BACKGROUND: A third of endovascularly treated patients with stroke experience incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3), and the natural evolution of this incomplete reperfusion remains unknown. We systematically reviewed the literature and performed a meta-analysis on the natural evolution of incomplete reperfusion after endovascular therapy. METHODS: A systematic review of MEDLINE, Embase, and PubMed up until March 1, 2024, using a predefined strategy. Only full-text English-written articles reporting rates of either favorable (ie, delayed reperfusion (DR) or no new infarct) or unfavorable progression (ie, persistent perfusion deficit or new infarct) of incompletely reperfused tissue were included. The primary outcome was the rate of DR and its association with functional independence (modified Rankin Scale score, 0-2) at 90 days postintervention. Pooled odds ratios with 95% CIs were calculated using a random-effects model. RESULTS: Six studies involving 950 patients (50.7% female; median age, 71 years; interquartile range, 60-79) were included. Four studies assessed the evolution of incomplete reperfusion on magnetic resonance imaging perfusion imaging, while 2 studies used diffusion-weighted imaging and noncontrast computed tomography imaging, where new infarct was used to denote unfavorable progression. Five studies defined incomplete reperfusion as eTICI 2b50 or 2c. DR occurred in 41% (interquartile range, 33%-51%) of cases 24 hours postintervention. Achieving DR was associated with a higher likelihood of functional independence at 90 days (odds ratio, 2.5 [95% CI, 1.9-3.4]). CONCLUSIONS: Nearly half of eTICI <3 patients achieve DR, leading to favorable clinical outcomes. This subgroup may derive limited or potentially harmful effects from pursuing additional reperfusion strategies (eg, intra-arterial lytics or secondary thrombectomy). Accurately predicting the evolution of incomplete reperfusion could optimize patient selection for adjunctive reperfusion strategies at the end of an intervention. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT05499832.

• MeSH
• Endovascular Procedures * methods   MeSH
• Ischemic Stroke * surgery   diagnostic imaging   therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Reperfusion methods   MeSH
• Aged MeSH
• Thrombolytic Therapy methods   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH

In this manuscript, we highlight the evolutionary origins of mitochondria from bacterial endosymbionts and explore their contributions to health, energy metabolism, and neural-immune communication. Mitochondrial adaptability and the roles played by these organelles in promoting oxygen-dependent ATP production provide critical regulation of cognition, motivation, and inflammation. Hypoxia has been identified as an important initiator of inflammation, neurodegeneration, and mitochondrial dysfunction, emphasizing the overall importance of oxygen homeostasis to health and well-being. The Behavior, Exercise, Relaxation, and Nutrition framework highlights these observations as tools that can be used to optimize mitochondrial efficiency. Interestingly, mitochondrial dysfunction may also be linked to psychiatric disorders (e.g., schizophrenia), a hypothesis that focuses on energy dynamics, a proposal that may extend our understanding of these disorders beyond traditional neurotransmitter-focused concepts. Collectively, these perspectives underscore the critical contributions of mitochondria to health and disease and offer a novel framework that may help to explain the connections featured in mind-body medicine.

• MeSH
• Biological Evolution MeSH
• Pain * metabolism   physiopathology   MeSH
• Exercise * physiology   MeSH
• Energy Metabolism * MeSH
• Cognition * physiology   MeSH
• Humans MeSH
• Mitochondria metabolism   MeSH
• Motivation * MeSH
• Pleasure * physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Across the tree of life, DNA damage response (DDR) proteins play a pivotal, yet dichotomous role in organismal development and evolution. Here, we present a comprehensive analysis of 432 DDR proteins encoded by 68 genomes, including that of Nucleospora cyclopteri, an intranuclear microsporidia sequenced in this study. We compared the DDR proteins encoded by these genomes to those of humans to uncover the DNA repair-ome across phylogenetically distant eukaryotes. We also performed further analyses to understand if organismal complexity and lifestyle play a role in the evolution of DDR protein length and conserved domain architecture. We observed that the genomes of extreme parasites such as Paramicrocytos, Giardia, Spironucleus, and certain microsporidian lineages encode the smallest eukaryotic repertoire of DDR proteins and that pathways involved in modulation of nucleotide pools and nucleotide excision repair are the most preserved DDR pathways in the eukaryotic genomes analysed here. We found that DDR and DNA repair proteins are consistently longer than housekeeping and metabolic proteins. This is likely due to the higher number of physical protein-protein interactions which DDR proteins are involved. We find that although DNA repair proteins are generally longer than housekeeping proteins, their functional domains occupy a relatively smaller footprint. Notably, this pattern holds true across diverse organisms and shows no dependence on either lifestyle or mitochondrial status. Finally, we observed that unicellular organisms harbour proteins that are tenfold longer than their human homologues, with the extra amino acids forming interdomain regions with a clearly novel albeit undetermined function.

• MeSH
• Eukaryota * genetics   MeSH
• Phylogeny MeSH
• Humans MeSH
• Microsporidia genetics   MeSH
• Evolution, Molecular * MeSH
• DNA Repair * MeSH
• DNA Damage * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Alpha-mannosidosis is a rare recessive lysosomal storage disorder with progressive multi-systemic impacts. In the absence of standardized monitoring protocols, there is insufficient understanding of disease progression over time. This study explored the evolution of the burden of illness and quality of life (QoL) experienced by patients with alpha-mannosidosis via an international patient and caregiver-based survey. The online survey was distributed to adult patients/caregivers of patients ≥ 10 years old. It included visual analogue scales (VAS; timepoints 5 years ago and now), multiple choice, and open text questions. We report a subset of functional and QoL data: walking ability, pain/discomfort, ability to self-care, and mental health. RESULTS: Analyses include 51 responses from 18 countries: 26 patients were on velmanase alfa enzyme replacement therapy (ERT), seven had been treated with hematopoietic stem cell transplantation (HSCT) and 18 were untreated patients (UP). Over 5 years, VAS scores showed the least decline in walking ability for HSCT patients (+ 0.1 ± 1.9) compared to patients receiving ERT (+ 0.7 ± 1.2) and UP (+ 1.8 ± 2.0). A trend towards improvement in pain was only observed for those on ERT (-0.2 ± 2.0), both for pediatric and adult patients. Ability to self-care improved for patients treated with HSCT (-1.0 ± 1.8) and slightly improved with ERT (-0.3 ± 1.5) but worsened for UP (+ 0.6 ± 0.9). Similarly, a trend towards improvement in mental health scores was observed for patients on ERT (-0.4 ± 2.2). CONCLUSIONS: Alpha-mannosidosis is associated with a substantial and progressive burden in UP, including deterioration in walking ability, pain, self-care and mental health. The survey results suggest that treatment with ERT or HSCT may slow this natural progression of alpha-mannosidosis, with these patients following a different disease trajectory to those solely receiving supportive care. This study could inform the natural pathway of alpha-mannosidosis to recognize patients' needs, courses of care, and the design of interventional studies.

• MeSH
• alpha-Mannosidosis * physiopathology   therapy   MeSH
• Pain * physiopathology   MeSH
• Adult MeSH
• Mental Health MeSH
• Enzyme Replacement Therapy MeSH
• Quality of Life MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Caregivers MeSH
• Self Care MeSH
• Surveys and Questionnaires MeSH
• Hematopoietic Stem Cell Transplantation MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Non-canonical (non-B) DNA structures-e.g. bent DNA, hairpins, G-quadruplexes (G4s), Z-DNA, etc.-which form at certain sequence motifs (e.g. A-phased repeats, inverted repeats, etc.), have emerged as important regulators of cellular processes and drivers of genome evolution. Yet, they have been understudied due to their repetitive nature and potentially inaccurate sequences generated with short-read technologies. Here we comprehensively characterize such motifs in the long-read telomere-to-telomere (T2T) genomes of human, bonobo, chimpanzee, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. Non-B DNA motifs are enriched at the genomic regions added to T2T assemblies and occupy 9%-15%, 9%-11%, and 12%-38% of autosomes and chromosomes X and Y, respectively. G4s and Z-DNA are enriched at promoters and enhancers, as well as at origins of replication. Repetitive sequences harbor more non-B DNA motifs than non-repetitive sequences, especially in the short arms of acrocentric chromosomes. Most centromeres and/or their flanking regions are enriched in at least one non-B DNA motif type, consistent with a potential role of non-B structures in determining centromeres. Our results highlight the uneven distribution of predicted non-B DNA structures across ape genomes and suggest their novel functions in previously inaccessible genomic regions.

• MeSH
• DNA * chemistry   genetics   MeSH
• G-Quadruplexes MeSH
• Genome, Human MeSH
• Genome * MeSH
• Hominidae * genetics   MeSH
• Humans MeSH
• Nucleotide Motifs MeSH
• Pan troglodytes genetics   MeSH
• Repetitive Sequences, Nucleic Acid MeSH
• Telomere * genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The disease currently known as frontotemporal dementia (FTD) has undergone a complex evolution from its first description by Arnold Pick and later by Alois Alzheimer, through the first clinicopathological criteria introduced by David Neary and David Mann, to its current nomenclatural perception as a complex clinicopathological entity. Currently, Frontotemporal lobar degeneration is viewed as a heterogeneous syndrome caused by progressive degeneration of the frontal and temporal lobes of the brain. Clinically, it can manifest as three syndromes of frontotemporal dementia (behavioral variant of FTD, progressive non-fluent aphasia and semantic dementia) but also as so-called "overlap" syndromes involving corticobasal degeneration and progressive supranuclear palsy. Its prevalence is about 10 % among all dementias and 40 % among dementias with onset between 45 and 65 years of age. The clinical manifestation of the different subtypes varies, the common denominator being behavioral disturbances and impairment of fatic, gnostic and executive functions. Mnestic and visuo-spatial functions, although preserved for a relatively long time, are superimposed by personality disintegration, fatic, gnostic and executive dysfunction. Compared with Alzheimer's disease, it generally has an earlier age of onset, a more rapid course and more devastating impairment of individual cognitive domains. FTD has a heritability of more than 30 % according to current knowledge. The main genes involved are MAPT, C9orf72 and GRN. More rarely affected genes are VCP, TDP-43, FUS and CHMP2B. In our article, we focus on the genetics of FTD and the clinic-genetic-pathological correlations. We also aim to provide a plastic picture of how individual mutations affect the molecular mechanisms of neurodegeneration.

• MeSH
• Epigenesis, Genetic genetics   MeSH
• Frontotemporal Dementia * diagnosis   genetics   classification   MeSH
• Genetic Testing methods   MeSH
• Humans MeSH
• Primary Progressive Nonfluent Aphasia diagnosis   genetics   MeSH
• Progranulins genetics   MeSH
• tau Proteins genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Diplonemids are among the most abundant and species-rich protists in the oceans. Marine heterotrophic flagellates, including diplonemids, have been suggested to play important roles in global biogeochemical cycles. Diplonemids are also the sister taxon of kinetoplastids, home to trypanosomatid parasites of global health importance, and thus are informative about the evolution of kinetoplastid biology. However, the genomic and cellular complement that underpins diplonemids' highly successful lifestyle is underexplored. At the same time, our framework describing cellular processes may not be as broadly applicable as presumed, as it is largely derived from animal and fungal model organisms, a small subset of extant eukaryotic diversity. In addition to uniquely evolved machinery in animals and fungi, there exist components with sporadic (i.e., "patchy") distributions across other eukaryotes. A most intriguing subset are components ("jötnarlogs") stochastically present in a wide range of eukaryotes but lost in animal and/or fungal models. Such components are considered exotic curiosities but may be relevant to inferences about the complexity of the last eukaryotic common ancestor (LECA) and frameworks of modern cell biology. Here, we use comparative genomics and phylogenetics to comprehensively assess the membrane-trafficking system of diplonemids. They possess several proteins thought of as kinetoplastid specific, as well as an extensive set of patchy proteins, including jötnarlogs. Diplonemids apparently function with endomembrane machinery distinct from existing cell biological models but comparable with other free-living heterotrophic protists, highlighting the importance of including such exotic components when considering different models of ancient eukaryotic genomic complexity and the cell biology of non-opisthokont organisms.

• MeSH
• Biological Evolution MeSH
• Phylogeny MeSH
• Kinetoplastida * physiology   genetics   MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: Muscle magnetic resonance imaging (MRI) is an emerging method in the diagnosis and monitoring of muscular dystrophies. This cross-sectional, comparative study aimed to evaluate quantitative MRI (qMRI) parameters of the lumbar paraspinal muscles (LPM) in myotonic dystrophy type 2 (DM2), to assess their relationship with functional examination, and to evaluate their evolution with aging. METHODS: The study enrolled 37 DM2 patients and 90 healthy volunteers (HV) who were matched based on physiological parameters to create 35 pairs. Utilizing a 6-point Dixon gradient echo sequence MRI, fat fraction (FF), total muscle volume, and functional muscle volume (FMV) of the LPM and psoas muscle (PS) were obtained. Using correlation coefficients and regression models, the relationship between MRI and the maximal isometric lumbar extensor muscle strength (MILEMS) and lumbar extensor muscle endurance (LEME), and their evolution with age, were assessed. RESULTS: LPM showed significantly higher FF in DM2 patients compared to HV (21.3% vs. 11.3%, p-value <0.001). FMV of LPM correlated significantly with MILEMS (ρ = 0.5, p- value = 0.001) and FF with LEME (ρ = -0.49, p- value = 0.002) in DM2. No significant differences in the rate of deterioration in functional and morphological parameters of the LPM with age were observed between the two groups. CONCLUSION: We demonstrated morphological correlates of lumbar extensor muscle dysfunction in DM2 patients. The qMRI parameters of LPM correlated with functional parameters but could not be used either as a reliable biomarker of lumbar extensor muscle impairment or as a biomarker of disease progression.

• Publication type
• Journal Article MeSH

An organism is considered "alive" if it can grow, reproduce, respond to external stimuli, metabolize nutrients, and maintain stability. By this definition, both mitochondria and viruses exhibit the key characteristics of independent life. In addition to their capacity for self-replication under specifically defined conditions, both mitochondria and viruses can communicate via shared biochemical elements, alter cellular energy metabolism, and adapt to their local environment. To explain this phenomenon, we hypothesize that early viral prototype species evolved from ubiquitous environmental DNA and gained the capacity for self-replication within coacervate-like liquid droplets. The high mutation rates experienced in this environment streamlined their acquisition of standard genetic codes and adaptation to a diverse set of host environments. Similarly, mitochondria, eukaryotic intracellular organelles that generate energy and resolve oxygen toxicity, originally evolved from an infectious bacterial species and maintain their capacity for active functionality within the extracellular space. Thus, while mitochondria contribute profoundly to eukaryotic cellular homeostasis, their capacity for freestanding existence may lead to functional disruptions over time, notably, the overproduction of reactive oxygen species, a phenomenon strongly linked to aging-related disorders. Overall, a more in-depth understanding of the full extent of the evolution of both viruses and mitochondria from primordial precursors may lead to novel insights and therapeutic strategies to address neurodegenerative processes and promote healthy aging.

• MeSH
• Energy Metabolism MeSH
• Humans MeSH
• Mitochondria * metabolism   MeSH
• Origin of Life * MeSH
• Viruses * metabolism   genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Mikroorganismy si během evoluce vyvinuly širokou škálu strategií, jak uniknout vrozenému i adaptivnímu imunitnímu systému, a některým těmto strategiím se věnujeme v našem přehledu. Mikroorganismy mohou využívat podobnost svých proteinů s proteiny hostitele, produkovat protizánětlivé faktory, narušovat komplementový systém, ovlivňovat funkci a blokovat syntézu cytokinů, inhibovat rozpoznávání imunoglobulinů, snižovat expresi a modifikovat antigeny na svém povrchu, narušovat zpracování a prezentaci antigenu imunitními buňkami, vstupovat do imunitních buněk, ovlivňovat apoptózu buněk, modulovat funkce imunitních buněk nebo ovlivňovat produkci hormonů. S těmito únikovými strategiemi je nutné počítat při léčbě infekčních onemocnění.

Microorganisms have evolved a wide variety of strategies to evade both the innate and adaptive immune systems during evolution, and some of these strategies are addressed in our review. Microorganisms can use the similarity of their proteins to host proteins, produce anti-inflammatory factors, disrupt the complement system, affect the function and block the synthesis of cytokines, inhibit the recognition of immunoglobulins, reduce the expression and modify antigens on their surface, disrupt the processing and presentation of antigen by immune cells, enter immune cells , influence cell apoptosis, modulate immune cell functions or influence hormone production. These escape strategies must be taken into account when treating infectious diseases.

• Keywords
• únikové strategie mikroorganismů,
• MeSH
• Host-Pathogen Interactions MeSH
• Humans MeSH
• Microbiological Phenomena * MeSH
• Immunity, Innate * MeSH
• Trained Immunity MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH