-
BioRxiv : the Preprint Server For... Jun 2024The vestibular nerve is comprised of neuron sub-groups with diverse functions related to their intrinsic biophysical properties. This diversity is partly due to...
The vestibular nerve is comprised of neuron sub-groups with diverse functions related to their intrinsic biophysical properties. This diversity is partly due to differences in the types and numbers of low-voltage-gated potassium channels found in the neurons' membranes. Expression for some low-voltage gated ion channels like KCNQ4 is upregulated during early post-natal development; suggesting that ion channel composition and neuronal diversity may be shaped by hair cell activity. This idea is consistent with recent work showing that glutamatergic input from hair cells is necessary for the normal diversification auditory neurons. To test if biophysical diversity is similarly dependent on glutamatergic input in vestibular neurons, we examined the maturation of the vestibular epithelium and ganglion neurons in mice whose hair cell synapses lack glutamate. Despite lacking glutamatergic input, the knockout mice showed no notable balance deficits and crossed challenging balance beams with little difficulty. Immunolabeling of the vestibular epithelia showed normal development as indicated by an identifiable striolar zone with calyceal terminals labeled by molecular marker calretinin, and normal expression of KCNQ4 by the end of the second post-natal week. We found similar numbers of Type I and Type II hair cells in the knockout and wildtype animals, regardless of epithelial zone. Thus, the presumably quiescent Type II hair cells are not cleared from the epithelium. Patch-clamp recordings showed that biophysical diversity of vestibular ganglion neurons in the mice is comparable to that found in wildtype controls, with a similar range firing patterns at both immature and juvenile ages. However, our results suggest a subtle biophysical alteration to the largest ganglion cells (putative somata of central zone afferents); those in the knockout had smaller net conductance and were more excitable than those in the wild type. Thus, unlike in the auditory nerve, glutamatergic signaling is unnecessary for producing biophysical diversity in vestibular ganglion neurons. And yet, because the input signals from vestibular hair cells are complex and not solely reliant on quantal release of glutamate, whether diversity of vestibular ganglion neurons is simply hardwired or regulated by a more complex set of input signals remains to be determined.
PubMed: 38915604
DOI: 10.1101/2024.06.12.597464 -
BioRxiv : the Preprint Server For... Jun 2024Microbes must adapt to diverse biotic and abiotic factors encountered in host environments. Polyamines are an abundant class of aliphatic molecules that play essential...
Microbes must adapt to diverse biotic and abiotic factors encountered in host environments. Polyamines are an abundant class of aliphatic molecules that play essential roles in fundamental cellular processes across the tree of life. Surprisingly, the bacterial pathogen is highly sensitive to polyamines encountered during infection, and acquisition of a polyamine resistance locus has been implicated in spread of the prominent USA300 methicillin-resistant lineage. At present, alternative pathways of polyamine resistance in staphylococci are largely unknown. Here we applied experimental evolution to identify novel mechanisms and consequences of adaption when exposed to increasing concentrations of the polyamine spermine. Evolved populations of exhibited striking evidence of parallel adaptation, accumulating independent mutations in the potassium transporter genes and . Mutations in either or are sufficient to confer polyamine resistance and function in an additive manner. Moreover, we find that ktr mutations provide increased resistance to multiple classes of unrelated cationic antibiotics, suggesting a common mechanism of resistance. Consistent with this hypothesis, ktr mutants exhibit alterations in cell surface charge indicative of reduced affinity and uptake of cationic molecules. Finally, we observe that laboratory-evolved ktr mutations are also present in diverse natural isolates, suggesting these mutations may contribute to antimicrobial resistance during human infections. Collectively this study identifies a new role for potassium transport in polyamine resistance with consequences for susceptibility to both host-derived and clinically-used antimicrobials.
PubMed: 38915543
DOI: 10.1101/2024.06.15.599172 -
BioRxiv : the Preprint Server For... Jun 2024Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high...
UNLABELLED
Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in two B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis.
AUTHOR SUMMARY / SIGNIFICANCE
Viral infections profoundly alter host cell biological programming in ways that potentiate disease. Epstein-Barr virus (EBV) is a particularly prevalent human pathogen associated with diverse cancers and several autoimmune disorders. EBV predominantly establishes latent infection in B cells and can promote B cell malignancies through functions of well-characterized latent oncoproteins. Aspects of the viral lytic cycle also clearly contribute to EBV-associated diseases, although pathologic roles of lytic reactivation are incompletely understood. Here we use single-cell techniques to examine cellular responses to EBV lytic reactivation in multiple B cell models. Consistent with prior studies, reactivation from latency is incomplete (abortive) in some cells and successful in others. Abortive and full lytic trajectories exhibit distinct biological responses that each may promote pathogenesis and reinforce bimodal latent-lytic control. Intriguingly, a portion on cells that proceed through the lytic cycle exhibits unexpected and striking expression of genes associated with cellular reprogramming, pluripotency, and self-renewal. Collectively, this study provides a valuable resource to understand diverse host-virus dynamics and fates during viral reactivation and identifies multiple modes of EBV lytic pathogenesis to investigate in future research.
PubMed: 38915538
DOI: 10.1101/2024.06.14.598975 -
Journal of Pain Research 2024Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The...
PURPOSE
Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The nucleus accumbens (NAc) plays an important role in mediating emotional and cognitive processes and analgesia. This study investigated the resting-state functional connectivity (rsFC) and effective connectivity (EC) of NAc and its subregions in cLBP.
METHODS
Thirty-four cLBP patients and 34 age- and sex-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based rsFC and Dynamic Causal Modelling (DCM) were used to examine the alteration of the rsFC and EC of the NAc.
RESULTS
Our results showed that the cLBP group had increased rsFC of the bilateral NAc-left superior frontal cortex (SFC), orbital frontal cortex (OFC), left angular gyrus, the left NAc-bilateral middle temporal gyrus, as well as decreased rsFC of left NAc-left supramarginal gyrus, right precentral gyrus, left cerebellum, brainstem (medulla oblongata), and right insula pathways compared with the HC; the results of the subregions were largely consistent with the whole NAc. In addition, the rsFC of the left NAc-left SFC was negatively correlated with Hamilton's Depression Scale (HAMD) scores ( = -0.402, = 0.018), and the rsFC of left NAc-OFC was positively correlated with present pain intensity scores ( = 0.406, = 0.017) in the cLBP group. DCM showed that the cLBP group showed significantly increased EC from the left cerebellum to the right NAc ( = 0.012) as compared with HC.
CONCLUSION
Overall, our findings demonstrate aberrant rsFC and EC between NAc and regions that are associated with emotional regulation and cognitive processing in individuals with cLBP, underscoring the pivotal roles of emotion and cognition in cLBP.
PubMed: 38915479
DOI: 10.2147/JPR.S455239 -
Journal of Neuroengineering and... Jun 2024Repeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects,... (Meta-Analysis)
Meta-Analysis Review
Impact of repetitive transcranial magnetic stimulation on cortical activity: a systematic review and meta-analysis utilizing functional near-infrared spectroscopy evaluation.
BACKGROUND
Repeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects, functional near-infrared spectroscopy (fNIRS), an optical neuroimaging modality adept at detecting changes in cortical hemodynamic responses, has been employed concurrently alongside rTMS to measure and tailor the impact of diverse rTMS protocols on the brain cortex.
OBJECTIVE
This systematic review and meta-analysis aimed to elucidate the effects of rTMS on cortical hemodynamic responses over the primary motor cortex (M1) as detected by fNIRS.
METHODS
Original articles that utilized rTMS to stimulate the M1 cortex in combination with fNIRS for the assessment of cortical activity were systematically searched across the PubMed, Embase, and Scopus databases. The search encompassed records from the inception of these databases up until April, 2024. The assessment for risk of bias was also conducted. A meta-analysis was also conducted in studies with extractable raw data.
RESULTS
Among 312 studies, 14 articles were eligible for qualitative review. 7 studies were eligible for meta-analysis. A variety of rTMS protocols was employed on M1 cortex. In inhibitory rTMS, multiple studies observed a reduction in the concentration of oxygenated hemoglobin [HbO] at the ipsilateral M1, contrasted by an elevation at the contralateral M1. Meta-analysis also corroborated this consistent trend. Nevertheless, certain investigations unveiled diminished [HbO] in bilateral M1. Several studies also depicted intricate inhibitory or excitatory interplay among distinct cortical regions.
CONCLUSION
Diverse rTMS protocols led to varied patterns of cortical activity detected by fNIRS. Meta-analysis revealed a trend of increasing [HbO] in the contralateral cortices and decreasing [HbO] in the ipsilateral cortices following low frequency inhibitory rTMS. However, due to the heterogeneity between studies, further research is necessary to comprehensively understand rTMS-induced alterations in brain activity.
Topics: Transcranial Magnetic Stimulation; Spectroscopy, Near-Infrared; Humans; Motor Cortex
PubMed: 38915003
DOI: 10.1186/s12984-024-01407-9 -
BMC Oral Health Jun 2024The aim of the study was to investigate the changes occurring in the mandibular condyle by using mentoplate together with rapid maxillary expansion (MP-RME) treatment in...
BACKGROUND
The aim of the study was to investigate the changes occurring in the mandibular condyle by using mentoplate together with rapid maxillary expansion (MP-RME) treatment in the correction of skeletal class III relationship, using fractal analysis (FA).
METHODS
The sample consisted of 30 individuals (8-11 years) diagnosed with skeletal Class III malocclusion who underwent MP-RME treatment. Archival records provided cone-beam computed tomography (CBCT) images taken at two intervals: before MP-RME treatment (T0) and after treatment (T1). The CBCT images were obtained using standardized settings to ensure consistency in image quality and resolution. The trabecular structures in the bilateral condyles at both T0 and T1 were analyzed using FA. The FA was performed on these condylar images using the Image J software. The region of interest (ROI) was carefully selected in the condyle to avoid overlapping with cortical bone, and the box-counting method was employed to calculate the fractal dimension (FD). Statistical analysis was conducted to compare the FD values between T0 and T1 and to evaluate gender differences. The statistical significance was determined using paired t-tests for intra-group comparisons and independent t-tests for inter-group comparisons, with a significance level set at p < 0.05.
RESULTS
The analysis revealed no statistically significant differences in the trabecular structures of the condyles between T0 and T1 (p > 0.05). However, a significant gender difference was observed in FA values, with males exhibiting higher FA values in the left condyle compared to females at both T0 and T1 (p < 0.05). Specifically, the FA values in the left condyle increased from a mean of 1.09 ± 0.09 at T0 to 1.13 ± 0.08 at T1 in males, whereas in females, the FA values remained relatively stable with a mean of 1 ± 0.09 at T0 and 1.03 ± 0.11 at T1.
CONCLUSION
The findings indicate that MP-RME therapy does not induce significant alterations in the trabecular structure of the mandibular condyle. These results suggest the treatment's safety concerning the structural integrity of the condyle, although the observed gender differences in FA values warrant further investigation.
Topics: Humans; Mandibular Condyle; Malocclusion, Angle Class III; Female; Male; Cone-Beam Computed Tomography; Child; Palatal Expansion Technique; Fractals
PubMed: 38915000
DOI: 10.1186/s12903-024-04506-0 -
Frontiers in Human Neuroscience 2024Repetitive somatosensory stimulation (RSS) is a conventional approach to modulate the neural states of both the primary somatosensory cortex (S1) and the primary motor...
INTRODUCTION
Repetitive somatosensory stimulation (RSS) is a conventional approach to modulate the neural states of both the primary somatosensory cortex (S1) and the primary motor cortex (M1). However, the impact of RSS on skill acquisition and retention in sensorimotor adaptation remains debated. This study aimed to investigate whether whole-hand water flow (WF), a unique RSS-induced M1 disinhibition, influences sensorimotor adaptation by examining the hypothesis that whole-hand WF leads to M1 disinhibition; thereby, enhancing motor memory retention.
METHODS
Sixty-eight young healthy participants were randomly allocated to three groups based on the preconditioning received before motor learning: control, whole-hand water immersion (WI), and whole-hand WF. The experimental protocol for all the participants spanned two consecutive days. On the initial day (day 1), baseline transcranial magnetic stimulation (TMS) assessments (T0) were executed before any preconditioning. Subsequently, each group underwent their respective 30 min preconditioning protocol. To ascertain the influence of each preconditioning on the excitability of the M1, subsequent TMS assessments were conducted (T1). Following this, all participants engaged in the motor learning (ML) of a visuomotor tracking task, wherein they were instructed to align a cursor with a target trajectory by modulating the pinch force. Upon completion of the ML session, final TMS assessments (T2) were conducted. All participants were required to perform the same motor learning 24 h later on day 2.
RESULTS
The results revealed that whole-hand WF did not significantly influence skill acquisition during sensorimotor adaptation, although it did reduce intracortical inhibition. This phenomenon is consistent with the idea that S1, rather than M1, is involved in skill acquisition during the early stages of sensorimotor adaptation. Moreover, memory retention 24 h after skill acquisition did not differ significantly across the three groups, challenging our initial hypothesis that whole-hand WF enhances memory retention throughout sensorimotor adaptation. This could be due to the inability of whole-hand WF to alter sensorimotor connectivity and integration, as well as the nature of the plastic response elicited by the preconditioning.
DISCUSSION
In conclusion, these findings suggest that although whole-hand WF attenuates intracortical inhibition, it does not modulate skill acquisition or motor memory retention during sensorimotor adaptation.
PubMed: 38911224
DOI: 10.3389/fnhum.2024.1398164 -
Veterinary World May 2024Irradiation is one of the most effective microbial decontamination treatments for eliminating foodborne pathogens and enhancing chicken meat safety. The effect of gamma...
BACKGROUND AND AIM
Irradiation is one of the most effective microbial decontamination treatments for eliminating foodborne pathogens and enhancing chicken meat safety. The effect of gamma irradiation on the overall quality of chicken meat and its products must be observed to provide a comprehensive explanation to the public. This meta-analysis examined the effects of gamma irradiation on the oxidation parameters, microbial activity, physicochemical characteristics, sensory parameters, and nutrient quality of chicken meat and meat products.
MATERIALS AND METHODS
We conducted a literature search using various search engines (Scopus®, PubMed®, and Google Scholar®) with "irradiation," "gamma," "chicken," and "meat" as keywords. Gamma irradiation treatment was set as a fixed effect, and the difference between experiments was set as a random effect. This study used a mixed-model methodology. After evaluation, we selected 43 articles (86 studies) for inclusion in the database.
RESULTS
Gamma irradiation significantly increased (p < 0.01) thiobarbituric acid-reactive substance levels on days 0, 7, and 14 of storage. Gamma irradiation reduced total aerobic bacteria, coliforms, , yeast, and mold activity (p < 0.01). According to our meta-analysis, 21.75 kGy was the best dose for reducing total aerobic bacteria. On day 0, gamma irradiation did not affect the color parameters (, , ). However, a significant difference (p < 0.01) was noted for and parameters between the control and irradiation treatments at 7 and 14 days. Although irradiation treatment was less consistent in sensory parameters, overall acceptability decreased on days 0, 7, and 14 after storage (p < 0.05). Regarding nutrient composition, gamma irradiation reduced moisture content and free fatty acid (FFA) content (p < 0.05). Although irradiation significantly reduces the microbial population, it increases the oxidation of chicken meat and its products. Irradiation decreases FFA content and overall acceptability, but it does not affect flavor, tenderness, juiciness, or cooking loss.
CONCLUSION
Gamma irradiation positively reduces the microbial activity in chicken meat and its products but increases the oxidation parameters. Although gamma irradiation does not alter the flavor, tenderness, juiciness, or cooking loss, gamma irradiation can reduce the FFA content and overall acceptability.
PubMed: 38911085
DOI: 10.14202/vetworld.2024.1084-1097 -
Current Research in Immunology 2024Lymphoblastoid cell lines (LCLs) are immortalised peripheral B lymphocytes, transformed via infection with Epstein Barr virus (EBV). The use of LCLs to study B cell...
Lymphoblastoid cell lines (LCLs) are immortalised peripheral B lymphocytes, transformed via infection with Epstein Barr virus (EBV). The use of LCLs to study B cell function remains controversial and core markers to define physiological B cell populations are not consistent between studies of physiological B cells and LCLs. A consensus on the nature of these commonly used cell lines has not been reached. Recently, a core set of markers to subtype peripheral B cells was proposed, addressing the lack of agreed markers for B cell characterisation. In this present study, the consensus panel was applied to describe the B cell subtypes in LCLs. We found that LCLs were generally not physiologically representative of B cells, with most cells harbouring marker combinations absent on peripheral B cells. Some B cell subtyping markers were fundamentally altered during EBV transformation to LCLs (e.g. CD19, CD21). Notably, most LCLs secreted IgG but the associated marker combinations were predominantly only present following EBV transformation. This study therefore informs interpretation of past investigations, and planning of future studies using LCLs, as these cells are unlikely to behave like their pre-transformed B cell subtype.
PubMed: 38910966
DOI: 10.1016/j.crimmu.2024.100079 -
The Korean Journal of Internal Medicine Jun 2024Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the...
BACKGROUND/AIMS
Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the effect of thyroid-stimulating hormone (TSH) levels on CPK levels after statin administration. Therefore, this study aimed to investigate CPK level alterations after statin administration according to TSH quartiles in participants with euthyroidism.
METHODS
This retrospective analysis included 25,047 patients with euthyroidism. CPK levels were measured before and 6 months after statin administration. Normal TSH levels were divided into four quartiles, and the CPK levels and proportions of patients with normal CPK levels after statin administration for each TSH quartile were evaluated.
RESULTS
The baseline CPK level was significantly higher in the lowest TSH quartile (Q1) compared to the other quartiles but decreased after statin administration. Thus, the difference between the CPK levels and the other quartile groups was not significant. The proportion of patients with normal CPK levels was also significantly lowest in Q1 before statin administration; however, no significant difference was noted in the ratio among each group after statin administration. These findings were consistent with the findings of the analysis according to statin intensity.
CONCLUSIONS
In patients in the lowest TSH quartile of the normal TSH range, the CPK level decreased, and the proportion of normal CPK levels increased significantly after statin administration. However, similar changes were not observed in other TSH quartiles. Therefore, further studies are required to mechanistically confirm these conclusions.
PubMed: 38910508
DOI: 10.3904/kjim.2024.085