization of XopLXe homologs from three additional Xanthomonas species, of diverse infection strategy and plant host, revealed that only the distantly related X. campestris pv. campestris harbors a XopL (XopLXcc) that fails to localize to MTs and to cause plant cell death. Comparative sequence analyses of MT-binding XopLs and XopLXcc identified a proline-rich-region (PRR)/-helical region important for MT localization. Functional analyses of XopLXe truncations and amino acid exchanges within the PRR suggest that MT-localized XopL activity is required for plant cell death reactions. This study exemplifies how the study of a T3E within the context of a genus rather than a single species can shed light on how effector localization is linked to biochemical activity. Author summaryXanthomonas Outer Proteins (Xops) are type III effector proteins originating from bacterial plant pathogens of the Xanthomonas genus. Xanthomonas uses a needle-like structure to inject a cocktail of Xops directly into plant cells where they manipulate cellular processes to promote virulence. Previous studies of individual Xops have provided valuable insights into virulence strategies used by Xanthomonas, knowledge that can be exploited to fight plant disease. However, despite rapid progress in the field, there is much about effector activity we still do not understand. Our study focuses on the effector XopL, a protein with E3 ligase activity that is important for Xanthomonas virulence. In this study we expressed XopLs in leaves of the model plant N. benthamiana and found that XopLs from different Xanthomonas species differ in their subcellular localization. XopLs from closely related species associate with the microtubule cytoskeleton and disassemble it, whereas a XopL from a distantly related species did not. This prompted a comparative analysis of these proteins, which showed how microtubule binding is achieved and how it affects the plant response to XopL.

pathology↗

Head and Neck Cancer-derived small extracellular vesicles sensitize TRPV1+ neurons to mediate cancer pain

Severe pain is often experienced by patients with head and neck cancer and is associated with a poor prognosis. Despite its frequency and severity, current treatments fail to adequately control cancer-associated pain, because of our lack of mechanistic understanding. Cancer-derived small extracellular vesicles (Cancer-sEVs) are well- positioned to function as mediators of communication between cancer cells and neurons. Inhibition of Cancer-sEV release attenuated pain in tumor-bearing mice. Injection of purified Cancer-sEVs is sufficient to induce pain hypersensitivity in naive mice. Cancer-sEVs triggered calcium influx in nociceptors and inhibition or ablation of nociceptors protect against cancer pain. Interrogation of published sequencing data of human sensory neurons exposed to human Cancer-sEVs suggested a stimulation of protein translation in neurons. Induction of translation by Cancer-sEVs was validated in our mouse model and its inhibition alleviated cancer pain in mice. These findings define a role of Cancer-sEVs in cancer pain and identify several druggable targets. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/506411v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@2a13a2org.highwire.dtl.DTLVardef@6f305dorg.highwire.dtl.DTLVardef@1d0417corg.highwire.dtl.DTLVardef@17b36df_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Functional classes of SNPs related to psychiatric disorders and behavioral traits contrast with those related to neurological disorders

We investigated the functional classes of genomic regions containing SNPS contributing most to the SNP-heritability of important psychiatric and neurological disorders and behavioral traits, as determined from recent genome-wide association studies. We employed linkage-disequilibrium score regression with several brain-specific genomic annotations not previously used. The classes of genomic annotations conferring substantial SNP-heritability for the psychiatric disorders and behavioral traits differed systematically from the classes associated with neurological disorders, and both differed from the classes enriched for height, a biometric trait used here as a control outgroup. The SNPs implicated in these psychiatric disorders and behavioral traits were highly enriched in CTCF binding sites, in conserved regions likely to be enhancers, and in brain-specific promoters, regulatory sites likely to affect dynamic responses. The SNPs relevant for neurological disorders were highly enriched in constitutive coding regions and splice regulatory sites. We suggest that our results provide a bridge between genetics and the well-known effects of life history and recent stressful experiences on risk of psychiatric illness.

genetics↗

Swimming direction of the Glass Catfish, Kryptopterus bicirrhis, is responsive to magnetic stimulation

Several marine species have developed a magnetic perception that is essential for navigation and detection of prey and predators. One of these species is the transparent glass catfish that contains an ampullary organ dedicated to sense magnetic fields. Here we examine the behavior of the glass catfish in response to static magnetic fields which will provide valuable insight on function of this magnetic response. By utilizing state of the art animal tracking software and artificial intelligence approaches, we quantified the effects of magnetic fields on the swimming direction of glass catfish. The results demonstrate that glass catfish placed in a radial arm maze, consistently swim away from magnetic fields over 20 {micro}T and show adaptability to changing magnetic field direction and location.

animal behavior and cognition↗

Separation of hemodynamic signals from GCaMP fluorescence measured with widefield imaging

Widefield calcium imaging is often used to measure brain dynamics in behaving mice. With a large field of view and a high sampling rate, widefield imaging can monitor activity from several distant cortical areas simultaneously, revealing cortical interactions. Interpretation of widefield images is complicated, however, by the absorption of light by hemoglobin, which can substantially affect the measured fluorescence. One approach to separating hemodynamics and calcium signals is to use multi-wavelength backscatter recordings to measure light absorption by hemoglobin. Following this approach, we develop a spatially-detailed regression-based method to estimate hemodynamics. The spatially-detailed model is based on a linear form of the Beer-Lambert relationship, but is fit at every pixel in the image and does not rely on the estimation of physical parameters. In awake mice of three transgenic lines, the Spatial Model offers improved separation of hemodynamics and changes in GCaMP fluorescence. The improvement is pronounced near blood vessels and, in contrast with other models based on regression or the Beer-Lambert law, can remove vascular artifacts along the sagittal midline. Compared to other separation approaches, the spatially-detailed model permits more accurate fluorescence-based determination of neuronal activity across the cortex.\n\nNEW & NOTEWORTHYThis manuscript addresses a well-known and strong source of contamination in widefield calcium imaging data: hemodynamics. To guide researchers towards the best method to separate calcium signals from hemodynamics, we compare the performance of several commonly used methods in three commonly-used Cre-driver lines, and we present a novel regression model that out-performs the other techniques we consider.

neuroscience↗