Full configurational and conformational analysis of artemisinin by one-bond carbon-carbon residual dipolar couplings at natural abundance.

Configurational and conformational analysis of the biologically relevant natural product artemisinin was conducted using carbon-carbon residual dipolar couplings (1DCC RDCs) at natural abundance. These RDCs were measured through the 2D-INADEQUATE NMR experiment using a sample aligned in a compressed poly (methyl methacrylate) (PMMA) gel swollen in CDCl3. Singular value decomposition (SVD) fitting analysis of all carbon-carbon bonds, 1DCC RDCs, in relation to the full configuration/conformational space (32 diastereoisomers) of artemisinin, unambiguously identified the correct configuration of artemisinin.

The Prediction and Treatment of Bleeding Esophageal Varices in the Artificial Intelligence Era: A Review.

Esophageal varices (EVs), a significant complication of cirrhosis, present a considerable challenge in clinical practice due to their high risk of bleeding and associated morbidity and mortality. This manuscript explores the transformative role of artificial intelligence (AI) in the management of EV, particularly in enhancing diagnostic accuracy and predicting bleeding risks. It underscores the potential of AI in offering noninvasive, efficient alternatives to traditional diagnostic methods such as esophagogastroduodenoscopy (EGD). The complexity of EV management is highlighted, necessitating a multidisciplinary approach that includes pharmacological therapy, endoscopic interventions, and, in some cases, surgical options tailored to individual patient profiles. Additionally, the paper emphasizes the importance of integrating AI into medical education and practice, preparing healthcare professionals for the evolving landscape of medical technology. It projects a future where AI significantly influences the management of gastrointestinal bleeding, improving clinical decision-making, patient outcomes, and overall healthcare efficiency. The study advocates for a patient-centered approach in healthcare, balancing the incorporation of innovative technologies with ethical principles and the diverse needs of patients to optimize treatment efficacy and enhance healthcare accessibility.

Distal Transradial Access in the Anatomical Snuffbox for Interventional Coronary Procedures: Analysis of Access Site Pain and Complications.

INTRODUCTION: A novel arterial access distally on the radial artery through the anatomical snuffbox has been recently described for coronary interventional procedures. However, there is insufficient data comparing the advantages and limitations of distal transradial access (dTRA), conventional transradial access (TRA), and transfemoral access (TFA). The aim of this study was to compare the three access sites regarding local pain and complications during or after coronary interventional procedures. METHODS: This prospective observational single-center study included 211 patients undergoing cardiac catheterization or percutaneous coronary intervention, divided into three groups: dTRA (n=69), TRA (n=71), and TFA (n=71). The access site was chosen at the discretion of three operators. We administered a questionnaire to all patients, addressing local pain or discomfort during or after the procedure and the occurrence of possible complications such as distal pallor, local bleeding, and purple color on the access site. RESULTS: Pain on the access site during the procedure was reported more frequently in the TRA group (dTRA 15.9% vs. TRA 32.4% vs. TFA 15.5%). There were no differences in the occurrence of local pain after the procedure in all three groups (29.6% in the dTRA group, 28.2% in the TRA group, and 26.8% in the TFA group). Pain intensity, when it occurred, was higher in the dTRA group (dTRA 5.8 vs. TRA 4.8 vs. TFA 4.6 on a 1-10 scale), as was its duration (dTRA 13.7 vs. TRA 7.6 vs. TFA 8.2 days). Only two local bleeding events were reported, both in the TFA group. No major complications were recorded. CONCLUSION: The occurrence of local pain on the puncture site after coronary interventional procedures did not differ among the three groups. The dTRA group presented a lower incidence of pain during the procedure when compared to TRA and a lower incidence of purple color when compared to TFA. However, pain intensity and duration were higher in the dTRA group when pain was reported. Using dTRA for coronary procedures is a feasible and safe strategy in selected cases.

Distal transradial access in the anatomical snuffbox for interventional coronary procedures: analysis of access site pain and complications

INTRODUCTION: A novel arterial access distally on the radial artery through the anatomical snuffbox has been recently described for coronary interventional procedures. However, there is insufficient data comparing the advantages and limitations of distal transradial access (dTRA), conventional transradial access (TRA), and transfemoral access (TFA). The aim of this study was to compare the three access sites regarding local pain and complications during or after coronary interventional procedures. METHODS: This prospective observational single-center study included 211 patients undergoing cardiac catheterization or percutaneous coronary intervention, divided into three groups: dTRA (n=69), TRA (n=71), and TFA (n=71). The access site was chosen at the discretion of three operators. We administered a questionnaire to all patients, addressing local pain or discomfort during or after the procedure and the occurrence of possible complications such as distal pallor, local bleeding, and purple color on the access site. RESULTS: Pain on the access site during the procedure was reported more frequently in the TRA group (dTRA 15.9% vs. TRA 32.4% vs. TFA 15.5%). There were no differences in the occurrence of local pain after the procedure in all three groups (29.6% in the dTRA group, 28.2% in the TRA group, and 26.8% in the TFA group). Pain intensity, when it occurred, was higher in the dTRA group (dTRA 5.8 vs. TRA 4.8 vs. TFA 4.6 on a 1-10 scale), as was its duration (dTRA 13.7 vs. TRA 7.6 vs. TFA 8.2 days). Only two local bleeding events were reported, both in the TFA group. No major complications were recorded. CONCLUSION: The occurrence of local pain on the puncture site after coronary interventional procedures did not differ among the three groups. The dTRA group presented a lower incidence of pain during the procedure when compared to TRA and a lower incidence of purple color when compared to TFA. However, pain intensity and duration were higher in the dTRA group when pain was reported. Using dTRA for coronary procedures is a feasible and safe strategy in selected cases.

Regioselective Hydroxylation of Unsymmetrical Ketones Using Cu, H2O2, and Imine Directing Groups via Formation of an Electrophilic Cupric Hydroperoxide Core.

Herein, we describe the regioselective functionalization of unsymmetrical ketones using imine directing groups, Cu, and H2O2. The C-H hydroxylation of the substrate-ligands derived from 2-substituted benzophenones occurred exclusively at the γ-position of the unsubstituted ring due to the formation of only one imine stereoisomer. Conversely, the imines derived from 4-substituted benzophenones produced E/Z mixtures that upon reacting with Cu and H2O2 led to two γ-C-H hydroxylation products. Contrary to our initial hypothesis, the ratio of the hydroxylation products did not depend on the ratio of the E/Z isomers but on the electrophilicity of the reactive [LCuOOH]1+. A detailed mechanistic analysis suggests a fast isomerization of the imine substrate-ligand binding the CuOOH core before the rate-determining electrophilic aromatic hydroxylation. Varying the benzophenone substituents and/or introducing electron-donating and electron-withdrawing groups on the 4-position of pyridine of the directing group allowed for fine-tuning of the electrophilicity of the mononuclear [LCuOOH]1+ to reach remarkable regioselectivities (up to 91:9 favoring the hydroxylation of the electron-rich arene ring). Lastly, we performed the C-H hydroxylation of alkyl aryl ketones, and like in the unsymmetrical benzophenones, the regioselectivity of the transformations (sp3 vs sp2) could be controlled by varying the electronics of the substrate and/or the directing group.

Production of Escovopsis conidia and the potential use of this parasitic fungus as a biological control agent of leaf-cutting ant fungus gardens.

This study was carried out to investigate the use of different substrates for the production of Escovopsis conidia and verify the virulence of four different isolates cultured on four types of substrates using a novel bioassay. Escovopsis isolates were molecularly identified, based on Internal Transcribed Spacer (ITS) nucleotide sequences. To evaluate conidial production, suspensions (1 × 106 conidia mL-1) of each Escovopsis isolate were inoculated onto four substrates (parboiled rice, white rice, rolled oats, and corn grits). After 14 days, conidial yields were assessed. The virulence of each isolate cultured on the four substrates was tested against Leucoagaricus fungus garden fragments, by directly applying 500 µL of each conidial suspension (1 × 107 conidia mL-1), and the development of the parasite was monitored daily until it completely colonized the fungus garden. It was observed that rolled oats were the best substrate for conidial production, with a yield of 1.7 × 107 to 2.0 × 108 conidia mL-1. Furthermore, isolate AT-01 produced the highest number of conidia when compared with the other isolates. Regardless of the substrate used to produce AT-01 conidia, this isolate completely colonized the fungus garden 6 days post inoculation (dpi), followed by AT-02, AC-01, and AC-2. High levels of both conidial production and virulence against the leaf-cutting ant fungus garden were observed here.

Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche.

Immune tolerance is maintained in lymphoid organs (LOs). Despite the presence of complex immune cell networks in non-LOs, it is unknown whether self-tolerance is maintained in these tissues. We developed a technique to restrict genetic recombination to regulatory T cells (Tregs) only in skin. Selective depletion of skin Tregs resulted in T cell-mediated inflammation of hair follicles (HFs). Suppression did not rely on CTLA-4, but instead on high-affinity interleukin-2 (IL-2) receptor expression by skin Tregs, functioning exclusively in a cell-extrinsic manner. In a novel model of HF stem cell (HFSC)-driven autoimmunity, we reveal that skin Tregs immunologically protect the HFSC niche. Finally, we used spatial transcriptomics to identify aberrant IL-2 signaling at stromal-HF interfaces in a rare form of human alopecia characterized by HFSC destruction and alopecia areata. Collectively, these results reveal the fundamental biology of Tregs in skin uncoupled from the systemic pool and elucidate a mechanism of self-tolerance.

Effect of a calcium silicate cement and experimental glass ionomer cements containing calcium orthophosphate particles on demineralized dentin.

OBJECTIVE: The study aims to evaluate the effect of a glass ionomer cement (GIC; Fuji 9 Gold Label, GC) with added calcium orthophosphate particles and a calcium silicate cement (CSC; Biodentine, Septodont) regarding ion release, degradation in water, mineral content, and mechanical properties of demineralized dentin samples. METHODS: GIC, GIC + 5% DCPD (dicalcium phosphate dihydrate), GIC + 15% DCPD, GIC + 5% ß-TCP (tricalcium phosphate), GIC + 15% ß-TCP (by mass), and CSC were evaluated for Ca2+/Sr2+/F- release in water for 56 days. Cement mass loss was evaluated after 7-day immersion in water. Partially demineralized dentin disks were kept in contact with materials while immersed in simulated body fluid (SBF) at 37 °C for 56 days. The "mineral-to-matrix ratio" (MMR) was determined by ATR-FTIR spectroscopy. Dentin hardness and elastic modulus were obtained by nanoindentation. Samples were observed under scanning and transmission electron microscopy. Data were analyzed by ANOVA/Tukey test (α = 0.05). RESULTS: Ca2+ release from CSC and GIC (µg/cm2) were 4737.0 ± 735.9 and 13.6 ± 1.6, respectively. In relation to the unmodified GIC, the addition of DCPD or ß-TCP increased ion release (p < 0.001). Only the dentin disks in contact with CSC presented higher MMR (p < 0.05) and mechanical properties than those restored with a resin composite used as control (p < 0.05). Mass loss was similar for GIC and CSC; however, the addition of DCPD or ß-TCP increased GIC degradation (p < 0.05). CONCLUSION: Despite the increase in ion release, the additional Ca2+ sources did not impart remineralizing capability to GIC. Both unmodified GIC and CSC showed similar degradation in water. CLINICAL RELEVANCE: CSC was able to promote dentin remineralization.

Epigenetic control of adamantinomatous craniopharyngiomas.

INTRODUCTION: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking. OBJECTIVE: To identify methylation signatures in ACPs regarding clinical presentation and outcome. METHODS: Clinical and pathology data were collected from 35 ACP patients (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multi-dimensional scaling. Statistical associations between clusters and clinical features were achieved using Fisher's test and global biological process interpretations were aided by Gene Ontology enrichment analyses. RESULTS: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = 0.0006), hypomethylated in CpG Island (CGI), non-CGI sites, and globally (P < 0.001), and associated with greater tumor size (24.1 vs 9.5cm3, P = 0.04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell-adhesion, cytoskeleton organization, and cytokine binding, and also cell-type specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation. CONCLUSION: Two clusters of ACP patients were consistently revealed by unsupervised machine learning methods, being one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment.

Glass ionomer cement with calcium-releasing particles: Effect on dentin mineral content and mechanical properties.

OBJECTIVE: to evaluate the effect a glass ionomer cement (GIC) containing hydroxyapatite (HAp) or calcium silicate (CaSi) particles on mineral content and mechanical properties of demineralized dentin. Ion release and compressive strength (CS) of the cements were also evaluated. METHODS: GIC (Fuji 9 Gold Label, GC), GIC+ 5%HAp and GIC+ 5%CaSi (by mass) were evaluated. Ion release was determined by induced coupled plasma optical emission spectroscopy (Ca2+/Sr2+) or ion-specific electrode (F-) (n = 3). A composite (Filtek Z250, 3 M ESPE) was used as control in remineralization tests. Demineralized dentin discs were kept in contact with materials in simulated body fluid (SBF) at 37 °C for eight weeks. Mineral:matrix ratio (MMR) was determined by ATR-FTIR spectroscopy (n = 5). Dentin hardness (H) and elastic modulus (E) were determined by nanoindentation (n = 10). CS was tested after 24 h and 7d in deionized water (n = 12). Data were analyzed by ANOVA/Tukey test (α = 0.05). RESULTS: Ca2+ and Sr2+ release was higher for the modified materials (p < 0.05). Only GIC+ 5%HAp showed higher F- release than the control (p < 0.05). All groups showed statistically significant increases in MMR, with no differences among them after 8 weeks (p > 0.05). No differences in dentin H or E were observed among groups (p > 0.05). HAp-modified GIC showed increased initial CS, while adding CaSi had the opposite effect (p < 0.05). After 7 days, GIC+ 5%CaSi presented lower CS in relation to control and GIC+ 5%HAp (p < 0.05). SIGNIFICANCE: GIC modification with HAp or CaSi affected CS and increased ion release; however, none of the groups showed evidence of dentin remineralization in comparison to the negative control.

Proteomics approach reveals urinary markers for early pregnancy diagnosis in buffaloes.

This study aimed to compare urine proteomics from non- and pregnant buffaloes in order to identify potential biomarkers of early pregnancy. Forty-four females underwent hormonal ovulation synchronization and were randomly divided into two experimental groups: inseminated (n = 30) and non-inseminated (n = 14). The pregnant females were further divided into two groups: pregnant at Day 12 (P12; n = 8) and at Day 18 (P18; n = 8) post-ovulation. The non-pregnant group was also subdivided into two groups: non-pregnant at Day 12 (NP12; n = 7) and at Day 18 (NP18; n = 7). Urine was collected from all females on Days 12 or 18. The samples were processed for proteomics. A total of 798 proteins were reported in the urine considering all groups. The differential proteins play essential roles during pregnancy, acting in cellular transport and metabolism, endometrial remodeling, embryonic protection, and degradation of defective proteins. We suggest that some proteins from our study can be considered biomarkers for early pregnancy diagnosis, since they were increased in pregnant buffaloes. SIGNIFICANCE: Macromolecules have been studied for early pregnancy diagnosis, aiming to increase reproductive efficiency in cattle and buffaloes. Direct methods such as rectal palpation and ultrasonography have been considered late. Thus, this study aimed to compare urine proteomics from non- and pregnant buffaloes to identify potential biomarkers of early pregnancy. The differential proteins found in our study play essential roles during pregnancy, acting in cellular transport and metabolism, endometrial remodeling, embryonic protection, and degradation of defective proteins. We suggest that these proteins can be considered possible biomarkers for early pregnancy diagnosis since they were increased in the pregnant buffaloes.

Outcomes of lower trapezius transfer with hamstring tendons for irreparable rotator cuff tears.

Background: The aim of this study was to evaluate the results of the transfer of the lower trapezius with a graft from hamstring tendons in the treatment of irreparable rotator cuff tears . Level IV; Case Series; Treatment Study. Methods: Ten patients diagnosed with irreparable tears of the supraspinatus and infraspinatus tendons, were evaluated retrospectively -preoperatively, 6 and 12 months postoperatively. They underwent transfer of the prolonged lower trapezius with an autologous graft of the knee flexor tendons. Results: The Shoulder Subjective Value increased from 47 (preoperative) to 71 (1 year after surgery), American Shoulder and Elbow Surgeons Score increased from 26.63 to 75.24. Pain improved from 7.9 to 2.5 on the Visual Analogue Scale. The mean lateral rotation improved from 31° to 51°, flexion from 84° to 122°, and abduction from 76° to 101°. These results have not changed significantly between 6 and 12 months. Discussion: The transfer of the lower trapezius with autologous grafts from the hamstring tendons showed good results in patients under 65 years of age with irreparable rotator cuff tears . Longer follow-up and a greater number of cases are necessary to confirm the efficacy of the transfer.

SeQual-Stream: approaching stream processing to quality control of NGS datasets.

BACKGROUND: Quality control of DNA sequences is an important data preprocessing step in many genomic analyses. However, all existing parallel tools for this purpose are based on a batch processing model, needing to have the complete genetic dataset before processing can even begin. This limitation clearly hinders quality control performance in those scenarios where the dataset must be downloaded from a remote repository and/or copied to a distributed file system for its parallel processing. RESULTS: In this paper we present SeQual-Stream, a streaming tool that allows performing multiple quality control operations on genomic datasets in a fast, distributed and scalable way. To do so, our approach relies on the Apache Spark framework and the Hadoop Distributed File System (HDFS) to fully exploit the stream paradigm and accelerate the preprocessing of large datasets as they are being downloaded and/or copied to HDFS. The experimental results have shown significant improvements in the execution times of SeQual-Stream when compared to a batch processing tool with similar quality control features, providing a maximum speedup of 2.7[Formula: see text] when processing a dataset with more than 250 million DNA sequences, while also demonstrating good scalability features. CONCLUSION: Our solution provides a more scalable and higher performance way to carry out quality control of large genomic datasets by taking advantage of stream processing features. The tool is distributed as free open-source software released under the GNU AGPLv3 license and is publicly available to download at https://github.com/UDC-GAC/SeQual-Stream .

Light effects on Lasiodiplodia theobromae metabolome cultured in vitro.

INTRODUCTION: The present work identified and compared intracellular metabolites and metabolic networks in mycelial cultures of Lasiodiplodia theobromae grown under 12 natural light and 24 hours' dark using a 1 H NMR-based metabolomics approach. MATERIALS AND METHODS: Fungal cultures were grown in potato dextrose media, and metabolites were extracted by sonication with sodium phosphate-buffered saline (pH = 6.0, 10% D2O, 0.1 mM TSP) from mycelium samples collected every week over four weeks. RESULTS: Multivariate analyses revealed that the light exposure group showed a positive correlation within beta-hydroxybutyrate, acetoacetate, acetone, betaine, choline, glycerol, and phosphocholine. On the other hand, phenyl acetate, leucine, isoleucine, valine, and tyrosine were positively correlated with dark conditions. Light favored the oxidative degradation of valine, leucine, and isoleucine, leading to the accumulation of choline, phosphocholine, betaine, and ketone bodies (ketogenesis). Ketogenesis, gluconeogenesis, and the biosynthesis of choline, phosphocholine, and betaine, were considered discriminatory routes for light conditions. The light-sensing pathways were interlinked with fungal development, as verified by the increased production of mycelia biomass without fruiting bodies and stress signaling, as demonstrated by the increased production of pigments.

Structural and Morphogenetic Characteristics in Paspalum notatum: Responses to Nitrogen Fertilization, Season, and Genotype.

Understanding leaf generation dynamics, their seasonal changes, and their responses to nitrogen fertilization (NF) is key to improving pasture utilization efficiency. The objectives of this research were to determine structural and morphogenetic variables underlying changes in herbage mass on a set of Paspalum notatum genotypes. Ten P. notatum genotypes were evaluated in experimental plots following a completely randomized block design under a split-plot arrangement for two N-rates during four periods. Increased herbage mass (HM) after N-fertilization was explained by a higher tiller density (TD) (41.8%) and tiller weight (TW) (22.1%). The increment of TW after NF was due to the increase in leaf blade length (LBL) and width (LBW). During the flowering season, NF increases the reproductive tiller density by 262.5%. Seasonal variation in HM was mainly explained by changes in LBL that modified TW. Morphogenetic traits differed between genotypes of different growth habits; therefore, different management practices are suggested. The average increase in leaf elongation rate in response to NF was about 36.7%, generating longer leaves despite reductions in leaf elongation time (LET). The depletion in LBL and consequently in TW and HM during the autumn was attributed to the reduction in LET.

Ebselen and Diphenyl Diselenide Inhibit SARS-CoV-2 Replication at Non-Toxic Concentrations to Human Cell Lines.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the causative agent of the COVID-19 pandemic, a global public health problem. Despite the numerous studies for drug repurposing, there are only two FDA-approved antiviral agents (Remdesivir and Nirmatrelvir) for non-hospitalized patients with mild-to-moderate COVID-19 symptoms. Consequently, it is pivotal to search for new molecules with anti-SARS-CoV-2 activity and to study their effects in the human immune system. Ebselen (Eb) is an organoselenium compound that is safe for humans and has antioxidant, anti-inflammatory, and antimicrobial properties. Diphenyl diselenide ((PhSe)2) shares several pharmacological properties with Eb and is of low toxicity to mammals. Herein, we investigated Eb and (PhSe)2 anti-SARS-CoV-2 activity in a human pneumocytes cell model (Calu-3) and analyzed their toxic effects on human peripheral blood mononuclear cells (PBMCs). Both compounds significantly inhibited the SARS-CoV-2 replication in Calu-3 cells. The EC50 values for Eb and (PhSe)2 after 24 h post-infection (hpi) were 3.8 µM and 3.9 µM, respectively, and after 48 hpi were 2.6 µM and 3.4 µM. These concentrations are safe for non-infected cells, since the CC50 values found for Eb and (PhSe)2 on Calu-3 were greater than 200 µM. Importantly, the concentration rates tested on viral replication were not toxic to human PBMCs. Therefore, our findings reinforce the efficacy of Eb and demonstrate (PhSe)2 as a new candidate to be tested in future trials against SARS-CoV-2 infection/inflammation conditions.

Characterizing the information transmission of inverse stochastic resonance and noise-induced activity amplification in neuronal systems.

Purkinje cells exhibit a reduction of the mean firing rate at intermediate-noise intensities, which is somewhat reminiscent of the response enhancement known as "stochastic resonance" (SR). Although the comparison with the stochastic resonance ends here, the current phenomenon has been given the name "inverse stochastic resonance" (ISR). Recent research has demonstrated that the ISR effect, like its close relative "nonstandard SR" [or, more correctly, noise-induced activity amplification (NIAA)], has been shown to stem from the weak-noise quenching of the initial distribution, in bistable regimes where the metastable state has a larger attraction basin than the global minimum. To understand the underlying mechanism of the ISR and NIAA phenomena, we study the probability distribution function of a one-dimensional system subjected to a bistable potential that has the property of symmetry, i.e., if we change the sign of one of its parameters, we can obtain both phenomena with the same properties in the depth of the wells and the width of their basins of attraction subjected to Gaussian white noise with variable intensity. Previous work has shown that one can theoretically determine the probability distribution function using the convex sum between the behavior at small and high noise intensities. To determine the probability distribution function more precisely, we resort to the "weighted ensemble Brownian dynamics simulation" model, which provides an accurate estimate of the probability distribution function for both low and high noise intensities and, most importantly, for the transition of both behaviors. In this way, on the one hand, we show that both phenomena emerge from a metastable system where, in the case of ISR, the global minimum of the system is in a state of lower activity, while in the case of NIAA, the global minimum is in a state of increased activity, the importance of which does not depend on the width of the basins of attraction. On the other hand, we see that quantifiers such as Fisher information, statistical complexity, and especially Shannon entropy fail to distinguish them, but they show the existence of the mentioned phenomena. Thus, noise management may well be a mechanism by which Purkinje cells find an efficient way to transmit information in the cerebral cortex.