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Frontiers in Human Neuroscience 2024Human brain imaging research using functional MRI (fMRI) has uncovered flexible variations in the functional connectivity between brain regions. While some of this... (Review)
Review
Human brain imaging research using functional MRI (fMRI) has uncovered flexible variations in the functional connectivity between brain regions. While some of this variability likely arises from the pattern of information flow through circuits, it may also be influenced by rapid changes in effective synaptic strength at the molecular level, a phenomenon called Dynamic Network Connectivity (DNC) discovered in non-human primate circuits. These neuromodulatory molecular mechanisms are found in layer III of the macaque dorsolateral prefrontal cortex (dlPFC), the site of the microcircuits shown by Goldman-Rakic to be critical for working memory. This research has shown that the neuromodulators acetylcholine, norepinephrine, and dopamine can rapidly change the strength of synaptic connections in layer III dlPFC by (1) modifying the depolarization state of the post-synaptic density needed for NMDA receptor neurotransmission and (2) altering the open state of nearby potassium channels to rapidly weaken or strengthen synaptic efficacy and the strength of persistent neuronal firing. Many of these actions involve increased cAMP-calcium signaling in dendritic spines, where varying levels can coordinate the arousal state with the cognitive state. The current review examines the hypothesis that some of the dynamic changes in correlative strength between cortical regions observed in human fMRI studies may arise from these molecular underpinnings, as has been seen when pharmacological agents or genetic alterations alter the functional connectivity of the dlPFC consistent with the macaque physiology. These DNC mechanisms provide essential flexibility but may also confer vulnerability to malfunction when dysregulated in cognitive disorders.
PubMed: 38384333
DOI: 10.3389/fnhum.2024.1353043 -
Frontiers in Oncology 2016An increase of cellular phosphocholine (PC) and total choline (tCho)-containing compounds as well as alterations in lipids have been consistently observed in cancer...
An increase of cellular phosphocholine (PC) and total choline (tCho)-containing compounds as well as alterations in lipids have been consistently observed in cancer cells and tissue. These metabolic changes are closely related to malignant transformation, invasion, and metastasis. The study of cancer cells in culture plays an important role in understanding mechanisms leading to altered choline (Cho) and lipid metabolism in cancer, as it provides a carefully controlled environment. However, a solid tumor is a complex system with a unique tumor microenvironment frequently containing hypoxic and acidic regions and areas of nutrient deprivation and necrosis. Cancer cell-stromal cell interactions and the extracellular matrix may also alter Cho and lipid metabolism. Human tumor xenograft models in mice are useful to mimic the growth of human cancers and provide insights into the influence of conditions on metabolism. Here, we have compared metabolites, obtained with high resolution H MRS of extracts from human breast and prostate cancer cells in a 2-dimensional (2D) monolayer culture and from solid tumor xenografts derived from these cells, as well as the protein expression of enzymes that regulate Cho and lipid metabolism. Our data demonstrate significant differences in Cho and lipid metabolism and protein expression patterns between human breast and prostate cancer cells in culture and in tumors derived from these cells. These data highlight the influence of the tumor microenvironment on Cho and lipid metabolism.
PubMed: 28066718
DOI: 10.3389/fonc.2016.00262 -
Neurobiology of Stress Dec 2016The ubiquitous and intense nature of stress responses necessitate that we understand how they affect decision-making. Despite a number of studies examining risky...
The ubiquitous and intense nature of stress responses necessitate that we understand how they affect decision-making. Despite a number of studies examining risky decision-making under stress, it is as yet unclear whether and in what way stress alters the underlying processes that shape our choices. This is in part because previous studies have not separated and quantified dissociable valuation and decision-making processes that can affect choices of risky options, including risk attitudes, loss aversion, and choice consistency, among others. Here, in a large, fully-crossed two-day within-subjects design, we examined how acute stress alters risky decision-making. On each day, 120 participants completed either the cold pressor test or a control manipulation with equal probability, followed by a risky decision-making task. Stress responses were assessed with salivary cortisol. We fit an econometric model to choices that dissociated risk attitudes, loss aversion, and choice consistency using hierarchical Bayesian techniques to both pool data and allow heterogeneity in decision-making. Acute stress was found to have no effect on risk attitudes, loss aversion, or choice consistency, though participants did become more loss averse and more consistent on the second day relative to the first. In the context of an inconsistent previous literature on risk and acute stress, our findings provide strong and specific evidence that acute stress does not affect risk attitudes, loss aversion, or consistency in risky monetary decision-making.
PubMed: 27981193
DOI: 10.1016/j.ynstr.2016.10.003 -
Autism Research : Official Journal of... Jun 2023Most individuals show a small bias towards visual stimuli presented in their left visual field (LVF) that reflects right-hemispheric specialization of visuospatial... (Review)
Review
Most individuals show a small bias towards visual stimuli presented in their left visual field (LVF) that reflects right-hemispheric specialization of visuospatial functions. Moreover, this bias is altered by some neurodevelopmental disorders, suggesting they may be linked to changes in hemispheric asymmetry. To examine whether autism potentially alters hemispheric asymmetry, we conducted a systematic search of scientific databases to review existing literature on the link between autism and alterations in visuospatial bias. This search identified 13 publications that had explored this issue using a wide range of experimental designs and stimuli. Evidence of reduced LVF bias associated with autism was most consistent for studies examining attentional bias or preference measured using tasks such as line bisection. Findings for studies examining attentional performance (e.g., reaction time) were more equivocal. Further investigation is called for, and we make several recommendations for how this avenue of research can be extended.
Topics: Humans; Visual Perception; Functional Laterality; Autistic Disorder; Autism Spectrum Disorder; Attention; Space Perception
PubMed: 37243312
DOI: 10.1002/aur.2956 -
Frontiers in Oncology 2022The aim of this study is to determine the clinical efficacy of bile-derived liquid biopsy compared with plasma and tumor tissue biopsy in patients with biliary tract...
OBJECTIVE
The aim of this study is to determine the clinical efficacy of bile-derived liquid biopsy compared with plasma and tumor tissue biopsy in patients with biliary tract carcinoma (BTC).
METHODS
A total of 13 patients with BTC were enrolled in this cohort. Tumor tissue, bile, and plasma samples were obtained and analyzed using next-generation sequencing for genomic profiling.
RESULTS
Bile and plasma samples were collected from all 13 patients, and 11 patients also had matched tumor tissues available. The cell-free DNA (cfDNA) concentration was significantly higher in the bile supernatant than in plasma (median: 1918 vs. 63.1 ng/ml, p = 0.0017). The bile supernatant and pellet had a significantly higher mean mutation allele frequency (MF) than plasma (median: 3.84% vs. 4.22% vs. 0.16%; p < 0.001). Genomic alterations were predominantly missense. Both bile supernatant and pellet had significantly more genomic alterations than plasma (average: 9.3 vs. 7.2 vs. 2.3 alterations per sample; p < 0.01). Among the top 10 most frequent genomic alterations, the consistency between bile supernatant and tumor tissue was 90.00% (18/20), that between bile pellet and tumor tissue was 85.00% (17/20), and that between the plasma and tissue was only 35.00% (7/20). MAF of both bile supernatant and pellet was positively correlated with that in tissue samples (ρ < 0.0001, spearman r = 0.777, and ρ < 0.0001, spearman r = 0.787, respectively), but no significant correlation with tissue was found in the plasma (ρ = 0.966, spearman r = 0.008). Furthermore, additional genomic alterations could be detected in bile supernatant and pellet than in tissue. Potential targets for targeted therapy were identified in bile supernatant and pellet. Regarding copy number variation (CNV) and chromosomal instability (CIN) detection, four additional CNVs from two patients were detected in the bile supernatant that was not detected in tissues (i.e., amplification of , , , and ). CIN was significantly higher in tumor tissue than in plasma. The CIN of the bile was also significantly higher than that of plasma. There was no significant difference in CIN between the tissue and the bile supernatant.
CONCLUSION
The consistency of all genomic alterations and tumor tissue-determined genomic alteration in the bile supernatant/pellet was significantly higher than in plasma. Bile supernatants/pellets are better for genetic sequencing and may also have potential clinical value to guide targeted therapy and evaluate prognosis. Bile cfDNA may be a feasible substitute for tumor tissue in the genetic testing of patients with BTC.
PubMed: 36091112
DOI: 10.3389/fonc.2022.961939 -
Physiology & Behavior Feb 2019Down syndrome (DS) in humans is associated with differences of the central nervous system and oromotor development. DS also increases risks for pediatric feeding...
Down syndrome (DS) in humans is associated with differences of the central nervous system and oromotor development. DS also increases risks for pediatric feeding challenges, which sometimes involve the use of altered food consistencies. Therefore, experimental food consistency paradigms are of interest to oromotor investigations in mouse models of Down syndrome (DS). The present work reports impacts of an altered food consistency paradigm on the Ts65Dn and Dp(16)1Yey mouse models of DS, and sibling control mice. At weaning, Ts65Dn, Dp(16)1Yey and respective controls were assigned to receive either a hard food or a soft food (eight experimental groups, n = 8-10 per group). Two weeks later, mice were assessed for mastication speeds and then euthanized for muscle analysis. Soft food conditions were associated with significantly smaller weight gain (p = .003), significantly less volitional water intake through licking (p = .0001), and significant reductions in size of anterior digastric myofibers positive for myosin heavy chain isoform (MyHC) 2b (p = .049). Genotype was associated with significant differences in weight gain (p = .004), significant differences in mastication rate (p = .001), significant differences in a measure of anterior digastric muscle size (p = .03), and significant reductions in size of anterior digastric myofibers positive for MyHC 2a (p = .04). In multiple measures, the Ts65Dn model of DS was more affected than other genotype groups. Findings indicate a soft food consistency condition in mice is associated with significant reductions in weight gain and oromotor activity, and may impact digastric muscle. This suggests extended periods of food consistency modifications may have impacts that extend beyond their immediate roles in facilitating deglutition.
Topics: Animals; Disease Models, Animal; Down Syndrome; Eating; Food; Mastication; Mice; Muscle Contraction; Muscle, Skeletal; Myosin Heavy Chains
PubMed: 30496741
DOI: 10.1016/j.physbeh.2018.11.031 -
Neurobiology of Learning and Memory Jan 2022The neurobiology of emotion and episodic memory are well-researched subjects, as is their intersection: memory of emotional events (i.e. emotional memory). We and others...
The neurobiology of emotion and episodic memory are well-researched subjects, as is their intersection: memory of emotional events (i.e. emotional memory). We and others have previously demonstrated that the emotional valence of stimuli is encoded in the dorsal hippocampus, a structure integral to the acquisition, consolidation and retrieval of long-term episodic memories. Such findings are consistent with the idea that the emotional valence of stimuli contributes to the "what" component of episodic memories ("where" and "when" being the other components). We hypothesized that being in a heightened emotional state by itself does not contribute to the "what" component of episodic memories. We tested an inference of this hypothesis - that negative emotional state does not alter re-encoding of a spatial episodic event. Rats from the experimental group explored a novel place at their baseline emotional state (Event 1) and 20 min later re-explored the same place (Event 2) in a negative emotional state induced by a state-altering event prior to Event 2. We examined neuronal ensembles that induced expression of Arc and Homer1a, two immediate-early genes (IEGs) necessary for synaptic plasticity and consolidation of long-term memories, during both events. We found that in dorsal CA1 and dorsal CA3, Event 1 and Event 2 induced IEG expression in different neuronal ensembles. This finding was reflected in a low Fidelity score, which assesses the percentage of the Event 1 IEG-expressing ensemble re-activated during Event 2. The Fidelity score was significantly higher in a control group which was at a baseline emotional state during Event 2. Groups which were matched for non-specific disruptions from the state-altering event had intermediate Fidelity scores in dorsal CA1. The Fidelity scores of the dorsal CA3 in the latter groups were similar to those of the control group. Combined, the findings reject the tested hypothesis and suggest that a negative emotional state is encoded in the hippocampus as part of the long-term memory of episodic events that lack explicit emotion-inducing stimuli. These findings also suggest that individuals who often experience strong negative emotional states incorporate these states into ongoing non-emotional episodic memories.
Topics: Animals; Emotions; Genes, Immediate-Early; Hippocampus; Male; Memory, Episodic; Memory, Long-Term; Neuronal Plasticity; Neurons; Rats
PubMed: 34848328
DOI: 10.1016/j.nlm.2021.107562 -
JAMA Facial Plastic Surgery Dec 2019The tripod theory of the upper nasal third parallels the concept of the well-known nasal tip tripod. We are evaluating the idea that one can simply alter the upper nasal...
IMPORTANCE
The tripod theory of the upper nasal third parallels the concept of the well-known nasal tip tripod. We are evaluating the idea that one can simply alter the upper nasal angles reliably without the complex physics associated with the nasal tip to achieve a pleasing cosmetic result.
OBJECTIVE
To describe a concept related to the well-known tripod theory with extrapolation to the upper nasal third as it pertains to cosmetic rhinoplasty.
DESIGN, SETTING, AND PARTICIPANTS
This is a prospective study in which lateral photographs of 3 women who had not undergone surgery (age range, 20-50 years) were selected for digital manipulation of the nasal radix with subsequent alteration of the nasofrontal and nasofacial angles via imaging software. The altered images were analyzed by 20 blinded individuals between July 2009 and June 2017 to assess how changes in the height of the nasal dorsum and radix alone affect nasal appearance and the perception of ideal nasal angles. The study took place at a tertiary center, and the patients chosen for evaluation had nasal architecture that only required subtle changes rather than structure that demonstrated glaringly obvious overprojection or underprojection and rotation or a large dorsal bony hump. Analysis began June 2018.
MAIN OUTCOMES AND MEASURES
Overall trend in recognition of objective and subjective alterations in projection and rotation for the rhinoplasty- and non-rhinoplasty-trained evaluators.
RESULTS
Ten medically trained and 10 lay individuals (13 women [65%]; mean [SD] age, 38 [8.6] years) analyzed digitally manipulated photographs of 3 women (age range, 20-50 years) who had not undergone surgery. Lay individuals were more likely to choose an ideal nasal profile based on surrounding facial architecture (28 of 30 [93%]), while individuals with rhinoplasty training tended to separate the ideal nose from the surrounding face (18 of 30 [60%]) (P < .001). Projection was consistently and accurately recognized as being altered by both rhinoplasty-trained and lay individuals (95% CI, -0.18 to 0.38; P = .60 and 95% CI, -0.26 to 0.33; P > .99 for most and least projected), whereas subjective changes in rotation were significantly more elusive to the lay individual (95% CI, -0.04 to 0.52; P = .12 and 95% CI, 0.11 to 0.65; P = .01 for most and least rotated).
CONCLUSIONS AND RELEVANCE
Predictable and consistent aesthetic results are the primary aim in rhinoplasty. Alterations in the upper nasal tripod are more reliable with extrapolated healing than with the tripod of the nasal tip. Ultimately, simple alteration of the upper nasal third can result in an improved nasal profile without specific alteration of tip architecture.
LEVEL OF EVIDENCE
NA.
Topics: Adult; Esthetics; Face; Female; Humans; Image Processing, Computer-Assisted; Middle Aged; Nose; Photography; Prospective Studies; Rhinoplasty; Social Perception
PubMed: 31647524
DOI: 10.1001/jamafacial.2019.0884 -
Journal of Animal Science Nov 2020Corn is a common energy source in pig diets globally; when financially warranted, industrial corn coproducts, such as corn distiller's dried grains with solubles (DDGS),... (Review)
Review
Corn is a common energy source in pig diets globally; when financially warranted, industrial corn coproducts, such as corn distiller's dried grains with solubles (DDGS), are also employed. The energy provided by corn stems largely from starch, with some contribution from protein, fat, and non-starch polysaccharides (NSP). When corn DDGS are used in the diet, it will reduce starch within the diet; increase dietary protein, fat, and NSP levels; and alter the source profile of dietary energy. Arabinoxylans (AXs) comprise the majority of NSP in corn and its coproducts. One strategy to mitigate the antinutritive effects of NSP and improve its contribution to energy is by including carbohydrases within the diet. Xylanase is a carbohydrase that targets the β-1,4-glycosidic bonds of AX, releasing a mixture of smaller polysaccharides, oligosaccharides, and pentoses that could potentially be used by the pig. Xylanase is consistently effective in poultry production and moderately consistent in wheat-based swine diets, but its efficacy in corn-based swine diets is quite variable. Xylanase has been shown to improve the digestibility of various components of swine-based diets, but this seldom translates into an improvement in growth performance. Indeed, a review of xylanase literature conducted herein suggests that xylanase improves the digestibility of dietary fiber at least 50% of the time in pigs fed corn-based diets, but only 33% and 26% of the time was there an increase in average daily gain or feed efficiency, respectively. Intriguingly, there has been an abundance of reports proposing xylanase alters intestinal barrier integrity, inflammatory responses, oxidative status, and other health markers in the pig. Notably, xylanase has shown to reduce mortality in both high and low health commercial herds. These inconsistencies in performance metrics, and unexpected health benefits, warrant a greater understanding of the in vivo mechanism(s) of action (MOA) of xylanase. While the MOA of xylanase has been postulated considerably in the literature and widely studied in in vitro settings, in wheat-based diets, and in poultry, there is a dearth of understanding of the in vivo MOA in pigs fed corn-based diets. The purpose of this review is to explore the role of xylanase in corn-based swine diets, discuss responses observed when supplemented in diets containing corn-based fiber, suggest potential MOA of xylanase, and identify critical research gaps.
Topics: Animal Feed; Animals; Diet; Dietary Fiber; Dietary Supplements; Energy Intake; Glycoside Hydrolases; Intestines; Male; Swine; Triticum; Xylans; Zea mays
PubMed: 32970148
DOI: 10.1093/jas/skaa318 -
BioRxiv : the Preprint Server For... Nov 2023Older adults have difficulty maintaining balance when faced with postural disturbances, a task that is influenced by the stiffness of the triceps surae and Achilles...
Older adults have difficulty maintaining balance when faced with postural disturbances, a task that is influenced by the stiffness of the triceps surae and Achilles tendon. Age-related changes in Achilles tendon stiffness have been reported at matched levels of effort, but measures typically have not been made at matched loads, which is important due to age-dependent changes in strength. Moreover, age-dependent changes in muscle stiffness have yet to be tested. Here, we investigate how age alters muscle and tendon stiffness and their influence on ankle stiffness. We hypothesized that age-related changes in muscle and tendon contribute to reduced ankle stiffness in older adults and evaluated this hypothesis when either load or effort were matched. We used B-mode ultrasound with joint-level perturbations to quantify ankle, muscle, and tendon stiffness across a range of loads and efforts in seventeen healthy younger and older adults. At matched loads, there was no significant difference in ankle, muscle, or tendon stiffness between groups (all p>0.13). However, at matched effort, older adults exhibited a significant decrease in ankle (27%; p=0.008), muscle (37%; p=0.02), and tendon stiffness (22%; p=0.03) at 30% of maximum effort. This is consistent with our finding that older adults were 36% weaker than younger adults in plantarflexion (p=0.004). Together these results indicate that, at the loads tested in this study, there are no age-dependent changes in the mechanical properties of muscle or tendon, only differences in strength that result in altered ankle, muscle, and tendon stiffness at matched levels of effort.
PubMed: 38045313
DOI: 10.1101/2023.11.25.568676