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The Journal of Cell Biology Oct 2024Regulated cell shape change requires the induction of cortical cytoskeletal domains. Often, local changes to plasma membrane (PM) topography are involved. Centrosomes...
Regulated cell shape change requires the induction of cortical cytoskeletal domains. Often, local changes to plasma membrane (PM) topography are involved. Centrosomes organize cortical domains and can affect PM topography by locally pulling the PM inward. Are these centrosome effects coupled? At the syncytial Drosophila embryo cortex, centrosome-induced actin caps grow into dome-like compartments for mitoses. We found the nascent cap to be a collection of PM folds and tubules formed over the astral centrosomal MT array. The localized infoldings require centrosome and dynein activities, and myosin-based surface tension prevents them elsewhere. Centrosome-engaged PM infoldings become specifically enriched with an Arp2/3 induction pathway. Arp2/3 actin network growth between the infoldings counterbalances centrosomal pulling forces and disperses the folds for actin cap expansion. Abnormal domain topography with either centrosome or Arp2/3 disruption correlates with decreased exocytic vesicle association. Together, our data implicate centrosome-organized PM infoldings in coordinating Arp2/3 network growth and exocytosis for cortical domain assembly.
Topics: Animals; Actin-Related Protein 2-3 Complex; Actins; Cell Membrane; Centrosome; Drosophila melanogaster; Drosophila Proteins; Dyneins; Exocytosis; Microtubules
PubMed: 38935075
DOI: 10.1083/jcb.202403115 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that...
In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that obesogenic high-fat and sugar diet intake during adolescence (adoHFSD) impairs hippocampus (HPC)-dependent memory in rodents. These results were obtained in males only and it remains to evaluate whether adoHFSD has similar effect in females. Therefore, here, we investigated the effects of adoHFSD consumption on HPC-dependent contextual fear memory and associated brain activation in male and female mice. Exposure to adoHFSD increased fat mass accumulation and glucose levels in both males and females but impaired contextual fear memory only in males. Compared with females, contextual fear conditioning induced higher neuronal activation in the dorsal and ventral HPC (CA1 and CA3 subfields) as well as in the medial prefrontal cortex in males. Also, adoHFSD-fed males showed enhanced c-Fos expression in the dorsal HPC, particularly in the dentate gyrus, and in the basolateral amygdala compared with the other groups. Finally, chemogenetic inactivation of the dorsal HPC rescued adoHFSD-induced memory deficits in males. Our results suggest that males are more vulnerable to the effects of adoHFSD on HPC-dependent aversive memory than females, due to overactivation of the dorsal HPC.
Topics: Animals; Fear; Male; Female; Hippocampus; Diet, High-Fat; Obesity; Sex Characteristics; Mice; Memory; Mice, Inbred C57BL; Prefrontal Cortex
PubMed: 38934712
DOI: 10.1093/cercor/bhae254 -
Advances in Clinical and Experimental... Jun 2024Diabetic foot ulcers (DFUs) represent one of the most severe late-stage complications of diabetes. Tibial cortex transverse transport (TTT) surgery stands as the...
Correlation analysis of patients with diabetic foot ulcers treated with tibial cortex transverse transport surgery and platelet-to-lymphocyte ratio and monocyte-to-neutrophil ratio.
BACKGROUND
Diabetic foot ulcers (DFUs) represent one of the most severe late-stage complications of diabetes. Tibial cortex transverse transport (TTT) surgery stands as the prevailing method for addressing DFUs. This surgical intervention holds the promise of expediting DFU wound healing and diminishing the rate of amputations, with the mitigation of inflammatory responses playing a pivotal role. In this study, we aim to explore the correlation between inflammation and TTT surgery, with the overarching goal of facilitating swift prognostic assessments in clinical practice.
OBJECTIVES
The correlation between the severity of DFUs and clinical test results remains ambiguous. A clinical prediction model was devised to explore the connection between DFU severity and the efficacy of TTT surgery, utilizing straightforward and efficient clinical indicators.
MATERIAL AND METHODS
Clinical data and examination results were gathered by tracking hospitalized DFU patients who underwent TTT surgery at the First Affiliated Hospital of Guangxi Medical University (Nanning, China). Indicators associated with DFU severity and wound healing time post-surgery were identified through logistic regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Subsequently, a clinical prediction model was constructed. Finally, the intersection of these 2 sets of indicators revealed factors correlated with wound severity and post-operative healing duration.
RESULTS
Our study was comprised of 202 patients who were categorized into 2 groups based on Wagner's grading classifications. Utilizing Student's t-tests, LASSO regression and logistic regression analyses, we identified 3 factors indicative of DFU severity: platelet-to-lymphocyte ratio (PLR), mixed lymphocyte reaction (MLR) and hemoglobin (HGB). Univariate COX regression analysis revealed 12 factors such as: white blood cells (WBC), neutrophils (NEUT), monocytes (MO), PLR, MLR, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), age, lymphocytes (LY), monocyte-to-neutrophil ratio (MNR), uric acid (UA), and albumin (ALB) associated with the postoperative healing duration. Ultimately, we identified 2 factors, PLR and MNR, at the intersection of these 2 datasets.
CONCLUSIONS
Platelet-to-lymphocyte ratio and MNR were identified as factors associated with both the severity of DFUs and the prognosis following TTT surgery.
PubMed: 38934335
DOI: 10.17219/acem/187765 -
Frontiers in Neuroanatomy 2024A new analysis is presented of the retrograde tracer measurements of connections between anatomical areas of the marmoset cortex. The original normalisation of raw data...
A new analysis is presented of the retrograde tracer measurements of connections between anatomical areas of the marmoset cortex. The original normalisation of raw data yields the fractional link weight measure, FLNe. That is re-examined to consider other possible measures that reveal the underlying in link weights. Predictions arising from both are used to examine network modules and hubs. With inclusion of the in weights the InfoMap algorithm identifies eight structural modules in marmoset cortex. In and out hubs and major connector nodes are identified using module assignment and participation coefficients. Time evolving network tracing around the major hubs reveals medium sized clusters in pFC, temporal, auditory and visual areas; the most tightly coupled and significant of which is in the pFC. A complementary viewpoint is provided by examining the highest traffic links in the cortical network, and reveals parallel sensory flows to pFC and via association areas to frontal areas.
PubMed: 38933918
DOI: 10.3389/fnana.2024.1403170 -
Cureus May 2024Background Motivation dysregulation is common in several psychiatric disorders. However, little is known about the relationships between motivation and the regional...
Background Motivation dysregulation is common in several psychiatric disorders. However, little is known about the relationships between motivation and the regional brain areas involved. We evaluated the relationships between brain microstructural features and causality orientation in patients with schizophrenia, major depressive disorder (MDD), and bipolar disorder (BD) using diffusional kurtosis imaging (DKI) techniques. Methods Forty patients with MDD, 36 with BD, and 30 with schizophrenia underwent DKI and assessment using the General Causality Orientation Scale (GCOS). We analyzed the DKI index and the GCOS subscales. Results The psychiatric patients showed significant positive correlations between the GCOS-autonomy orientation score and the mean kurtosis (MK) values in the prefrontal regions, orbitofrontal regions, and posterior cingulate cortex. When the analyses were performed separately by disease and gender, a positive correlation was found between the GCOS-autonomy orientation score and the MK values in the left prefrontal regions transdiagnostically, especially among female patients with MDD, BD, and schizophrenia. Conclusions A similar association between intrinsic motivation and MK value in the left prefrontal cortex was suggested in patients with schizophrenia, MDD, and BD. The commonality of this association among these disorders might lead to the discovery of a new biomarker for psychiatric clinical research.
PubMed: 38933632
DOI: 10.7759/cureus.61138 -
Neurobiology of Stress Jul 2024High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS)...
High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS) disruptions. However, neural mechanisms underlying drinking behaviors associated with stress and ANS disruptions remain unclear. The current study aims to understand neural correlates of stress, ANS disruptions, and subsequent alcohol intake in social drinkers with risky drinking. Using functional magnetic resonance imaging (fMRI), we investigated brain and heart rate (HR) autonomic responses during brief exposure to stress, alcohol, and neutral cues utilizing a well-validated, individualized imagery paradigm in 48 social drinkers of which 26 reported high-risk drinking (HD) while 22 reported low-risk drinking (LD) patterns. Results indicated that HD individuals showed stress and ANS disruptions with increased basal HR, stress-induced craving, and decreased brain response to stress exposure in frontal-striatal regions including the ventromedial prefrontal cortex (VmPFC), anterior cingulate cortex, striatum, insula, and temporal gyrus. Furthermore, whole-brain correlation analysis indicated that greater basal HR was associated with hypoactive VmPFC, but hyperactive medulla oblongata (MOb) responses during stress, with an inverse association between activity in the VmPFC and Mob (whole-brain corrected (WBC), p < 0.05). Functional connectivity with the MOb as a seed to the whole brain indicated that HD versus LD had decreased functional connectivity between the VmPFC and MOb during stress (WBC, p < 0.05). In addition, those with more compromised functional connectivity between the VmPFC and MOb during stress consumed greater amount of alcohol beverage during an experimental alcohol taste test conducted on a separate day, as well as in their self-reported weekly alcohol intake. Together, these results indicate that stress-related, dysfunctional VmPFC control over brain regions of autonomic arousal contributes to greater alcohol motivation and may be a significant risk factor for hazardous alcohol use in non-dependent social drinkers. Findings also suggest that restoring VmPFC integrity in modulating autonomic arousal during stress may be critical for preventing the development of AUD.
PubMed: 38933283
DOI: 10.1016/j.ynstr.2024.100645 -
Frontiers in Robotics and AI 2024We recently introduced a frameless, navigated, robot-driven laser tool for depth electrode implantation as an alternative to frame-based procedures. This method has...
We recently introduced a frameless, navigated, robot-driven laser tool for depth electrode implantation as an alternative to frame-based procedures. This method has only been used in cadaver and non-recovery studies. This is the first study to test the robot-driven laser tool in an recovery animal study. A preoperative computed tomography (CT) scan was conducted to plan trajectories in sheep specimens. Burr hole craniotomies were performed using a frameless, navigated, robot-driven laser tool. Depth electrodes were implanted after cut-through detection was confirmed. The electrodes were cut at the skin level postoperatively. Postoperative imaging was performed to verify accuracy. Histopathological analysis was performed on the bone, dura, and cortex samples. Fourteen depth electrodes were implanted in two sheep specimens. Anesthetic protocols did not show any intraoperative irregularities. One sheep was euthanized on the same day of the procedure while the other sheep remained alive for 1 week without neurological deficits. Postoperative MRI and CT showed no intracerebral bleeding, infarction, or unintended damage. The average bone thickness was 6.2 mm (range 4.1-8.0 mm). The angulation of the planned trajectories varied from 65.5° to 87.4°. The deviation of the entry point performed by the frameless laser beam ranged from 0.27 mm to 2.24 mm. The histopathological analysis did not reveal any damage associated with the laser beam. The novel robot-driven laser craniotomy tool showed promising results in this first recovery study. These findings indicate that laser craniotomies can be performed safely and that cut-through detection is reliable.
PubMed: 38933084
DOI: 10.3389/frobt.2024.1355409 -
Clinical and Translational Science Jun 2024Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of...
Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1 miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology. The prefrontal lobe, anterior cingulate, and hippocampus from NF1 and wild-type miniswine were examined longitudinally, revealing abnormalities in mature oligodendrocytes and astrocytes, and microglial activation over time. Imbalances in GABA: Glutamate ratios and GAD67 expression were observed in the hippocampus and motor cortex, supporting the role of disruption in inhibitory neurotransmission in NF1 cognitive impairment and motor dysfunction. Moreover, NF1 miniswine demonstrated slower and shorter steps, indicative of a balance-preserving response commonly observed in NF1 patients, and progressive memory and learning impairments. Collectively, our findings affirm the effectiveness of NF1 miniswine as a valuable resource for assessing cognitive and motor impairments associated with NF1, investigating the involvement of specific neural circuits and glia in these processes, and evaluating potential therapeutic interventions.
Topics: Animals; Neurofibromatosis 1; Disease Models, Animal; Mice; Neurofibromin 1; Behavior, Animal; Male; Hippocampus; Cognitive Dysfunction; Oligodendroglia; Humans; Astrocytes; Female
PubMed: 38932491
DOI: 10.1111/cts.13858 -
Pharmaceuticals (Basel, Switzerland) May 2024Fear-related disorders, including post-traumatic stress disorder (PTSD), and anxiety disorders are pervasive psychiatric conditions marked by persistent fear, stemming...
Fear-related disorders, including post-traumatic stress disorder (PTSD), and anxiety disorders are pervasive psychiatric conditions marked by persistent fear, stemming from its dysregulated acquisition and extinction. The primary treatment for these disorders, exposure therapy (ET), relies heavily on fear extinction (FE) principles. Adolescence, a vulnerable period for developing psychiatric disorders, is characterized by neurobiological changes in the fear circuitry, leading to impaired FE and increased susceptibility to relapse following ET. Ketamine, known for relieving anxiety and reducing PTSD symptoms, influences fear-related learning processes and synaptic plasticity across the fear circuitry. Our study aimed to investigate the effects of ketamine (10 mg/kg) on FE in adolescent male C57 BL/6 mice at the behavioral and molecular levels. We analyzed the protein and gene expression of synaptic plasticity markers in the hippocampus (HPC) and prefrontal cortex (PFC) and sought to identify neural correlates associated with ketamine's effects on adolescent extinction learning. Ketamine ameliorated FE in the adolescent males, likely affecting the consolidation and/or recall of extinction memory. Ketamine also increased the Akt and mTOR activity and the GluA1 and GluN2A levels in the HPC and upregulated BDNF exon IV mRNA expression in the HPC and PFC of the fear-extinguished mice. Furthermore, ketamine increased the c-Fos expression in specific brain regions, including the ventral HPC (vHPC) and the left infralimbic ventromedial PFC (IL vmPFC). Providing a comprehensive exploration of ketamine's mechanisms in adolescent FE, our study suggests that ketamine's effects on FE in adolescent males are associated with the activation of hippocampal Akt-mTOR-GluA1 signaling, with the vHPC and the left IL vmPFC as the proposed neural correlates.
PubMed: 38931336
DOI: 10.3390/ph17060669 -
Nutrients Jun 2024Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there...
Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters.
Topics: Humans; Carpal Tunnel Syndrome; Vitamin D; Female; Vitamin D Deficiency; Male; Middle Aged; Electromyography; Adult; Treatment Outcome; Dietary Supplements; Adrenal Cortex Hormones; Median Nerve; Aged
PubMed: 38931299
DOI: 10.3390/nu16121947