Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes.

Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help us to understand brain pathophysiology and improve outcomes. Here, we report that adult ablation of autism spectrum disorder (ASD)-associated CHD8 in astrocytes attenuates reactive gliosis via remodeling chromatin accessibility, changing gene expression. Conditional Chd8 deletion in astrocytes, but not microglia, suppresses reactive gliosis by impeding astrocyte proliferation and morphological elaboration. Astrocyte Chd8 ablation alleviates lipopolysaccharide-induced neuroinflammation and septic-associated hypothermia in mice. Astrocytic CHD8 plays an important role in neuroinflammation by altering the chromatin landscape, regulating metabolic and lipid-associated pathways, and astrocyte-microglia crosstalk. Moreover, we show that reactive gliosis can be directly mitigated in vivo using an adeno-associated virus (AAV)-mediated Chd8 gene editing strategy. These findings uncover a role of ASD-associated CHD8 in the adult brain, which may warrant future exploration of targeting chromatin remodelers in reactive gliosis and neuroinflammation in injury and neurological diseases.

Severe Spaceflight-Associated Neuro-Ocular Syndrome in an Astronaut With 2 Predisposing Factors.

Importance: Understanding potential predisposing factors associated with spaceflight-associated neuro-ocular syndrome (SANS) may influence its management. Objective: To describe a severe case of SANS associated with 2 potentially predisposing factors. Design, Setting, and Participants: Ocular testing of and blood collections from a female astronaut were completed preflight, inflight, and postflight in the setting of the International Space Station (ISS). Exposure: Weightlessness throughout an approximately 6-month ISS mission. Mean carbon dioxide (CO2) partial pressure decreased from 2.6 to 1.3 mm Hg weeks before the astronaut's flight day (FD) 154 optical coherence tomography (OCT) session. In response to SANS, 4 B-vitamin supplements (vitamin B6, 100 mg; L-methylfolate, 5 mg; vitamin B12, 1000 µg; and riboflavin, 400 mg) were deployed, unpacked on FD153, consumed daily through FD169, and then discontinued due to gastrointestinal discomfort. Main Outcomes and Measures: Refraction, distance visual acuity (DVA), optic nerve, and macular assessment on OCT. Results: Cycloplegic refraction was -1.00 diopter in both eyes preflight and +0.50 - 0.25 × 015 in the right eye and +1.00 diopter in the left eye 3 days postflight. Uncorrected DVA was 20/30 OU preflight, 20/16 or better by FD90, and 20/15 OU 3 days postflight. Inflight peripapillary total retinal thickness (TRT) peaked between FD84 and FD126 (right eye, 401 µm preflight, 613 µm on FD84; left eye, 404 µm preflight, 636 µm on FD126), then decreased. Peripapillary choroidal folds, quantified by surface roughness, peaked at 12.7 µm in the right eye on FD154 and 15.0 µm in the left eye on FD126, then decreased. Mean choroidal thickness increased throughout the mission. Genetic analyses revealed 2 minor alleles for MTRR 66 and 2 major alleles for SHMT1 1420 (ie, 4 of 4 SANS risk alleles). One-week postflight, lumbar puncture opening pressure was normal, at 19.4 cm H2O. Conclusions and Relevance: To the authors' knowledge, no other report of SANS documented as large of a change in peripapillary TRT or hyperopic shift during a mission as in this astronaut, and this was only 1 of 4 astronauts to experience chorioretinal folds approaching the fovea. This case showed substantial inflight improvement greater than the sensitivity of the measure, possibly associated with B-vitamin supplementation and/or reduction in cabin CO2. However, as a single report, such improvement could be coincidental to these interventions, warranting further evaluation.

Synthesis of Stereodefined Polysubstituted Bicyclo[1.1.0]butanes.

We report a highly diastereoselective synthesis of polysubstituted bicyclobutanes possessing up to three stereodefined quaternary centers and five substituents. Our strategy involves a diastereoselective carbometalation of cyclopropenes followed by a cyclization to furnish the bicyclobutane ring system. This straightforward approach allows for the incorporation of a diverse range of substituents and functional groups, notably without the need for electron-withdrawing functionalities.

Photorefractive Keratectomy and Laser-Assisted In Situ Keratomileusis on 6-Month Space Missions.

BACKGROUND: This article documents the stability of photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) in two astronauts during 6-mo missions to the International Space Station.CASE REPORTS: Ocular examinations including visual acuity, cycloplegic refraction, slit lamp examination, corneal topography, central corneal thickness, optical biometry (axial length/keratometry), applanation tonometry, and dilated fundus examination were performed on each astronaut before and after their missions, and in-flight visual acuity testing was done on flight day 30, 90, and R-30 (30 d before return). They were also questioned regarding visual changes during flight.DISCUSSION: We documented stable vision in both PRK and LASIK astronauts during liftoff, entry into microgravity, 6 mo on the International Space Station, descent, and landing. Our results suggest that both PRK and LASIK are stable and well tolerated during long-duration spaceflight.Gibson CR, Mader TH, Lipsky W, Schallhorn SC, Tarver WJ, Suresh R, Hauge TN, Brunstetter TJ. Photorefractive keratectomy and laser-assisted in situ keratomileusis on 6-month space missions. Aerosp Med Hum Perform. 2024; 95(5):278-281.

Stereoinvertive SN1 Through Neighboring Group Participation.

Neighboring group participation, the assistance of non-conjugated electrons to a reaction center, is a fundamental phenomenon in chemistry. In the framework of nucleophilic substitution reactions, neighboring group participation is known to cause rate acceleration, first order kinetics (SN1), and retention of configuration. The latter phenomenon is a result of double inversion: the first one when the neighboring group displaces the leaving group, and the second when a nucleophile substitutes the neighboring group. This powerful control of stereoretention has been widely used in organic synthesis for more than a century. However, neighboring group participation may also lead to inversion of configuration, a phenomenon which is often overlooked. Herein, we review this unique mode of stereoinversion, dividing the relevant reactions into three classes with the aim to introduce a fresh perspective on the different modes of stereoinversion via neighboring group participation as well as the factors that control this stereochemical outcome.

Immune system dysregulation preceding a case of laboratory-confirmed zoster/dermatitis on board the International Space Station.

A case report detailing, for the first time, a case of laboratory-confirmed zoster in an astronaut on board the International Space Station is presented. The findings of reduced T-cell function, cytokine imbalance, and increased stress hormones which preceded the event are detailed. Relevance for deep space countermeasures is discussed.

Structural and electronic properties of Li-adsorbed single and bilayer porphyrin sheets as an electrode material for energy storage devices - a DFT analysis.

In this study, we adopt density functional theory (DFT) to investigate the structural and electronic properties of monolayer and bilayer 2-D porphyrin sheets (PS) of covalent organic frameworks (COFs) upon interaction with Li atoms as an electrode material for Li-ion batteries. Based on their mechanical properties, our systems exhibit remarkable stability. The adsorption of Li at various sites in the monolayer, including over and between the bilayers of PS, is investigated. Our results indicate that Li at site S3 has the highest adsorption energy, and Li is energetically preferred to intercalate within the bilayer rather than monolayers due to its high adsorption energies. Notably, the charge transfer remains consistent for both systems. The density of state distribution, charge density difference plots, spin density and the band structure results show that the PS has high electrical conductivity. Additionally, the reaction potential was carried out, and the negative reaction potential results demonstrate that the system undergoes a reduction reaction. The resultant theoretical capacity and the open circuit voltage highlight that the PS materials of COFs are an important step for use in the next generation high-performance lithium-ion batteries.

Superatom molecular orbital in C80.

The Superatom Molecular Orbitals (SAMO) in fullerene derivatives are of great interests which gives a wide basement for many electronic applications. In this work, the Density Functional Theory reveals the SAMO states of endohedrally doped C80 derivatives with Li, Sc, Mn, Ti, Ca, Fe, and Co atoms in molecular and periodic structures. The choice and position of metal atoms in endohedrally doped C80 derivatives largely affects the orientation of SAMO energies and wavefunction distributions. Among various derivatives, the Co-substituted C80 constitutes the lowest SAMO energy. The charge transfer study infers the influence of metal atoms inside the cage on SAMO energies. At higher energies, pz-, 2s-, and pxy- SAMO bands have been overlapped with higher dispersion bands which depict the increased intermolecular interaction in delocalized bands causing a larger dispersion. These results give new insights for future studies on lowering SAMO energy nearly to the fermi level in higher fullerenes.

Superatom Molecular Orbitals of Endohedral C82.

Understanding superatom molecular orbital (SAMO) states in fullerene derivatives has been in the limelight ever since the first discovery of SAMOs owing to the fundamental interest in this topic as well as to the possible applications in molecular switches and other organic electronics. Nevertheless, very few reports have been published on SAMO states of larger fullerenes so far. Using density functional theory, we attempt to partially remedy this situation by presenting a study on SAMO states in C82 and its Ca and Sc endohedrally doped derivatives, comparing results with previous relevant findings for C60. We find that C82 possesses higher SAMO energies compared to C60, as associated with the symmetry of the molecule, and that endohedral doping leads to energetically favorable side positions of Ca and Sc inside the C82 cage. Among the two, Sc@C82 has more stable SAMO states compared to Ca@C82 as reflected by the shift in the density of states, while the charge states are found to be similar. In the case of the monolayer form, the pz- and 2s-SAMO orbitals overlap with the nearest neighbors, causing parabolic band dispersion with the formation of near free electron states and that the SAMO state energies move closer to the Fermi energy compared to the related molecules. These findings provide promising information about the distribution of SAMO states in C82 fullerene, which can be further relevant in studies of SAMO states of higher fullerenes and for coming applications of these systems.

Hydrogen Bonds in Lead Halide Perovskites: Insights from Ab Initio Molecular Dynamics.

Hydrogen bonds (HBs) play an important role in the rotational dynamics of organic cations in hybrid organic/inorganic halide perovskites, thus affecting the structural and electronic properties of the perovskites. However, the properties and even the existence of HBs in these perovskites are not well established. In this study, we investigate HBs in perovskites MAPbBr3 (MA+ = CH3NH3+), FAPbI3 (FA+ = CH(NH2)2+), and their solid solution with composition (FAPbI3)7/8(MAPbBr3)1/8, using ab initio molecular dynamics and electronic structure calculations. We consider HBs donated by X-H fragments (X = N and C) of the organic cations and accepted by the halides (Y = Br and I) and characterize their properties based on pair distribution functions and on a combined distribution function of the hydrogen-acceptor distance with the donor-hydrogen-acceptor angle. By analyzing these functions, we establish geometrical criteria for HB existence based on the hydrogen-acceptor (H-Y) distance and donor-hydrogen-acceptor angle (X-H-Y). The distance condition is defined as d(H - Y) < 3 Å for N-H-donated HBs and d(H - Y) < 4 Å for C-H-donated HBs. The angular condition is 135° < (X - H - Y) < 180° for both types of HBs. A HB is considered to be formed when both angular and distance conditions are simultaneously satisfied. At the simulated temperature (350 K), the HBs dynamically break and form. We compute the time correlation functions of HB existence and HB lifetimes, which range between 0.1 and 0.3 ps at that temperature. The analysis of HB lifetimes indicates that N-H-Br bonds are relatively stronger than N-H-I bonds, while C-H-Y bonds are weaker, with a minimal influence from the halide and cation. To evaluate the impact of HBs on the vibrational spectra, we present the power spectrum in the region of N-H and C-H stretching modes, comparing them with the normal mode frequencies of isolated cations. We show that the peaks associated with N-H stretching modes in perovskites are redshifted and asymmetrically deformed, while the C-H peaks do not exhibit these effects.

Selecting Medical Conditions Relevant to Exploration Spaceflight to Create the IMPACT 1.0 Medical Condition List.

INTRODUCTION: Medical conditions occurring in spaceflight pose risks to the crew and the mission and these risks will be exacerbated during exploration-class missions. Probabilistic risk assessment is a method used at NASA to quantify this risk for low-Earth orbit operations. Informing Mission Planning via Analysis of Complex Tradespaces (IMPACT) is a next-generation tool suite that will perform these assessments for exploration-class missions. It will require a robust list of medical conditions of significant likelihood and/or consequence to exploration-class missions to accurately inform the tool suite.METHODS: The IMPACT 1.0 Medical Condition List (ICL 1.0) contains 120 conditions selected in the context of a 210-d cis-lunar, Mars analog design reference mission. The conditions were selected via a systematic process that preserved institutional knowledge from nine prior condition lists. Conditions were prioritized for inclusion in the ICL 1.0 based on history of occurrence in spaceflight, concurrence among the nine source lists, and concurrence among subject matter experts.DISCUSSION: The ICL 1.0 has notable advantages over its predecessor lists in that it is more specific to exploration-class missions, contains a greater number, breadth, and depth of conditions, and was derived via consensus across multiple medical specialties.Kreykes AJ, Suresh R, Levin D, Hilmers DC. Selecting medical conditions relevant to exploration spaceflight to create the IMPACT 1.0 Medical Condition List. Aerosp Med Hum Perform. 2023; 94(7):550-557.

Reversibility and therapeutic development for neurodevelopmental disorders, insights from genetic animal models.

Neurodevelopmental Disorders (NDDs) encompass a broad spectrum of conditions resulting from atypical brain development. Over the past decades, we have had the fortune to witness enormous progress in diagnosis, etiology discovery, modeling, and mechanistic understanding of NDDs from both fundamental and clinical research. Here, we review recent neurobiological advances from experimental models of NDDs. We introduce several examples and highlight breakthroughs in reversal studies of phenotypes using genetically engineered models of NDDs. The in-depth understanding of brain pathophysiology underlying NDDs and evaluations of reversibility in animal models paves the foundation for discovering novel treatment options. We discuss how the expanding property of cutting-edge technologies, such as gene editing and AAV-mediated gene delivery, are leveraged in animal models for the therapeutic development of NDDs. We envision opportunities and challenges toward faithful modeling and fruitful clinical translation.

Cyclo[18]carbon Formation from C18Br6 and C18(CO)6 Precursors.

Although cyclo[18]carbon has been isolated experimentally from two precursors, C18Br6 and C18(CO)6, no reaction mechanisms have yet been explored. Herein, we provide insight into the mechanism behind debromination and decarbonylation. Both neutral precursors demonstrate high activation barriers of ∼2.3 eV, while the application of an electric field can lower the barriers by 0.1-0.2 eV. The barrier energy of the anion-radicals is found to be significantly lower for C18Br6 compared to C18(CO)6, confirming a considerably higher yield of cylco[18]carbon when the C18Br6 precursor is used. Elongation of the C-Br bond in the anion-radical confirms its predissociation condition. Natural bonding orbital analysis shows that the stability of C-Br and C-CO bonds in the anion-radicals is lower compared to their neutral species, indicating a possible higher yield. The applied analysis provides crucial details regarding the reaction yield of cyclo[18]carbon and can serve as a general scheme for tuning reaction conditions for other organic precursors.

Scoping review to evaluate the effects of peer support on the mental health of young adults.

OBJECTIVES: Young adults report disproportionality greater mental health problems compared with the rest of the population with numerous barriers preventing them from seeking help. Peer support, defined as a form of social-emotional support offered by an individual with a shared lived experience, has been reported as being effective in improving a variety of mental health outcomes in differing populations. The objective of this scoping review is to provide an overview of the literature investigating the impact of peer support on the mental health of young adults. DESIGN: A scoping review methodology was used to identify relevant peer-reviewed articles in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines across six databases and Google/Google Scholar. Overall, 17 eligible studies met the inclusion criteria and were included in the review. RESULTS: Overall, studies suggest that peer support is associated with improvements in mental health including greater happiness, self-esteem and effective coping, and reductions in depression, loneliness and anxiety. This effect appears to be present among university students, non-student young adults and ethnic/sexual minorities. Both individual and group peer support appear to be beneficial for mental health with positive effects also being present for those providing the support. CONCLUSIONS: Peer support appears to be a promising avenue towards improving the mental health of young adults, with lower barriers to accessing these services when compared with traditional mental health services. The importance of training peer supporters and the differential impact of peer support based on the method of delivery should be investigated in future research.

Santalol Isomers Inhibit Transthyretin Amyloidogenesis and Associated Pathologies in Caenorhabditis elegans.

Transthyretin (TTR) is a homotetrameric protein found in human serum and is implicated in fatal inherited amyloidoses. Destabilization of native TTR confirmation resulting from mutation, environmental changes, and aging causes polymerization and amyloid fibril formation. Although several small molecules have been reported to stabilize the native state and inhibit TTR aggregation, prolonged use can cause serious side effects. Therefore, pharmacologically enhancing the degradation of TTR aggregates and kinetically stabilizing the native tetrameric structure with bioactive molecule(s) could be a viable therapeutic strategy to hinder the advancement of TTR amyloidoses. In this context, here we demonstrated α- and ß-santalol, natural sesquiterpenes from sandalwood, as a potent TTR aggregation inhibitor and native state stabilizer using combined in vitro, in silico, and in vivo experiments. We found that α- and ß-santalol synergize to reduce wild-type (WT) and Val30Met (V30M) mutant TTR aggregates in novel C. elegans strains expressing TTR fragments fused with a green fluorescent protein in body wall muscle cells. α- and ß-Santalol extend the lifespan and healthspan of C. elegans strains carrying TTRWT::EGFP and TTRV30M::EGFP transgene by activating the SKN-1/Nrf2, autophagy, and proteasome. Moreover, α- and ß-santalol directly interacted with TTR and reduced the flexibility of the thyroxine-binding cavity and homotetramer interface, which in turn increases stability and prevents the dissociation of the TTR tetramer. These data indicate that α- and ß-santalol are the strong natural therapeutic intervention against TTR-associated amyloid diseases.

Predicting quorum sensing peptides using stacked generalization ensemble with gradient boosting based feature selection.

Bacteria exist in natural environments for most of their life as complex, heterogeneous, and multicellular aggregates. Under these circumstances, critical cell functions are controlled by several signaling molecules known as quorum sensing (QS) molecules. In Gram-positive bacteria, peptides are deployed as QS molecules. The development of antibodies against such QS molecules has been identified as a promising therapeutic intervention for bacterial control. Hence, the identification of QS peptides has received considerable attention. Availability of a fast and reliable predictive model to effectively identify QS peptides can help the existing high throughput experiments. In this study, a stacked generalization ensemble model with Gradient Boosting Machine (GBM)-based feature selection, namely EnsembleQS was developed to predict QS peptides with high accuracy. On selected GBM features (791D), the EnsembleQS outperformed finely tuned baseline classifiers and demonstrated robust performance, indicating the superiority of the model. The accuracy of EnsembleQS is 4% higher than those resulting from ensemble model on hybrid dataset. When evaluating an independent data set of 40 QS peptides, the EnsembleQS model showed an accuracy of 93.4% with Matthew's Correlation Coefficient (MCC) and area under the ROC curve (AUC) values of 0.91 and 0.951, respectively. These results suggest that EnsembleQS will be a useful computational framework for predicting QS peptides and will efficiently support proteomics research. The source code and all datasets used in this study are publicly available at https://github.com/proteinexplorers/EnsembleQS .

Autosegmentation based on different-sized training datasets of consistently-curated volumes and impact on rectal contours in prostate cancer radiation therapy.

Background and purpose: Autosegmentation techniques are emerging as time-saving means for radiation therapy (RT) contouring, but the understanding of their performance on different datasets is limited. The aim of this study was to determine agreement between rectal volumes by an existing autosegmentation algorithm and manually-delineated rectal volumes in prostate cancer RT. We also investigated contour quality by different-sized training datasets and consistently-curated volumes for retrained versions of this same algorithm. Materials and methods: Single-institutional data from 624 prostate cancer patients treated to 50-70 Gy were used. Manually-delineated clinical rectal volumes (clinical) and consistently-curated volumes recontoured to one anatomical guideline (reference) were compared to autocontoured volumes by a commercial autosegmentation tool based on deep-learning (v1; n = 891, multiple-institutional data) and retrained versions using subsets of the curated volumes (v32/64/128/256; n = 32/64/128/256). Evaluations included dose-volume histogram metrics, Dice similarity coefficients, and Hausdorff distances; differences between groups were quantified using parametric or non-parametric hypothesis testing. Results: Volumes by v1-256 (76-78 cm3) were larger than reference (75 cm3) and clinical (76 cm3). Mean doses by v1-256 (24.2-25.2 Gy) were closer to reference (24.2 Gy) than to clinical (23.8 Gy). Maximum doses were similar for all volumes (65.7-66.0 Gy). Dice for v1-256 and reference (0.87-0.89) were higher than for v1-256 and clinical (0.86-0.87) with corresponding Hausdorff comparisons including reference smaller than comparisons including clinical (5-6 mm vs. 7-8 mm). Conclusion: Using small single-institutional RT datasets with consistently-defined rectal volumes when training autosegmentation algorithms created contours of similar quality as the same algorithm trained on large multi-institutional datasets.

MicroRNA-210 regulates the metabolic and inflammatory status of primary human astrocytes.

BACKGROUND: Astrocytes are the most numerous glial cell type with important roles in maintaining homeostasis and responding to diseases in the brain. Astrocyte function is subject to modulation by microRNAs (miRs), which are short nucleotide strands that regulate protein expression in a post-transcriptional manner. Understanding the miR expression profile of astrocytes in disease settings provides insight into the cellular stresses present in the microenvironment and may uncover pathways of therapeutic interest. METHODS: Laser-capture microdissection was used to isolate human astrocytes surrounding stroke lesions and those from neurological control tissue. Astrocytic miR expression profiles were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Primary human fetal astrocytes were cultured under in vitro stress conditions and transfection of a miR mimic was used to better understand how altered levels of miR-210 affect astrocyte function. The astrocytic response to stress was studied using qPCR, enzyme-linked immunosorbent assays (ELISAs), measurement of released lactate, and Seahorse. RESULTS: Here, we measured miR expression levels in astrocytes around human ischemic stroke lesions and observed differential expression of miR-210 in chronic stroke astrocytes compared to astrocytes from neurological control tissue. We also identified increased expression of miR-210 in mouse white matter tissue around middle cerebral artery occlusion (MCAO) brain lesions. We aimed to understand the role of miR-210 in primary human fetal astrocytes by developing an in vitro assay of hypoxic, metabolic, and inflammatory stresses. A combination of hypoxic and inflammatory stresses was observed to upregulate miR-210 expression. Transfection with miR-210-mimic (210M) increased glycolysis, enhanced lactate export, and promoted an anti-inflammatory transcriptional and translational signature in astrocytes. Additionally, 210M transfection resulted in decreased expression of complement 3 (C3) and semaphorin 5b (Sema5b). CONCLUSIONS: We conclude that miR-210 expression in human astrocytes is modulated in response to ischemic stroke disease and under in vitro stress conditions, supporting a role for miR-210 in the astrocytic response to disease conditions. Further, the anti-inflammatory and pro-glycolytic impact of miR-210 on astrocytes makes it a potential candidate for further research as a neuroprotective agent.

Expression of cell type incongruent alpha-cardiac actin 1 subunit in medulloblastoma reveals a novel mechanism for cancer cell survival and control of migration.

BACKGROUND: Alterations in actin subunit expression have been reported in multiple cancers, but have not been investigated previously in medulloblastoma. METHODS: Bioinformatic analysis of multiple medulloblastoma tumor databases was performed to profile ACTC1 mRNA levels. Western blot was used to verify protein expression in established medulloblastoma cell lines. Immunofluorescence microscopy was performed to assess ACTC1 localization. Stable cell lines with ACTC1 overexpression were generated and shRNA knockdown of ACTC1 was accomplished. We used PARP1 cleavage by Western blot as a marker of apoptosis and cell survival was determined by FACS viability assay and colony formation. Cell migration with overexpression or knockdown of ACTC1 was determined by the scratch assay. Stress fiber length distribution was assessed by fluorescence microscopy. RESULTS: ACTC1 mRNA expression is highest in SHH and WNT medulloblastoma among all subgroups. ACTC1 protein was confirmed by Western blot in SHH subgroup and Group 3 subgroup cell lines with the lowest expression in Group 3 cells. Microscopy demonstrated ACTC1 co-localization with F-actin. Overexpression of ACTC1 in Group 3 cells abolished the apoptotic response to Aurora kinase B inhibition. Knockdown of ACTC1 in SHH cells and in Myc overexpressing SHH cells induced apoptosis, impaired colony formation, and inhibited migration. Changes in stress fiber length distribution in medulloblastoma cells are induced by alterations in ACTC1 abundance. CONCLUSIONS: Alpha-cardiac actin (ACTC1) is expressed in SHH medulloblastoma. Expression of this protein in medulloblastoma modifies stress fiber composition and functions in promoting resistance to apoptosis induced by mitotic inhibition, enhancing cell survival, and controlling migration.