Prototaxites reinterpreted as mega-rhizomorphs, facilitating nutrient transport in early terrestrial ecosystems.

The enigmatic fossil Prototaxites found in successions ranging from the Middle Ordovician to the Upper Devonian was originally described as having conifer affinity. The current debate, however, suggests that they probably represent gigantic algal-fungal symbioses. Our re-investigation of permineralized Prototaxites specimens from two localities, the Heider quarry in Germany and the Bordeaux quarry in Canada, reveals striking anatomical similarities with modern fungal rhizomorphs Armillaria mellea. We analysed extant fungal rhizomorphs and fossil Prototaxites through light microscopy of their anatomy, Fourier transform infrared spectroscopy, X-ray microscopy, and Raman spectroscopy. Based on these comparisons, we interpret the Prototaxites as fungi. The detailed preservation of cell walls and possible organelles seen in transverse sections of Prototaxites reveal that fossilization initiated while the organism was alive, inhibiting the collapse of delicate cellular structures. Prototaxites has been interpreted to grow vertically by many previous workers. Here we propose an alternative view that Prototaxites represents a complex hyphal aggregation (rhizomorph) that may have grown horizontally similar to modern complex aggregated mycelial growth forms, such as cords and rhizomorphs. Their main function was possibly to redistribute water and nutrition from nutrient-rich to nutrient-poor areas facilitating the expansion for early land plant communities.

Structural validity and internal consistency of the Strengths and Stressors in Parenting (SSF) Questionnaire in parents of children with developmental disabilities.

The current study investigated the structural validity and internal consistency of the Strengths and Stressors (SSF) questionnaire. The SSF is used in Swedish habilitation services to measure the positive and negative consequences that the fostering of a child with a developmental disability can have on family functioning in six domains: parent's feelings and attitudes, social life, family finances, relationship to the other parent, siblings, and professional support. The proposed six-factor model was tested with confirmatory factor analysis with data collected from 291 parents of children with developmental disabilities. The six-factor model had an acceptable fit according to most fit indices, but two items were non-significant. Overall, the internal consistency was acceptable or good. The SSF, with the proposed six-factor solution, can be a useful tool when assessing parental perspectives on the impacts of having a child with a developmental disability in clinical settings and research.

A Cryptic Alternative for the Evolution of Hyphae.

A growing awareness of a subsurface fossil record of mostly hyphal fungi organisms stretching back through the Phanerozoic to ≈400 megaannum (Ma) and possibly earlier, provides an alternative view on hyphal development. Parallel with the emergence of hyphal fungi during Ordovician-Devonian times when plants colonized the land, which is the traditional notion of hyphal evolution, hyphae-based fungi existed in the deep biosphere. New insights suggest that the fundamental functions of hyphae may have evolved in response to an ancient subsurface endolithic life style and might have been in place before the colonization of land. To address the gaps in the current understanding of hyphal evolution a strategy based on research prospects involving investigations of uncharted geological material, new diagnostics, and comparisons to live species is proposed.

A New Frontier for Palaeobiology: Earth's Vast Deep Biosphere.

Diverse micro-organisms populate a global deep biosphere hosted by rocks and sediments beneath land and sea, containing more biomass than any other biome except forests. This paper reviews an emerging palaeobiological archive of these dark habitats: microfossils preserved in ancient pores and fractures in the crust. This archive, seemingly dominated by mineralized filaments (although rods and coccoids are also reported), is presently far too sparsely sampled and poorly understood to reveal trends in the abundance, distribution, or diversity of deep life through time. New research is called for to establish the nature and extent of the fossil record of Earth's deep biosphere by combining systematic exploration, rigorous microanalysis, and experimental studies of both microbial preservation and the formation of abiotic pseudofossils within the crust. It is concluded that the fossil record of Earth's largest microbial habitat may still have much to tell us about the history of life, the evolution of biogeochemical cycles, and the search for life on Mars.

Fungi in Deep Subsurface Environments.

The igneous crust of the oceans and the continents represents the major part of Earth's lithosphere and has recently been recognized as a substantial, yet underexplored, microbial habitat. While prokaryotes have been the focus of most investigations, microeukaryotes have been surprisingly neglected. However, recent work acknowledges eukaryotes, and in particular fungi, as common inhabitants of the deep biosphere, including the deep igneous provinces. The fossil record of the subseafloor igneous crust, and to some extent the continental bedrock, establishes fungi or fungus-like organisms as inhabitants of deep rock since at least the Paleoproterozoic, which challenges the present notion of early fungal evolution. Additionally, deep fungi have been shown to play an important ecological role engaging in symbiosis-like relationships with prokaryotes, decomposing organic matter, and being responsible for mineral weathering and formation, thus mediating mobilization of biogeochemically important elements. In this review, we aim at covering the abundance and diversity of fungi in the various igneous rock provinces on Earth as well as describing the ecological impact of deep fungi. We further discuss what consequences recent findings might have for the understanding of the fungal distribution in extensive anoxic environments and for early fungal evolution.

Microbial Community Structure in a Serpentine-Hosted Abiotic Gas Seepage at the Chimaera Ophiolite, Turkey.

The surface waters at the ultramafic ophiolitic outcrop in Chimaera, Turkey, are characterized by high pH values and high metal levels due to the percolation of fluids through areas of active serpentinization. We describe the influence of the liquid chemistry, mineralogy, and H2 and CH4 levels on the bacterial community structure in a semidry, exposed, ultramafic environment. The bacterial and archaeal community structures were monitored using Illumina sequencing targeting the 16S rRNA gene. At all sampling points, four phyla, Proteobacteria, Actinobacteria, Chloroflexi, and Acidobacteria, accounted for the majority of taxa. Members of the Chloroflexi phylum dominated low-diversity sites, whereas Proteobacteria dominated high-diversity sites. Methane, nitrogen, iron, and hydrogen oxidizers were detected as well as archaea and metal-resistant bacteria.IMPORTANCE Our study is a comprehensive microbial investigation of the Chimaera ophiolite. DNA has been extracted from 16 sites in the area and has been studied from microbial and geochemical points of view. We describe a microbial community structure that is dependent on terrestrial, serpentinization-driven abiotic H2, which is poorly studied due to the rarity of these environments on Earth.

Self-rating via video communication in children with disability - a feasibility study.

Background: Different barriers may hinder children with developmental disabilities (DD) from having a voice in research and clinical interventions concerning fundamentally subjective phenomena, such as participation. It is not well-investigated if video communication tools have the potential to reduce these barriers. Aim: This study investigated the feasibility of administering a self-rating instrument measuring participation, Picture My Participation (PmP), via a video communication tool (Zoom), to children with DD. Materials and methods: PmP was administered to 17 children with DD (mean age 13 years). The pictorial representations of activities and response options in PmP were displayed in a shared PowerPoint presentation, enabling nonverbal responses with the annotate function in Zoom. Child and interviewer perceptions of the interview were measured through questionnaires developed for the purpose. Results: All the children completed the interview. Most PmP questions were answered, and no adverse events were registered. Technical issues could generally be solved. No special training or expensive equipment was needed for the interviews. Conclusion: Interviewer-guided self-ratings of participation and related constructs through video communication may be a feasible procedure to use with children with DD from age 11. Significance: Offering video communication may increase children's chances to contribute subjective experiences in research and clinical practice.

Traces of Ancient Life in Oceanic Basalt Preserved as Iron-Mineralized Ultrastructures: Implications for Detecting Extraterrestrial Biosignatures.

Benefiting from their adaptability to extreme environments, subsurface microorganisms have been discovered in sedimentary and igneous rock environments on Earth and have been advocated as candidates in the search for extraterrestrial life. In this article, we study iron-mineralized microstructures in calcite-filled veins within basaltic pillows of the late Ladinian Fernazza group (Middle Triassic, 239 Ma) in Italy. These microstructures represent diverse morphologies, including filaments, globules, nodules, and micro-digitate stromatolites, which are similar to extant iron-oxidizing bacterial communities. In situ analyses including Raman spectroscopy have been used to investigate the morphological, elemental, mineralogical, and bond-vibrational modes of the microstructures. According to the Raman spectral parameters, iron minerals preserve heterogeneous ultrastructures and crystallinities, coinciding with the morphologies and precursor microbial activities. The degree of crystallinity usually represents a microscale gradient decreasing toward previously existing microbial cells, revealing a decline of mineralization due to microbial activities. This study provides an analog of possible rock-dwelling subsurface life on Mars or icy moons and advocates Raman spectroscopy as an efficient tool for in situ analyses. We put forward the concept that ultrastructural characteristics of minerals described by Raman spectral parameters corresponding to microscale morphologies could be employed as carbon-lean biosignatures in future space missions.

Decreased axonal transport rates in the Tg2576 APP transgenic mouse: improvement with the gamma-secretase inhibitor MRK-560 as detected by manganese-enhanced MRI.

Neuropil deposition of beta-amyloid (Aß) peptides is believed to be a key event in the neurodegenerative process of Alzheimer's disease (AD). An early and consistent clinical finding in AD is olfactory dysfunction with associated pathology. Interestingly, transgenic amyloid precursor protein (Tg2576) mice also show early amyloid pathology in olfactory regions. Moreover, a recent study indicates that axonal transport is compromised in the olfactory system of Tg2576 mice, as measured by manganese-enhanced magnetic resonance imaging (MEMRI). Here we tested whether the putative axonal transport deficit in the Tg2576 mouse model improves in response to a selective gamma-secretase inhibitor, N-[cis-4-[(4-chlorophenyl)-sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560). Tg2576 mice or wild-type (WT) littermates were treated daily with MRK-560 (30 µmol/kg) or vehicle for 4 (acute) or 29 days (chronic). The subsequent MEMRI analysis revealed a distinct axonal transport dysfunction in the Tg2576 mice compared with its littermate controls. Interestingly, the impairment of axonal transport could be fully reversed by chronic administration of MRK-560, in line with the significantly lowered levels of both soluble and insoluble forms of Aß found in the brain and olfactory bulbs (OBs) following treatment. However, no improvement of axonal transport was observed after acute treatment with MRK-560, where soluble but not insoluble forms of Aß were reduced in the brain and OBs. The present results show that axonal transport is impaired in Tg2576 mice compared with WT controls, as measured by MEMRI. Chronic treatment in vivo with a gamma-secretase inhibitor, MRK-560, significantly reduces soluble and insoluble forms of Aß, and fully reverses the axonal transport dysfunction.

Validation and test-retest repeatability performance of parametric methods for [11C]UCB-J PET.

[11C]UCB-J is a PET radioligand that binds to the presynaptic vesicle glycoprotein 2A. Therefore, [11C]UCB-J PET may serve as an in vivo marker of synaptic integrity. The main objective of this study was to evaluate the quantitative accuracy and the 28-day test-retest repeatability (TRT) of various parametric quantitative methods for dynamic [11C]UCB-J studies in Alzheimer's disease (AD) patients and healthy controls (HC). Eight HCs and seven AD patients underwent two 60-min dynamic [11C]UCB-J PET scans with arterial sampling over a 28-day interval. Several plasma-input based and reference-region based parametric methods were used to generate parametric images using metabolite corrected plasma activity as input function or white matter semi-ovale as reference region. Different parametric outcomes were compared regionally with corresponding non-linear regression (NLR) estimates. Furthermore, the 28-day TRT was assessed for all parametric methods. Spectral analysis (SA) and Logan graphical analysis showed high correlations with NLR estimates. Receptor parametric mapping (RPM) and simplified reference tissue model 2 (SRTM2) BPND, and reference Logan (RLogan) distribution volume ratio (DVR) regional estimates correlated well with plasma-input derived DVR and SRTM BPND. Among the multilinear reference tissue model (MRTM) methods, MRTM1 had the best correspondence with DVR and SRTM BPND. Among the parametric methods evaluated, spectral analysis (SA) and SRTM2 were the best plasma-input and reference tissue methods, respectively, to obtain quantitatively accurate and repeatable parametric images for dynamic [11C]UCB-J PET.

Chromite oxidation by manganese oxides in subseafloor basalts and the presence of putative fossilized microorganisms.

Chromite is a mineral with low solubility and is thus resistant to dissolution. The exception is when manganese oxides are available, since they are the only known naturally occurring oxidants for chromite. In the presence of Mn(IV) oxides, Cr(III) will oxidise to Cr(VI), which is more soluble than Cr(III), and thus easier to be removed. Here we report of chromite phenocrysts that are replaced by rhodochrosite (Mn(II) carbonate) in subseafloor basalts from the Koko Seamount, Pacific Ocean, that were drilled and collected during the Ocean Drilling Program (ODP) Leg 197. The mineral succession chromite-rhodochrosite-saponite in the phenocrysts is interpreted as the result of chromite oxidation by manganese oxides. Putative fossilized microorganisms are abundant in the rhodochrosite and we suggest that the oxidation of chromite has been mediated by microbial activity. It has previously been shown in soils and in laboratory experiments that chromium oxidation is indirectly mediated by microbial formation of manganese oxides. Here we suggest a similar process in subseafloor basalts.

Dubiofossils from a Mars-analogue subsurface palaeoenvironment: The limits of biogenicity criteria.

The search for a fossil record of Earth's deep biosphere, partly motivated by potential analogies with subsurface habitats on Mars, has uncovered numerous assemblages of inorganic microfilaments and tubules inside ancient pores and fractures. Although these enigmatic objects are morphologically similar to mineralized microorganisms (and some contain organic carbon), they also resemble some abiotic structures. Palaeobiologists have responded to this ambiguity by evaluating problematic filaments against checklists of "biogenicity criteria". Here, we describe material that tests the limits of this approach. We sampled Jurassic calcite veins formed through subseafloor serpentinization, a water-rock reaction that can fuel the deep biosphere and is known to have occurred widely on Mars. At two localities ~4 km apart, veins contained curving, branched microfilaments composed of Mg-silicate and Fe-oxide minerals. Using a wide range of analytical techniques including synchrotron X-ray microtomography and scanning transmission electron microscopy, we show that these features meet many published criteria for biogenicity and are comparable to fossilized cryptoendolithic fungi or bacteria. However, we argue that abiotic processes driven by serpentinization could account for the same set of lifelike features, and report a chemical garden experiment that supports this view. These filaments are, therefore, most objectively described as dubiofossils, a designation we here defend from criticism and recommend over alternative approaches, but which nevertheless signifies an impasse. Similar impasses can be anticipated in the future exploration of subsurface palaeo-habitats on Earth and Mars. To avoid them, further studies are required in biomimetic geochemical self-organization, microbial taphonomy and micro-analytical techniques, with a focus on subsurface habitats.

A late Paleoproterozoic (1.74 Ga) deep-sea, low-temperature, iron-oxidizing microbial hydrothermal vent community from Arizona, USA.

Modern marine hydrothermal vents occur in a wide variety of tectonic settings and are characterized by seafloor emission of fluids rich in dissolved chemicals and rapid mineral precipitation. Some hydrothermal systems vent only low-temperature Fe-rich fluids, which precipitate deposits dominated by iron oxyhydroxides, in places together with Mn-oxyhydroxides and amorphous silica. While a proportion of this mineralization is abiogenic, most is the result of the metabolic activities of benthic, Fe-oxidizing bacteria (FeOB), principally belonging to the Zetaproteobacteria. These micro-organisms secrete micrometer-scale stalks, sheaths, and tubes with a variety of morphologies, composed largely of ferrihydrite that act as sacrificial structures, preventing encrustation of the cells that produce them. Cultivated marine FeOB generally require neutral pH and microaerobic conditions to grow. Here, we describe the morphology and mineralogy of filamentous microstructures from a late Paleoproterozoic (1.74 Ga) jasper (Fe-oxide-silica) deposit from the Jerome area of the Verde mining district in central Arizona, USA, that resemble the branching tubes formed by some modern marine FeOB. On the basis of this comparison, we interpret the Jerome area filaments as having formed by FeOB on the deep seafloor, at the interface of weakly oxygenated seawater and low-temperature Fe-rich hydrothermal fluids. We compare the Jerome area filaments with other purported examples of Precambrian FeOB and discuss the implications of their presence for existing redox models of Paleoproterozoic oceans during the "Boring Billion."

Definitions and Operationalization of Mental Health Problems, Wellbeing and Participation Constructs in Children with NDD: Distinctions and Clarifications.

Children with impairments are known to experience more restricted participation than other children. It also appears that low levels of participation are related to a higher prevalence of mental health problems in children with neurodevelopmental disorders (NDD). The purpose of this conceptual paper is to describe and define the constructs mental health problems, mental health, and participation to ensure that future research investigating participation as a means to mental health in children and adolescents with NDD is founded on conceptual clarity. We first discuss the difference between two aspects of mental health problems, namely mental disorder and mental illness. This discussion serves to highlight three areas of conceptual difficulty and their consequences for understanding the mental health of children with NDD that we then consider in the article: (1) how to define mental health problems, (2) how to define and assess mental health problems and mental health, i.e., wellbeing as separate constructs, and (3) how to describe the relationship between participation and wellbeing. We then discuss the implications of our propositions for measurement and the use of participation interventions as a means to enhance mental health (defined as wellbeing). Conclusions: Mental disorders include both diagnoses related to impairments in the developmental period, i.e., NDD and diagnoses related to mental illness. These two types of mental disorders must be separated. Children with NDD, just like other people, may exhibit aspects of both mental health problems and wellbeing simultaneously. Measures of wellbeing defined as a continuum from flourishing to languishing for children with NDD need to be designed and evaluated. Wellbeing can lead to further participation and act to protect from mental health problems.

Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging.

[11C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test-retest repeatability (TRT) of quantitative [11C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [11C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K1) and volume of distribution (VT) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_VB and 2T4k_VB described the [11C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for VT, DVR and SRTM BPND were -2.2% ± 8.5, 0.4% ± 12.0 and -8.0% ± 10.2, averaged over all subjects. [11C]UCB-J kinetics can be well described by a 1T2k_VB model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for VT, DVR and BPND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [11C]UCB-J PET.

Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists for the treatment of sleep disorders.

Scaffold hopping from a non-basic series of 5-HT(2A) receptor antagonists developed in-house that possessed reduced activity in vivo enabled the discovery of a novel series of diaryl sulfones that gave excellent occupancy on oral dosing. Not only does this work further demonstrate that oral bioavailability of a given series can be enhanced by improving physicochemical parameters such as log P, but it corroborates the growing evidence that a protonated amine is not essential for affinity at aminergic GPCRs.

Cost-Effectiveness Analysis of Patiromer in Combination with Renin-Angiotensin-Aldosterone System Inhibitors for Chronic Kidney Disease in Sweden.

OBJECTIVES: Patients with chronic kidney disease (CKD) are commonly treated with renin-angiotensin-aldosterone system inhibitors (RAASi) in order to delay progression of renal disease. However, research has shown that RAASi in CKD patients increases hyperkalaemia (HK) prevalence, which leads to RAASi discontinuation or dose reduction with the loss of benefits on the kidney. Patiromer is a novel therapy for HK treatment and may enable patients to remain on their RAASi regimen. This study aimed to assess the cost-effectiveness of patiromer from a Swedish healthcare perspective. METHODS: A Markov model was developed to evaluate the economic outcomes of patiromer versus no patiromer in HK patients with stage 3-4 CKD taking RAASi. The model consisted of six health states reflecting disease progression and hospitalisations. The analysis mainly considered clinical data from the OPAL-HK trial and national costs. The main outcomes of interest were incremental costs (euro [EUR] 2016) and quality-adjusted life years (QALYs), discounted at 3%, and the incremental cost-effectiveness ratio (ICER). Extensive uncertainty analyses were performed. RESULTS: In comparison to no patiromer, a patiromer patient gained 0.14 QALYs and an incremental cost of EUR 6109 (Swedish krona [SEK] 57,850), yielding an ICER of EUR 43,307 (SEK 410,072)/QALY gained. The results were robust to a range of sensitivity analyses. At a willingness-to-pay threshold of EUR 52,804 (SEK 500,000)/QALY, patiromer had a 50% chance of being cost-effective. CONCLUSIONS: The results indicate that patiromer may demonstrate value for money in Swedish patients with stage 3-4 CKD, by enabling RAASi treatment. However, there is a considerable degree of uncertainty.

Isotope abundance ratio measurements using femtosecond laser ablation ionization mass spectrometry.

Accurate isotope ratio measurements are of high importance in various scientific fields, ranging from radio isotope geochronology of solids to studies of element isotopes fractionated by living organisms. Instrument limitations, such as unresolved isobaric inferences in the mass spectra, or cosampling of the material of interest together with the matrix material may reduce the quality of isotope measurements. Here, we describe a method for accurate isotope ratio measurements using our laser ablation ionization time-of-flight mass spectrometer (LIMS) that is designed for in situ planetary research. The method is based on chemical depth profiling that allows for identifying micrometer scale inclusions embedded in surrounding rocks with different composition inside the bulk of the sample. The data used for precise isotope measurements are improved using a spectrum cleaning procedure that ensures removal of low quality spectra. Furthermore, correlation of isotopes of an element is used to identify and reject the data points that, for example, do not belong to the species of interest. The measurements were conducted using IR femtosecond laser irradiation focused on the sample surface to a spot size of ~12 µm. Material removal was conducted for a predefined number of laser shots, and time-of-flight mass spectra were recorded for each of the ablated layers. Measurements were conducted on NIST SRM 986 Ni isotope standard, trevorite mineral, and micrometer-sized inclusions embedded in aragonite. Our measurements demonstrate that element isotope ratios can be measured with accuracies and precision at the permille level, exemplified by the analysis of B, Mg, and Ni element isotopes. The method applied will be used for in situ investigation of samples on planetary surfaces, for accurate quantification of element fractionation induced by, for example, past or present life or by geochemical processes.

Active immunotherapy and alternative therapeutic modalities for Alzheimer's disease.

As knowledge of Alzheimer's disease (AD) progression improves, the field has recognized the need to diversify the pipeline, broaden strategies and approaches to therapies, as well as delivery mechanisms. A better understanding of the earliest biological processes of AD/dementia would help inform drug target selection. Currently there are a number of programs exploring these alternate avenues. This meeting will allow experts in the field (academia, industry, government) to provide perspectives and experiences that can help elucidate what the pipeline looks like today and what avenues hold promise in developing new therapies across the stages of AD. The focus here is on Active Immunotherapies and Alternative Therapeutic Modalities. This topic includes active vaccines, antisense oligomers, and cell-based therapy among others, and highlights new clinical developments that utilize these modalities.

CoREST Complex-Selective Histone Deacetylase Inhibitors Show Prosynaptic Effects and an Improved Safety Profile To Enable Treatment of Synaptopathies.

Synaptic dysfunction is a pathological feature in many neurodegenerative disorders, including Alzheimer's disease, and synaptic loss correlates closely with cognitive decline. Histone deacetylases (HDACs) are involved in chromatin remodeling and gene expression and have been shown to regulate synaptogenesis and synaptic plasticity, thus providing an attractive drug discovery target for promoting synaptic growth and function. To date, HDAC inhibitor compounds with prosynaptic effects are plagued by known HDAC dose-limiting hematological toxicities, precluding their application to treating chronic neurologic conditions. We have identified a series of novel HDAC inhibitor compounds that selectively inhibit the HDAC-co-repressor of repressor element-1 silencing transcription factor (CoREST) complex while minimizing hematological side effects. HDAC1 and HDAC2 associate with multiple co-repressor complexes including CoREST, which regulates neuronal gene expression. We show that selectively targeting the CoREST co-repressor complex with the representative compound Rodin-A results in increased spine density and synaptic proteins, and improved long-term potentiation in a mouse model at doses that provide a substantial safety margin that would enable chronic treatment. The CoREST-selective HDAC inhibitor Rodin-A thus represents a promising therapeutic strategy in targeting synaptic pathology involved in neurologic disorders.