Maintenance Of Function Research Articles

New concepts in the roles of AMPK in adipocyte stem cell biology.

Obesity is a major risk factor for many life-threatening diseases. Adipose tissue dysfunction is emerging as a driving factor in the transition from excess adiposity to comorbidities such as metabolic-associated fatty liver disease, cardiovascular disease, Type 2 diabetes and cancer. However, the transition from healthy adipose expansion to the development of these conditions is poorly understood. Adipose stem cells, residing in the vasculature and stromal regions of subcutaneous and visceral depots, are responsible for the expansion and maintenance of organ function, and are now recognised as key mediators of pathological transformation. Impaired tissue expansion drives inflammation, dysregulation of endocrine function and the deposition of lipids in the liver, muscle and around vital organs, where it is toxic. Contrary to previous hypotheses, it is the promotion of healthy adipose tissue expansion and function, not inhibition of adipogenesis, that presents the most attractive therapeutic strategy in the treatment of metabolic disease. AMP-activated protein kinase, a master regulator of energy homeostasis, has been regarded as one such target, due to its central role in adipose tissue lipid metabolism, and its apparent inhibition of adipogenesis. However, recent studies utilising AMP-activated protein kinase (AMPK)-specific compounds highlight a more subtle, time-dependent role for AMPK in the process of adipogenesis, and in a previously unexplored repression of leptin, independent of adipocyte maturity. In this article, I discuss historic evidence for AMPK-mediated adipogenesis inhibition and the multi-faceted roles for AMPK in adipose tissue.

BaP/BPDE suppresses homologous recombination repair in human trophoblast cells to induce miscarriage: The roles of lnc-HZ08

Benzo(a)pyrene (BaP) or benzo (a) pyrene 7,8-dihydrodiol-9,10-epoxide (BPDE) exposure causes trophoblast cell dysfunctions and induces miscarriage, which is generally epigenetically regulated. Homologous recombination (HR) repair of DNA double strand break (DSB) plays a crucial role in maintenance of genetic stability and cell normal functions. However, whether BaP/BPDE might suppress HR repair in human trophoblast cells to induce miscarriage, as well as its epigenetic regulatory mechanism, is largely unclear. In this study, we find that BaP/BPDE suppresses HR repair of DSB in trophoblast cells and eventually induces miscarriage by up-regulating lnc-HZ08. In mechanism, lnc-HZ08 (1) down-regulates the expression levels of FOXA1 (forkhead box A1) and thus suppresses FOXA1-mediated mRNA transcription of BRCA1 (Breast cancer susceptibility gene 1) and CtIP (CtBP-interacting protein), (2) impairs BRCA1 and CtIP protein interactions by competitive binding with CtIP through lnc-HZ08-1 fragment, and also (3) suppresses BRCA1-mediated CtIP ubiquitination without affecting CtIP stability, three of which eventually suppress HR repair in human trophoblast cells. Supplement with murine Ctip could efficiently restore (i.e. increase) HR repair and alleviate miscarriage in BaP-exposed mouse model. Collectively, this study not only reveals the association and causality among BaP/BPDE exposure, the defective HR repair, and miscarriage, but also discovers novel mechanism in lnc-HZ08-regulated BRCA1/CtIP-mediated HR repair, bridging epigenetic regulation and genetic instability and also providing an efficient approach for treatment against BaP/BPDE-induced unexplained miscarriage.

Intrinsic and Extrinsic Factors Associated with Hair Graying (Canities) and Therapeutic Potential of Plant Extracts and Phytochemicals

This review aims to gain insight into the major causes of hair graying (canities) and how plant-derived extracts and phytochemicals could alleviate this symptom. Research articles on human hair graying were searched and selected using the PubMed, Web of Science, and Google Scholar databases. We first examined the intrinsic and extrinsic factors associated with hair graying, such as the reduced capacity of melanin synthesis and transfer, exhaustion of melanocyte stem cells (MSCs) and melanocytes, genetics and epigenetics, race, gender, family history, aging, oxidative stress, stress hormones, systematic disorders, nutrition, smoking, alcohol consumption, lifestyle, medications, and environmental factors. We also examined various plants and phytochemicals that have shown a potential to interfere with the onset or progression of human hair graying at different levels from in vitro studies to clinical studies: the extract of Polygonum multiflorum and its major components, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside and emodin; the extract of Eriodictyon angustifolium and its major flavonoid compounds, hydroxygenkwanin, sterubin, and luteolin; the extracts of Adzuki beans (Vigna angularis), Fuzhuan brick tea (Camellia sinensis), and Gynostemma pentaphyllum; bixin, a carotenoid compound found in Bixa orellana; and rhynchophylline, an alkaloid compound found in certain Uncaria species. Experimental evidence supports the notion that certain plant extracts and phytochemicals could alleviate hair graying by enhancing MSC maintenance or melanocyte function, reducing oxidative stress due to physiological and environmental influences, and managing the secretion and action of stress hormones to an appropriate level. It is suggested that hair graying may be reversible through the following tactical approaches: selective targeting of the p38 mitogen-activated protein kinase (MAPK)–microphthalmia-associated transcription factor (MITF) axis, nuclear factor erythroid 2-related factor 2 (NRF2), or the norepinephrine–β2 adrenergic receptor (β2AR)–protein kinase A (PKA) signaling pathway.

Lysosomes drive the piecemeal removal of mitochondrial inner membrane.

Mitochondrial membranes define distinct structural and functional compartments. Cristae of the inner mitochondrial membrane (IMM) function as independent bioenergetic units that undergo rapid and transient remodelling, but the significance of this compartmentalized organization is unknown1. Using super-resolution microscopy, here we show that cytosolic IMM vesicles, devoid of outer mitochondrial membrane or mitochondrial matrix, are formed during resting state. These vesicles derived from the IMM (VDIMs) are formed by IMM herniation through pores formed by voltage-dependent anion channel 1 in the outer mitochondrial membrane. Live-cell imaging showed that lysosomes in proximity to mitochondria engulfed the herniating IMM and, aided by the endosomal sorting complex required for transport machinery, led to the formation of VDIMs in a microautophagy-like process, sparing the remainder of the organelle. VDIM formation was enhanced in mitochondria undergoing oxidative stress, suggesting their potential role in maintenance of mitochondrial function. Furthermore, the formation of VDIMs required calcium release by the reactive oxygen species-activated, lysosomal calcium channel, transient receptor potential mucolipin 1, showing an interorganelle communication pathway for maintenance of mitochondrial homeostasis. Thus, IMM compartmentalization could allow for the selective removal of damaged IMM sections via VDIMs, which should protect mitochondria from localized injury. Our findings show a new pathway of intramitochondrial quality control.

Non-Linear Association of Dietary Polyamines with the Risk of Incident Dementia: Results from Population-Based Cohort of the UK Biobank.

Natural polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are evolutionarily conserved endogenous molecules crucially involved in central cellular processes. Their physiological importance may extend to the maintenance of cognitive function during aging. However, limited population-based epidemiological studies have explored the link between dietary polyamines and dementia risk. This study was a prospective analysis of 77,092 UK Biobank participants aged ≥ 60 years without dementia at baseline. We used Cox proportional hazard regression models to explore the associations between dietary polyamines and the risk of dementia, and restricted cubic splines to test the non-linear relationships. During a median follow-up of 12 years, 1087 incidents of all-cause dementia cases occurred, including 450 Alzheimer's disease (AD) cases and 206 vascular dementia (VD) cases. The fully adjusted hazard ratios (HRs) for the upper fourth quintile of dietary SPD, in comparison with the lowest quintile of intake, were 0.68 (95% confidence interval [95% CI]: 0.66-0.83) for the risk of all-cause dementia, 0.62 (95% CI: 0.45-0.85) for AD and 0.56 (95% CI: 0.36-0.88) for VD, respectively. A 26% reduction in dementia risk [HR: 0.74, (95% CI: 0.61-0.89)] and a 47% reduction in AD [HR: 0.53, (95%CI: 0.39-0.72)] were observed comparing the third with the lowest quintiles of dietary SPM. Dietary PUT was only associated with a reduced risk of all-cause dementia in the fourth quintile [HR (95% CI): 0.82 (0.68-0.99)]. Reduced risk was not found to be significant across all quintiles. There were 'U'-shaped relationships found between dietary polyamines and all-cause dementia, AD and VD. Stratification by genetic predisposition showed no significant effect modification. Optimal intake of polyamines was linked to a decreased risk of dementia, with no modification by genetic risk. This potentially suggests cognitive benefits of dietary natural polyamines in humans.

Brain-consistent architecture for imagination.

Imagination represents a pivotal capability of human intelligence. To develop human-like artificial intelligence, uncovering the computational architecture pertinent to imaginative capabilities through reverse engineering the brain's computational functions is essential. The existing Structure-Constrained Interface Decomposition (SCID) method, leverages the anatomical structure of the brain to extract computational architecture. However, its efficacy is limited to narrow brain regions, making it unsuitable for realizing the function of imagination, which involves diverse brain areas such as the neocortex, basal ganglia, thalamus, and hippocampus. In this study, we proposed the Function-Oriented SCID method, an advancement over the existing SCID method, comprising four steps designed for reverse engineering broader brain areas. This method was applied to the brain's imaginative capabilities to design a hypothetical computational architecture. The implementation began with defining the human imaginative ability that we aspire to simulate. Subsequently, six critical requirements necessary for actualizing the defined imagination were identified. Constraints were established considering the unique representational capacity and the singularity of the neocortex's modes, a distributed memory structure responsible for executing imaginative functions. In line with these constraints, we developed five distinct functions to fulfill the requirements. We allocated specific components for each function, followed by an architectural proposal aligning each component with a corresponding brain organ. In the proposed architecture, the distributed memory component, associated with the neocortex, realizes the representation and execution function; the imaginary zone maker component, associated with the claustrum, accomplishes the dynamic-zone partitioning function; the routing conductor component, linked with the complex of thalamus and basal ganglia, performs the manipulation function; the mode memory component, related to the specific agranular neocortical area executes the mode maintenance function; and the recorder component, affiliated with the hippocampal formation, handles the history management function. Thus, we have provided a fundamental cognitive architecture of the brain that comprehensively covers the brain's imaginative capacities.

Bioprinting with superelastic and fatigue-resistant bioinks for large-sized tissue delivery

3D bioprinting technology is advancing rapidly to construct multi-scale preformed architectures that satisfy the demands of tissue regeneration. However, challenges remain in accurately delivering large-sized preformed architectures to the defect sites without being damaged by the mechanical environment in vivo. In this study, we proposed a versatile bioprinting strategy to fabricate large-sized architectures with remarkable injection capacity for geometry-independent minimally invasive tissue delivery. We design a novel hydrogel by mixing gelatin methacryloyl with poly(ethylene glycol) diacrylate (PEGDA) and photocrosslinking the mixture under a white light source. The hydrogel forms a reinforced crosslinking network, exhibiting superelasticity and fatigue resistance. We infer that the flexible chains of high-molecular-weight PEGDA and interconnected macropores of hydrogel contribute to the reinforcement mechanisms. With a decoupled bioprinting strategy, the bioink can be 3D printed into large-sized architectures with different geometries and tunable Poisson’s ratio. The printing architectures displayed excellent deformation and shape recovery capacity by compressing to less than 1% of the original size and fully recovering after injection. The injection capacity is geometry-independent, indicating the intrinsic properties of the hydrogel and allowing higher freedom for the structural design and geometry size of the architectures. The bioprinting process is compatible with genome-edited hepatic cells with high cell-bioprinting suitability, demonstrating high cell viability, a minimally altered transcriptomic profile after bioprinting, and a biocompatible microenvironment that supports cell survival and hepatic function maintenance. The cell-laden architectures express uncompromised injection capacity with unaffected cell viability after injection. This study presents a generalizable strategy for preparing and bioprinting with superelastic and fatigue-resistant bioinks into customized cell-laden architectures to facilitate minimally invasive large-sized tissue delivery.

Egg Consumption and 4-Year Change in Cognitive Function in Older Men and Women: The Rancho Bernardo Study.

The effect of dietary cholesterol on cognitive function is debatable. While eggs contain high levels of dietary cholesterol, they provide nutrients beneficial for cognitive function. This study examined the effects of egg consumption on change in cognitive function among 890 ambulatory adults (N = 357 men; N = 533 women) aged ≥55 years from the Rancho Bernardo Study who attended clinic visits in 1988-1991 and 1992-1996. Egg intake was obtained in 1988-1991 with a food frequency questionnaire. The Mini-Mental Status Exam (MMSE), Trails B, and category fluency were administered at both visits to assess cognitive performance. Sex-specific multiple regression analyses tested associations of egg intake with changes in cognitive function after adjustment for confounders. The mean time between visits was 4.1 ± 0.5 years; average ages were 70.1 ± 8.4 in men and 71.5 ± 8.8 in women (p = 0.0163). More men consumed eggs at higher levels than women; while 14% of men and 16.5% of women reported never eating eggs, 7.0% of men and 3.8% of women reported intakes ≥5/week (p = 0.0013). In women, after adjustment for covariates, egg consumption was associated with less decline in category fluency (beta = -0.10, p = 0.0241). Other associations were nonsignificant in women, and no associations were found in men. Results suggest that egg consumption has a small beneficial effect on semantic memory in women. The lack of decline observed in both sexes suggests that egg consumption does not have detrimental effects and may even have a role in the maintenance of cognitive function.

Alzheimer's disease risk gene CD2AP is a dose-sensitive determinant of synaptic structure and plasticity.

CD2-Associated protein (CD2AP) is a candidate susceptibility gene for Alzheimer's disease, but its role in the mammalian central nervous system remains largely unknown. We show that CD2AP protein is broadly expressed in the adult mouse brain, including within cortical and hippocampal neurons, where it is detected at pre-synaptic terminals. Deletion of Cd2ap altered dendritic branching and spine density, and impaired ubiquitin-proteasome system activity. Moreover, in mice harboring either one or two copies of a germline Cd2ap null allele, we noted increased paired-pulse facilitation at hippocampal Schaffer-collateral synapses, consistent with a haploinsufficient requirement for pre-synaptic release. Whereas conditional Cd2ap knockout in the brain revealed no gross behavioral deficits in either 3.5- or 12-month-old mice, Cd2ap heterozygous mice demonstrated subtle impairments in discrimination learning using a touchscreen task. Based on unbiased proteomics, partial or complete loss of Cd2ap triggered perturbation of proteins with roles in protein folding, lipid metabolism, proteostasis, and synaptic function. Overall, our results reveal conserved, dose-sensitive requirements for CD2AP in the maintenance of neuronal structure and function, including synaptic homeostasis and plasticity, and inform our understanding of possible cell-type specific mechanisms in Alzheimer's Disease.

Exploration of Synergistic Regulation Mechanisms of Cerebral Ganglion and Muscle in Eriocheir sinensis Activated in Response to Alkalinity Stress.

The cerebral ganglion and muscle are important regulatory tissues in Eriocheir sinensis. Therefore, it is of great significance to explore their synergistic roles in this organism's anti-stress response. In this study, proteomics, metabolomics, and combination analyses of the cerebral ganglion and muscle of E. sinensis under alkalinity stress were performed. The cerebral ganglion and muscle played a significant synergistic regulatory role in alkalinity adaptation. The key regulatory pathways involved were amino acid metabolism, energy metabolism, signal transduction, and the organismal system. They also played a modulatory role in the TCA cycle, nerve signal transduction, immune response, homeostasis maintenance, and ion channel function. In conclusion, the present study provides a theoretical reference for further research on the mechanisms regulating the growth and development of E. sinensis in saline-alkaline environments. In addition, it provides theoretical guidelines for promoting the vigorous development of the E. sinensis breeding industry in saline-alkaline environments in the future.

The Fanconi anemia core complex promotes CtIP-dependent end resection to drive homologous recombination at DNA double-strand breaks

During the repair of interstrand crosslinks (ICLs) a DNA double-strand break (DSB) is generated. The Fanconi anemia (FA) core complex, which is recruited to ICLs, promotes high-fidelity repair of this DSB by homologous recombination (HR). However, whether the FA core complex also promotes HR at ICL-independent DSBs, for example induced by ionizing irradiation or nucleases, remains controversial. Here, we identified the FA core complex members FANCL and Ube2T as HR-promoting factors in a CRISPR/Cas9-based screen. Using isogenic cell line models, we further demonstrated an HR-promoting function of FANCL and Ube2T, and of their ubiquitination substrate FANCD2. We show that FANCL and Ube2T localize at DSBs in a FANCM-dependent manner, and are required for the DSB accumulation of FANCD2. Mechanistically, we demonstrate that FANCL ubiquitin ligase activity is required for the accumulation of CtIP at DSBs, thereby promoting end resection and Rad51 loading. Together, these data demonstrate a dual genome maintenance function of the FA core complex and FANCD2 in promoting repair of both ICLs and DSBs.

Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism

Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain's most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial cell interactions in the healthy brain. To investigate the role of microglia at a healthy BBB, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed the BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for the maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism. This effect was independent from microglial depletion, suggesting that PLX5622 has off-target effects on brain vasculature.

Dexmedetomidine administration in a laryngeal cancer patient with emergency tracheostomy: a case report

The maintenance of vital functions in any patient depends upon the preservation and maintenance of airway patency. Conditions that may cause difficult airway, such as a laryngeal mass, require rapid and expert intervention. We briefly review the current knowledge on this subject by presenting the report of a patient who required emergency airway intervention and in whom a tracheostomy had to be resorted to under sedation. A 59-year-old male patient who was scheduled for total laryngectomy and neck dissection due to laryngeal cancer was taken to the operating room with the decision of emergency tracheostomy after developing respiratory distress. Nasoendoscopic visualization of the patient showed an exophytic lesion starting from the root of the tongue on the left and extending to the chordae. Inj fentanyl and dexmedetomidine were administered to the patient for sedation and dexmedetomidine infusion was continued after the loading dose. When the thyroid isthmus was encountered during the surgical intervention, a tracheostomy was made at 45 min. A 7.5 mm cuffed tube was inserted and respiratory control was achieved. This case report stresses that a combination of dexmedetomidine and fentanyl can be used safely in such cases. Keywords: tracheostomy, dexmedetomidine, diffuculut airway Citation: Kaya F, Evirgen ES, Aydin EU, Kocagil S, Erkiliç E. Dexmedetomidine administration in a laryngeal cancer patient with emergency tracheostomy: a case report. Anaesth. pain intensive care 2024;28(4):772−775; DOI: 10.35975/apic.v28i4.2522 Received: April 17, 2024; Reviewed: June 05, 2024; Accepted: June 05, 2024

Decreased Tongue-Lip Motor Function in Japanese Population with Low Taste Sensitivity: A Cross-Sectional Study.

Background/Objectives: Taste disorders have a negative impact on meal enjoyment, which is essential for maintaining adequate nutrition and quality of life. Japan is a rapidly aging society with an increasing number of individuals with taste disorders. However, despite the increasing prevalence of taste disorders, the correlation between oral frailty and taste sensitivity remains largely unknown. The objective of this study was to assess the relationship between oral health status and taste sensitivity among the Japanese population. Methods: Participants were recruited from Kanagawa Dental University Hospital Medical-Dental Collaboration Center between 2018 and 2021. The exclusion criteria were severe systemic infections, pregnancy, or lactation. Clinical examinations, oral function assessments, and taste tests were conducted using tap water and 1% sweet, 0.3% salty, 0.03% umami, and 0.1% umami tastants. The relationships between oral function, systemic indicators, and taste sensitivity were statistically evaluated. Results: Of the 169 participants included in this cross-sectional study, 39.6% were male and 60.4% were female (median age, 68 years). Participants with low taste sensitivity showed a decline in tongue-lip motor function, independent of age, sex, or smoking status. A multiple logistic regression analysis conducted using two age categories-younger than 65 years and older than 65 years-revealed an association between tongue-lip motor function and taste sensitivity among participants younger than 65 years. Conclusions: Decreased taste sensitivity is associated with tongue-lip motor function. Therefore, the early maintenance of oral function and taste sensitivity may be beneficial for optimal tongue-lip motor function.

Structural Perspectives on Metal Dependent Roles of Ferric Uptake Regulator (Fur).

Iron is crucial for the metabolism and growth of most prokaryotic cells. The ferric uptake regulator (Fur) protein plays a central role in regulating iron homeostasis and metabolic processes in bacteria. It ensures the proper utilization of iron and the maintenance of cellular functions in response to environmental cues. Fur proteins are composed of an N-terminal DNA-binding domain (DBD) and a C-terminal dimerization domain (DD), typically existing as dimers in solution. Fur proteins have conserved metal-binding sites named S1, S2, and S3. Among them, site S2 serves as a regulatory site, and metal binding at S2 results in conformational changes. Additionally, as a transcriptional regulator, Fur specifically binds to a consensus DNA sequence called the Fur box. To elucidate the structural and functional properties of Fur proteins, various structures of metal- or DNA-bound Fur proteins or apo-Fur proteins have been determined. In this review, we focus on the structural properties of Fur proteins according to their ligand-bound state and the drug development strategies targeting Fur proteins. This information provides valuable insights for drug discovery.

Low Calcium-High Magnesium Krebs-Henseleit Solution Combined with Adenosine and Lidocaine Improved Rat Aortic Function and Structure Following Cold Preservation.

Background and objectives: The main problem of vascular preservation is the maintenance of vessel graft quality and function following extended storage. Conventional preservation solutions such as histidine-tryptophan-ketoglutarate (HTK) solution, Phosphate-Buffer Solution (PBS), or sodium chloride 0.9% has been shown to be inadequate in preserving vascular physiological function after 3 days of cold storage. This study aimed to evaluate whether adenosine and lidocaine (AL) in a modified Krebs-Henseleit (KH) solution can preserve the function and histological structure of rat aortic rings after 6 days. Materials and Methods: Thirty-five aortic rings from male Wistar rats (200-300 g) were harvested and immediately immersed in one of the assigned cold preservation solutions: standard KH, modified KH (mod KH) with lower calcium (Ca2+) and higher magnesium content (Mg2+) with or without adenosine and lidocaine (mod KH-AL), and modified KH with AL, insulin, and melatonin (Mod KH-ALMI). The contraction and relaxation function of the aortic rings were examined using an isometric force transducer after 6 days of cold preservation. Hematoxylin and eosin staining were used to analyze the rings' histological structure. Results: Vascular contraction and relaxation functions were severely affected after a 6-day cold storage period in standard KH. Modifying the KH solution by reducing the Ca2+ and increasing the Mg2+ levels greatly recovered the vessel functions. The addition of AL or ALMI to the modified KH did not further recover vascular contractility. However, only the addition of AL to the modified KH increased the ACh-induced relaxation at 6 days when compared to the conventional KH, suggesting that endothelium preservation is improved. From histological analysis, it was found that the addition of AL but not ALMI further improved the endothelial lining and the structure of the elastic membrane layers of the preserved vessels after 6 days of cold preservation. Conclusions: The addition of AL to low calcium-high magnesium KH solution significantly enhanced endothelial preservation and improved endothelial-induced relaxation of preserved vessels after 6 days of cold storage.

Shallow Groundwater Around Plateau Lakes： Spatiotemporal Distributions of Dissolved Carbon and Its Driving Factors

Dissolved carbon in groundwater plays an important role in carbon cycling and ecological function maintenance, and its concentration level affects the migration and transformation of pollutants in groundwater. To understand the spatiotemporal variation characteristics of dissolved carbon and its driving factors in shallow groundwater around plateau lakes, variations in the concentrations of dissolved organic carbon （DOC）, inorganic carbon （DIC）, and total carbon （DTC） and their driving factors in shallow groundwater （n = 404） around eight plateau lakes were analyzed. The results indicated that the average values of ρ（DOC）, ρ（DIC）, and ρ（DTC） in shallow groundwater around plateau lakes were 8.23, 49.01, and 57.84 mg·L-1, respectively, with the ρ（DOC） in 79.0% of shallow groundwater samples exceeding 5 mg·L-1. There were no significant differences in the DOC, DIC, and DTC concentrations between rainy and dry seasons, whereas the change in dissolved carbon concentrations in shallow groundwater were strongly affected by the intensity of agricultural intensification and the depth of groundwater table； the DOC, DIC, and DTC concentrations in shallow groundwater from facility agricultural regions （SFAR）, cropland fallow agricultural regions （CFAR）, and intensive agricultural regions with deeper groundwater tables （DIAR） were significantly reduced by 25.8% - 56.6%, 14.0% - 32.9%, and 16.6% - 36.7%, respectively, compared with those in intensive agricultural regions with shallower groundwater tables （SIAR）. Additionally, the dissolved carbon concentrations in shallow groundwater from DIAR were significantly lower than those of SFAR and CFAR. RDA revealed that physicochemical factors in water and soil significantly explained the changes in the dissolved carbon concentrations. Moreover, the dissolved carbon concentrations in shallow groundwater around Yilong Lake were significantly higher than those of other lakes, whereas that of Chenghai Lake was significantly lower than that of other lakes. Our study highlights that agricultural intensification intensity and groundwater table depth jointly drove the variations in dissolved carbon concentrations in shallow groundwater around plateau lakes. The study results are expected to provide a scientific basis for understanding the carbon cycle in plateau lake areas with underground runoff flowing into lakes and evaluating the attenuation of pollutants by dissolved carbon in shallow groundwater.

Temperature and biodiversity influence community stability differently in birds and fishes.

Determining the factors that affect community stability is crucial to understanding the maintenance of biodiversity and ecosystem functioning in the face of global warming. We investigated how four temperature components (that is, median, variability, trend and extremes) affected diversity-synchrony-stability relationships for 1,246 bird and 580 fish communities from temperate regions. We hypothesized a stabilizing effect on the community if the variation in species' response to changing median temperature decreases overall community synchrony (hypothesis H1) and if temperature extremes reduce interspecific synchrony at extreme abundances due to variation in species' thermal tolerance limits (hypothesis H2). We found support for H1 in fish and for H2 in bird communities. Here we showed that the abiotic components (that is, the median, variability, trend and extremes of temperature) had more indirect effects on community stability, predominantly by affecting the biotic components (that is, diversity, synchrony). Considering various temperature components' direct as well as indirect impacts on stability for terrestrial versus aquatic communities will improve our mechanistic understanding of biodiversity change in response to global climatic stressors.

Approach to gait disorders and orthotic management in adult onset neuromuscular diseases.

In order to understand abnormal gait, this article will first review normal gait, discuss how neuromuscular diseases disturb gait patterns and review orthotic interventions. In normal gait, concentric contractions accelerate and eccentric contractions decelerate the limb. Neuromuscular gait disorders can be grouped into (1) proximal weakness, (2) distal weakness, (3) nonlength-dependent or generalized weakness, (4) asymmetric weakness, and (5) sensory disorders. Identification of gait disturbance type in neuromuscular diseases leads to the appropriate orthotic prescription since orthotic strategies are grouped into (1) proximal weakness, (2) distal weakness, and (3) sensory disturbances. Orthotics is not indicated in all types of gait disturbance. Weakness in proximal hip musculature can be managed with gait aids such as walkers. In contrast, distal muscle weakness can be managed with orthotics. Preservation of gait assists in maintenance of daily function and integration in society.

BDNF-Regulated Modulation of Striatal Circuits and Implications for Parkinson's Disease and Dystonia.

Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival, and plasticity. BDNF is necessary for neuronal and functional maintenance in the striatum and the substantia nigra, both structures involved in the pathogenesis of Parkinson's Disease (PD). Depletion of BDNF leads to striatal degeneration and defects in the dendritic arborization of striatal neurons. Activation of tropomyosin receptor kinase B (TrkB) by BDNF is necessary for the induction of long-term potentiation (LTP), a form of synaptic plasticity, in the hippocampus and striatum. PD is characterized by the degeneration of nigrostriatal neurons and altered striatal plasticity has been implicated in the pathophysiology of PD motor symptoms, leading to imbalances in the basal ganglia motor pathways. Given its essential role in promoting neuronal survival and meditating synaptic plasticity in the motor system, BDNF might have an important impact on the pathophysiology of neurodegenerative diseases, such as PD. In this review, we focus on the role of BDNF in corticostriatal plasticity in movement disorders, including PD and dystonia. We discuss the mechanisms of how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Evidence for alterations of BDNF and TrkB in PD patients and animal models are reviewed, and the potential of BDNF to act as a therapeutic agent is highlighted. Advancing our understanding of these mechanisms could pave the way toward innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases.