Investigating egocentric tuning in hippocampal CA1 neurons.

Navigation requires integrating sensory information with a stable schema to create a dynamic map of an animal's position using egocentric and allocentric coordinate systems. In the hippocampus, place cells encode allocentric space, but their firing rates may also exhibit directional tuning within egocentric or allocentric reference frames. We compared experimental and simulated data to assess the prevalence of tuning to egocentric bearing (EB) among hippocampal cells in rats foraging in an open field. Using established procedures, we confirmed egocentric modulation of place cell activity in recorded data; however, simulated data revealed a high false positive rate. When we accounted for false positives by comparing with shuffled data that retain correlations between the animal's direction and position, only a very low number of hippocampal neurons appeared modulated by EB. Our study highlights biases affecting false positive rates and provides insights into the challenges of identifying egocentric modulation in hippocampal neurons.Significance Statement This study investigates the relationship between world-centered (allocentric) and self-centered (egocentric) frames of spatial coding in the hippocampus during navigation. Through targeted electrophysiological single-unit recordings in hippocampal CA1 area, complemented by simulations of spatially modulated neurons, we find a compelling lack of support in free-foraging rats for recent proposals that the hippocampus relies on internal egocentric signals in relation to reference points distributed through the environment. Our work reveals that ego-centric signals in CA1 may be strongly biased by stereotypical behavioral patterns. The findings suggest that in free-foraging rodents, the principal framework for location coding is allocentric.

Children and adolescents with primary headaches exhibit altered sensory profiles - a multi-modal investigation.

BACKGROUND: Pediatric headache is an increasing medical problem that has adverse effects on children's quality of life, academic performance, and social functioning. Children with primary headaches exhibit enhanced sensory sensitivity compared to their healthy peers. However, comprehensive investigations including multimodal sensory sensitivity assessment are lacking. This study aimed to compare sensory sensitivity of children with primary headaches with their healthy peers across multiple sensory domains. METHODS: The study included 172 participants aged 6 to 17 years (M = 13.09, SD = 3.02 years; 120 girls). Of these 80 participants were patients with migraine, 23 were patients with tension-type headache, and 69 were healthy controls. The following sensory measures were obtained: Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), detection and pain threshold for Transcutaneous Electrical Nerve Stimulation (TENS), olfactory and intranasal trigeminal detection threshold, and odor identification ability. Sensory sensitivity was compared between groups with a series of Kruskal-Wallis tests. Binomial regression models were used to compare the relative utility of sensory sensitivity measures in classifying participants into patients and healthy controls, as well as into patients with migraine and tension-type headache. RESULTS: Patients with migraine had lower MPT measured at the forearm than patients with tension-type headaches and healthy controls. MPS was higher in patients with migraine than in healthy controls. All patients with headaches had lower detection threshold of TENS and higher olfactory sensitivity. Healthy controls showed increased intranasal trigeminal sensitivity. Scores in MPS, TENS, and olfactory and trigeminal thresholds were significantly predicting presence of primary headaches. Additionally, scores in MPT, olfactory and trigeminal threshold were positive predictors of type of headache. CONCLUSIONS: Children with primary headaches exhibit different sensory profiles than healthy controls. The obtained results suggest presence of increased overall, multimodal sensitivity in children with primary headaches, what may negatively impact daily functioning and contribute to further pain chronification. TRIAL REGISTRATION: The study was registered in the German Registry of Clinical Trials (DRKS) DRKS00021062.

Computational NMR Study of Benzothienoquinoline Heterohelicenes.

Early NMR studies of several heterohelicenes containing an annular nitrogen atom and a thiophene ring in their structure suggested the possibility of the lengthening of the carbon-carbon bonds in the interior of the helical turn of the molecule based on the progressive upfield shift of 13C resonances toward the center of the helical turn. We now report a comprehensive analysis of the optimized geometry and a comparison of the calculated vs. observed 1H and 13C NMR chemical shifts of nineteen representative benzothienoquinoline heterohelicenes. As was initially hypothesized on the basis of the progressive upfield shift of carbon resonances toward the center of the interior helical turn, the present computational study has demonstrated that carbon-carbon bonds indeed have more sp3 character and are longer than normal sp2 bonds to accommodate the helical twist of the molecule, as expected.

Sulfated Polyhydroxysteroid Glycosides from the Sea of Okhotsk Starfish Henricia leviuscula spiculifera and Potential Mechanisms for Their Observed Anti-Cancer Activity against Several Types of Human Cancer Cells.

Three new monosulfated polyhydroxysteroid glycosides, spiculiferosides A (1), B (2), and C (3), along with new related unsulfated monoglycoside, spiculiferoside D (4), were isolated from an ethanolic extract of the starfish Henricia leviuscula spiculifera collected in the Sea of Okhotsk. Compounds 1-3 contain two carbohydrate moieties, one of which is attached to C-3 of the steroid tetracyclic core, whereas another is located at C-24 of the side chain of aglycon. Two glycosides (2, 3) are biosides, and one glycoside (1), unlike them, includes three monosaccharide residues. Such type triosides are a rare group of polar steroids of sea stars. In addition, the 5-substituted 3-OSO3-α-L-Araf unit was found in steroid glycosides from starfish for the first time. Cell viability analysis showed that 1-3 (at concentrations up to 100 µM) had negligible cytotoxicity against human embryonic kidney HEK293, melanoma SK-MEL-28, breast cancer MDA-MB-231, and colorectal carcinoma HCT 116 cells. These compounds significantly inhibited proliferation and colony formation in HCT 116 cells at non-toxic concentrations, with compound 3 having the greatest effect. Compound 3 exerted anti-proliferative effects on HCT 116 cells through the induction of dose-dependent cell cycle arrest at the G2/M phase, regulation of expression of cell cycle proteins CDK2, CDK4, cyclin D1, p21, and inhibition of phosphorylation of protein kinases c-Raf, MEK1/2, ERK1/2 of the MAPK/ERK1/2 pathway.

RGD Density on Tadpole Nanostructures Regulates Cancer Stem Cell Proliferation and Stemness.

Cancer stem cells (CSCs) make up a small population of cancer cells, primarily responsible for tumor initiation, metastasis, and drug resistance. They overexpress Arg-Gly-Asp (RGD) binding integrin receptors that play crucial roles in cell proliferation and stemness through interaction with the extracellular matrix. Here, we showed that monodisperse polymeric tadpole nanoparticles covalently coupled with different RGD densities regulated colon CSC proliferation and stemness in a RGD density-dependent manner. These tadpoles penetrated deeply and evenly into tumor spheroids and specifically entered cells with cancer stem markers CD24 and CD133. Low RGD density tadpoles triggered integrin α5 expression that further activated TGF-ß3 and TGF-ß2 signaling pathways, confirmed by the increase of pERK and Bcl-2 protein levels. This process is associated with the RGD cluster presentation controlled by the RGD density on the tadpole surface.

Cholinergic Stimulation Exerts Cardioprotective Effects and Alleviates Renal Inflammatory Responses after Acute Myocardial Infarction in Spontaneous Hypertensive Rats (SHRs).

BACKGROUND: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). METHODS: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. RESULTS: Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury. CONCLUSIONS: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Olfactory function after mild traumatic brain injury in children-a longitudinal case control study.

The prevalence of posttraumatic olfactory dysfunction in children after mild traumatic brain injury ranges from 3 to 58%, with potential factors influencing this variation, including traumatic brain injury severity and assessment methods. This prospective longitudinal study examines the association between mild traumatic brain injury and olfactory dysfunction in children. Seventy-five pediatric patients with mild traumatic brain injury and an age-matched healthy control group were enrolled. Olfactory function was assessed using the Sniffin' Sticks battery, which focuses on olfactory threshold and odor identification. The study found that children with mild traumatic brain injury had impaired olfactory function compared with healthy controls, particularly in olfactory threshold scores. The prevalence of olfactory dysfunction in the patient group was 33% and persisted for 1 yr. No significant association was found between traumatic brain injury symptoms (e.g. amnesia, loss of consciousness) and olfactory dysfunction. The study highlights the importance of assessing olfactory function in children after mild traumatic brain injury, given its potential impact on daily life. Although most olfactory dysfunction appears transient, long-term follow-up is essential to fully understand the recovery process. The findings add valuable insights to the limited literature on this topic and urge the inclusion of olfactory assessments in the management of pediatric mild traumatic brain injury.

The Catalytic Activity of Human REV1 on Undamaged and Damaged DNA.

Eukaryotic REV1 serves as a scaffold protein for the coordination of DNA polymerases during DNA translesion synthesis. Besides this structural role, REV1 is a Y-family DNA polymerase with its own distributive deoxycytidyl transferase activity. However, data about the accuracy and efficiency of DNA synthesis by REV1 in the literature are contrasting. Here, we expressed and purified the full-length human REV1 from Saccharomyces cerevisiae and characterized its activity on undamaged DNA and a wide range of damaged DNA templates. We demonstrated that REV1 carried out accurate synthesis opposite 8-oxoG and O6-meG with moderate efficiency. It also replicated thymine glycol surprisingly well in an error-prone manner, but was blocked by the intrastrand 1,2-GG cisplatin crosslink. By using the 1,N6-ethenoadenine and 7-deaza-adenine lesions, we have provided biochemical evidence of the importance for REV1 functioning of the Hoogsteen face of template A, the second preferable template after G.

A Study on the Impact of the COVID-19 Pandemic on the Aetiology of Paediatric Olfactory Dysfunction.

INTRODUCTION: Although previous studies have examined olfactory dysfunction in children, the novel coronavirus SARS-CoV-2 has certainly had an unprecedented effect on their olfaction, which could not be taken into consideration. The aim of this report was to present data on the epidemiology of olfactory dysfunction during the pandemic and compare this dataset with a pre-pandemic set. We hypothesized an increase in URTI-related olfactory dysfunction. METHODS: Data of paediatric patients consulting a smell and taste clinic between March 2020 and June 2022 were retrospectively analysed. The frequency of major causes of olfactory dysfunction was examined and compared with three subsets of an older dataset. RESULTS: A total of 52 patients were included in the analysis. Most children presented with olfactory dysfunction due to upper respiratory tract infection (URTI) (52%). Congenital olfactory dysfunction was present in 34% of cases. Sinonasal disorders and idiopathic cases accounted for 6 and 4%, respectively, whereas head trauma was the least common cause (2%). This was in contrast with the results of the older set. The frequency of URTI-related olfactory dysfunction increased significantly. The frequency of head-trauma-related or congenital olfactory dysfunction showed marked reductions. There were no significant differences regarding the other aetiologies between our patient cohort and the three subsets. CONCLUSION: The COVID-19 pandemic has resulted in differences regarding the prevalence of aetiologies between our dataset and the subsets of pre-pandemic times. The surge of the frequency of URTI-related olfactory dysfunction may be ascribed to a novel pathomechanism involving sustentacular cells in the olfactory epithelium.

Electrical stimulation of the dorsal motor nucleus of the vagus in male mice can regulate inflammation without affecting the heart rate.

BACKGROUND: The vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN), as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications. However, the anti-inflammatory effectiveness of electrical stimulation of the DMN (eDMNS) and the possible heart rate (HR) alterations associated with this approach have not been investigated. Here, we examined the effects of eDMNS on HR and cytokine levels in mice administered with lipopolysaccharide (LPS, endotoxin) and in mice subjected to cecal ligation and puncture (CLP) sepsis. METHODS: Anesthetized male 8-10-week-old C57BL/6 mice on a stereotaxic frame were subjected to eDMNS using a concentric bipolar electrode inserted into the left or right DMN or sham stimulation. eDMNS (500, 250 or 50 µA at 30 Hz, for 1 min) was performed and HR recorded. In endotoxemia experiments, sham or eDMNS utilizing 250 µA or 50 µA was performed for 5 mins and was followed by LPS (0.5 mg/kg) i.p. administration. eDMNS was also applied in mice with cervical unilateral vagotomy or sham operation. In CLP experiments sham or left eDMNS was performed immediately post CLP. Cytokines and corticosterone were analyzed 90 mins after LPS administration or 24 h after CLP. CLP survival was monitored for 14 days. RESULTS: Either left or right eDMNS at 500 µA and 250 µA decreased HR, compared with baseline pre-stimulation. This effect was not observed at 50 µA. Left side eDMNS at 50 µA, compared with sham stimulation, significantly decreased serum and splenic levels of the pro-inflammatory cytokine TNF and increased serum levels of the anti-inflammatory cytokine IL-10 during endotoxemia. The anti-inflammatory effect of eDMNS was abrogated in mice with unilateral vagotomy and was not associated with serum corticosterone alterations. Right side eDMNS in endotoxemic mice suppressed serum TNF and increased serum IL-10 levels but had no effects on splenic cytokines. In mice with CLP, left side eDMNS suppressed serum IL-6, as well as splenic IL-6 and increased splenic IL-10 and significantly improved the survival rate of CLP mice. CONCLUSIONS: For the first time we show that a regimen of eDMNS which does not cause bradycardia alleviates LPS-induced inflammation. These eDMNS anti-inflammatory effects require an intact vagus nerve and are not associated with corticosteroid alterations. eDMNS also decreases inflammation and improves survival in a model of polymicrobial sepsis. These findings are of interest for further studies exploring bioelectronic anti-inflammatory approaches targeting the brainstem DMN.

Renal implications of coronavirus disease 2019: insights into viral tropism and clinical outcomes.

In recent years, multiple coronaviruses have emerged, with the latest one, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing a global pandemic. Besides respiratory symptoms, some patients experienced extrapulmonary effects, such as cardiac damage or renal injury, indicating the broad tropism of SARS-CoV-2. The ability of the virus to effectively invade the renal cellular environment can eventually cause tissue-specific damage and disease. Indeed, patients with severe coronavirus disease 2019 exhibited a variety of symptoms such as acute proximal tubular injury, ischemic collapse, and severe acute tubular necrosis resulting in irreversible kidney failure. This review summarizes the current knowledge on how it is believed that SARS-CoV-2 influences the renal environment and induces kidney disease, as well as current therapy approaches.

Nb2O5 Microcolumns for Ethanol Sensing.

Pseudohexagonal Nb2O5 microcolumns spanning a size range of 50 to 610 nm were synthesized utilizing a cost-effective hydrothermal process (maintained at 180 °C for 30 min), followed by a subsequent calcination step at 500 °C for 3 h. Raman spectroscopy analysis unveiled three distinct reflection peaks at 220.04 cm-1, 602.01 cm-1, and 735.3 cm-1, indicative of the pseudohexagonal crystal lattice of Nb2O5. The HRTEM characterization confirmed the inter-lattice distance of 1.8 Å for the 110 plain and 3.17 Å for the 100 plain. The conductometry sensors were fabricated by drop-casting a dispersion of Nb2O5 microcolumns, in ethanol, on Pt electrodes. The fabricated sensors exhibited excellent selectivity in detecting C2H5OH (ΔG/G = 2.51 for 10 ppm C2H5OH) when compared to a variety of tested gases, including CO, CO2, NO2, H2, H2S, and C3H6O. The optimal operating temperature for this selective detection was determined to be 500 °C in a dry air environment. Moreover, the sensors demonstrated exceptional repeatability over the course of three testing cycles and displayed strong humidity resistance, even when exposed to 90% relative humidity. This excellent humidity resistance gas sensing property can be attributed to their nanoporous nature and elevated operating temperature.

Prediction of Metal-Organic Frameworks with Phase Transition via Machine Learning.

Metal-organic frameworks (MOFs) possess a virtually unlimited number of potential structures. Although the latter enables an efficient route to control the structure-related functional properties of MOFs, it still complicates the prediction and searching for an optimal structure for specific application. Next to prediction of the MOFs for gas sorption/separation and catalysis via machine learning (ML), we report on ML to find MOFs demonstrating a phase transition (PT). On the basis of an available QMOF database (7463 frameworks), we create and train the autoencoder followed by training the classifier of MOFs from a unique database with experimentally confirmed PT. This makes it possible to identify MOFs with a high potential for PT and evaluate the most likely stimulus for it (guest molecules or temperature/pressure). The formed list of available MOFs for PT allows us to discuss their structural features and opens an opportunity to search for phase change MOFs for diverse physical/chemical application.

Stereochemical and Computational NMR Survey of 1,2,3-Triazoles: in Search of the Original Tauto-Conformers.

The conformational analysis of nine functionalized 1,2,3-triazoles was carried out by the correlation of calculated and experimental high-level nuclear magnetic resonance (NMR) chemical shifts. In solution, the studied triazoles are in exchange dynamic equilibrium caused by their prototropic tautomerism of the NH-proton. The experimentally unresolved NMR signals were assigned for most of the compounds. A more thorough survey was conducted for 4-t-butyl-1,2,3-triazole-5-carbaldehyde oxime. The analysis performed within the framework of the DP4+ formalism completely confirmed the hypothesis of the predominance of the 2H-tautomer. Thus, the methodology for estimating stereochemical structures in the absence of some experimental data allowed the most stable conformations for dynamic systems with different tautomeric ratios to be reliably identified.

Acute heart failure - an EFIM guideline critical appraisal and adaptation for internists.

BACKGROUND: Over the past two decades, several studies have been conducted that have tried to answer questions on management of patients with acute heart failure (AHF) in terms of diagnosis and treatment. Updated international clinical practice guidelines (CPGs) have endorsed the findings of these studies. The aim of this document was to adapt recommendations of existing guidelines to help internists make decisions about specific and complex scenarios related to AHF. METHODS: The adaptation procedure was to identify firstly unresolved clinical problems in patients with AHF in accordance with the PICO (Population, Intervention, Comparison and Outcomes) process, then conduct a critical assessment of existing CPGs and choose recommendations that are most applicable to these specific scenarios. RESULTS: Seven PICOs were identified and CPGs were assessed. There is no single test that can help clinicians in discriminating patients with acute dyspnoea, congestion or hypoxaemia. Performing of echocardiography and natriuretic peptide evaluation is recommended, and chest X-ray and lung ultrasound may be considered. Treatment strategies to manage arterial hypotension and low cardiac output include short-term continuous intravenous inotropic support, vasopressors, renal replacement therapy, and temporary mechanical circulatory support. The most updated recommendations on how to treat specific patients with AHF and certain comorbidities and for reducing post-discharge rehospitalization and mortality are provided. Overall, 51 recommendations were endorsed and the rationale for the selection is provided in the main text. CONCLUSION: Through the use of appropriate tailoring process methodology, this document provides a simple and updated guide for internists dealing with AHF patients.

Smelling of the mothers' diet in amniotic fluid by adult noses.

In this study, the transfer of odorants, namely vanilla, and garlic, into the amniotic fluid (AF) during the second trimester was investigated by examination of collected AF samples through healthy adults. Eleven AF samples were collected from pregnant women (aged 32.9 ±â€…4.9 yr, 16-25 wk of gestation) undergoing diagnostic amniocentesis after eating garlic oil or vanilla powder in high-fat yogurt. The control group did not receive food before amniocentesis. Two vanilla, 3 garlic, and 6 control samples were collected through amniocentesis 60-120 min after ingestion. Samples were collected at -80 °C and carefully defrosted over 12 h at the same time point. Sixteen healthy volunteers (8 males, aged 26.5 ±â€…5.0 yr) were asked to judge AF samples with potential garlic or vanilla odors from controls in a 2-alternative forced choice (2AFC) paradigm. Judges were able to identify vanilla in the AF samples with an estimated probability of 50%, resulting in a significant P-value of < 0.001. In contrast, the identification of garlic was unsuccessful with a P-value of 0.86, and only 2 judges were able to identify both vanilla and garlic. According to the results of this study, the vanilla odor probably passes into the amniotic fluid.

Application of DUT-4 MOF structure switching for optical and electrical humidity sensing.

The threshold structural transformation of the DUT-4 metal-organic framework (MOF) from an ordered to distorted phase during exposure to ambient conditions has been revealed. The in situ X-ray diffraction analysis, in situ Raman and FTIR spectroscopy, scanning electron microscopy and synchronous thermal analysis have been used for investigation. The reversible effect of exposure time and humidity on such a phase transition has been confirmed. We also demonstrated that the observed phase transition correlated well with changes in the optical and electronic properties of DUT-4, paving the way to a new family of MOF-based phase change materials for optoelectronic applications.