Immunosuppressive mechanisms of human bone marrow derived mesenchymal stromal cells in BALB/c host graft versus host disease murine models

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Nuclear Outsourcing of RNA Interference Components to Human Mitochondria

MicroRNAs (miRNAs) are small non-coding RNAs that associate with Argonaute proteins to regulate gene expression at the post-transcriptional level in the cytoplasm. However, recent studies have reported that some miRNAs localize to and function in other cellular compartments. Mitochondria harbour their own genetic system that may be a potential site for miRNA mediated post-transcriptional regulation. We aimed at investigating whether nuclear-encoded miRNAs can localize to and function in human mitochondria. To enable identification of mitochondrial-enriched miRNAs, we profiled the mitochondrial and cytosolic RNA fractions from the same HeLa cells by miRNA microarray analysis. Mitochondria were purified using a combination of cell fractionation and immunoisolation, and assessed for the lack of protein and RNA contaminants. We found 57 miRNAs differentially expressed in HeLa mitochondria and cytosol. Of these 57, a signature of 13 nuclear-encoded miRNAs was reproducibly enriched in mitochondrial RNA and validated by RT-PCR for hsa-miR-494, hsa-miR-1275 and hsa-miR-1974. The significance of their mitochondrial localization was investigated by characterizing their genomic context, cross-species conservation and instrinsic features such as their size and thermodynamic parameters. Interestingly, the specificities of mitochondrial versus cytosolic miRNAs were underlined by significantly different structural and thermodynamic parameters. Computational targeting analysis of most mitochondrial miRNAs revealed not only nuclear but also mitochondrial-encoded targets. The functional relevance of miRNAs in mitochondria was supported by the finding of Argonaute 2 localization to mitochondria revealed by immunoblotting and confocal microscopy, and further validated by the co-immunoprecipitation of the mitochondrial transcript COX3. This study provides the first comprehensive view of the localization of RNA interference components to the mitochondria. Our data outline the molecular bases for a novel layer of crosstalk between nucleus and mitochondria through a specific subset of human miRNAs that we termed ‘mitomiRs’

Comparing unilateral and bilateral upper limb training: The ULTRA-stroke program design

<p>Abstract</p> <p>Background</p> <p>About 80% of all stroke survivors have an upper limb paresis immediately after stroke, only about a third of whom (30 to 40%) regain some dexterity within six months following conventional treatment programs. Of late, however, two recently developed interventions - constraint-induced movement therapy (CIMT) and bilateral arm training with rhythmic auditory cueing (BATRAC) - have shown promising results in the treatment of upper limb paresis in chronic stroke patients. The ULTRA-stroke (acronym for Upper Limb TRaining After stroke) program was conceived to assess the effectiveness of these interventions in subacute stroke patients and to examine how the observed changes in sensori-motor functioning relate to changes in stroke recovery mechanisms associated with peripheral stiffness, interlimb interactions, and cortical inter- and intrahemispheric networks. The present paper describes the design of this single-blinded randomized clinical trial (RCT), which has recently started and will take several years to complete.</p> <p>Methods/Design</p> <p>Sixty patients with a first ever stroke will be recruited. Patients will be stratified in terms of their remaining motor ability at the distal part of the arm (i.e., wrist and finger movements) and randomized over three intervention groups receiving modified CIMT, modified BATRAC, or an equally intensive (i.e., dose-matched) conventional treatment program for 6 weeks. Primary outcome variable is the score on the Action Research Arm test (ARAT), which will be assessed before, directly after, and 6 weeks after the intervention. During those test sessions all patients will also undergo measurements aimed at investigating the associated recovery mechanisms using haptic robots and magneto-encephalography (MEG).</p> <p>Discussion</p> <p>ULTRA-stroke is a 3-year translational research program which aims (1) to assess the relative effectiveness of the three interventions, on a group level but also as a function of patient characteristics, and (2) to delineate the functional and neurophysiological changes that are induced by those interventions.</p> <p>The outcome on the ARAT together with information about changes in the associated mechanisms will provide a better understanding of how specific therapies influence neurobiological changes, and which post-stroke conditions lend themselves to specific treatments.</p> <p>Trial Registration</p> <p>The ULTRA-stroke program is registered at the Netherlands Trial Register (NTR, <url>http://www.trialregister.nl</url>, number NTR1665).</p

The 2024 Outline of Fungi and fungus-like taxa

With the simultaneous growth in interest from the mycological community to discover fungal species and classify them, there is also an important need to assemble all taxonomic information onto common platforms. Fungal classification is facing a rapidly evolving landscape and organizing genera into an appropriate taxonomic hierarchy is central to better structure a unified classification scheme and avoid incorrect taxonomic inferences. With this in mind, the Outlines of Fungi and fungus-like taxa (2020, 2022) were published as an open-source taxonomic scheme to assist mycologists to better understand the taxonomic position of species within the Fungal Kingdom as well as to improve the accuracy and consistency of our taxonomic language. In this paper, the third contribution to the series of Outline of Fungi and fungus-like taxa prepared by the Global Consortium for the Classification of Fungi and fungus-like taxa is published. The former is updated considering our previous reviews and the taxonomic changes based on recent taxonomic work. In addition, it is more comprehensive and derives more input and consensus from a larger number of mycologists worldwide. Apart from listing the position of a particular genus in a taxonomic level, nearly 1000 notes are provided for newly established genera and higher taxa introduced since 2022. The notes section emphasizes on recent findings with corresponding references, discusses background information to support the current taxonomic status and some controversial taxonomic issues are also highlighted. To elicit maximum taxonomic information, notes/taxa are linked to recognized databases such as Index Fungorum, Faces of Fungi, MycoBank and GenBank, Species Fungorum and others. A new feature includes links to Fungalpedia, offering notes in the Compendium of Fungi and fungus-like Organisms. When specific notes are not provided, links are available to webpages and relevant publications for genera or higher taxa to ease data accessibility. Following the recent synonymization of Caulochytriomycota under Chytridiomycota, with Caulochytriomycetes now classified as a class within the latter, based on formally described and currently accepted data, the Fungi comprises 19 Phyla, 83 classes, 1,220 families, 10,685 genera and ca 140,000 species. Of the genera, 39.5% are monotypic and this begs the question whether mycologists split genera unnecessarily or are we going to find other species in these genera as more parts of the world are surveyed? They are 433 speciose genera with more than 50 species. The document also highlights discussion of some important topics including number of genera categorized as incertae sedis status in higher level fungal classification. The number of species at the higher taxonomic level has always been a contentious issue especially when mycologists consider either a lumping or a splitting approach and herein we provide figures. Herein a summary of updates in the outline of Basidiomycota is provided with discussion on whether there are too many genera of Boletales, Ceratobasidiaceae, and speciose genera such as Colletotrichum. Specific case studies deal with Cortinarius, early diverging fungi, Glomeromycota, a diverse early divergent lineage of symbiotic fungi, Eurotiomycetes, marine fungi, Myxomycetes, Phyllosticta, Hymenochaetaceae and Polyporaceae and the longstanding practice of misapplying intercontinental conspecificity. The outline will aid to better stabilize fungal taxonomy and serves as a necessary tool for mycologists and other scientists interested in the classification of the Fungi

ICAR: endoscopic skull‐base surgery

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