Neural mechanisms of respiratory interoception Chan, Pei-Ying Sarah; Lee, Lu-Yuan; Davenport, Paul W.
Autonomic neuroscience,
June 2024, 2024-Jun, 2024-06-00, 20240601, Letnik:
253
Journal Article
Recenzirano
Odprti dostop
Respiratory interoception is one of the internal bodily systems that is comprised of different types of somatic and visceral sensations elicited by different patterns of afferent input and ...respiratory motor drive mediating multiple respiratory modalities. Respiratory interoception is a complex system, having multiple afferents grouped into afferent clusters and projecting into both discriminative and affective centers that are directly related to the behavioral assessment of breathing. The multi-afferent system provides a spectrum of input that result in the ability to interpret the different types of respiratory interceptive sensations. This can result in a response, commonly reported as breathlessness or dyspnea. Dyspnea can be differentiated into specific modalities. These respiratory sensory modalities lead to a general sensation of an Urge-to-Breathe, driven by a need to compensate for the modulation of ventilation that has occurred due to factors that have affected breathing. The multiafferent system for respiratory interoception can also lead to interpretation of the sensory signals resulting in respiratory related sensory experiences, including the Urge-to-Cough and Urge-to-Swallow. These behaviors are modalities that can be driven through the differentiation and integration of multiple afferent input into the respiratory neural comparator. Respiratory sensations require neural somatic and visceral interoceptive elements that include gated attention and detection leading to respiratory modality discrimination with subsequent cognitive decision and behavioral compensation. Studies of brain areas mediating cortical and subcortical respiratory sensory pathways are summarized and used to develop a model of an integrated respiratory neural network mediating respiratory interoception.
Polyamines are organic polycations essential for cell growth and differentiation; their aberrant accumulation is often associated with diseases, including many types of cancer. To maintain polyamine ...homeostasis, the catalytic activity and protein abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by the regulatory proteins antizyme isoform 1 (Az₁) and antizyme inhibitor (AzIN). Az₁ suppresses polyamine production by inhibiting the assembly of the functional ODC homodimer and, most uniquely, by targeting ODC for ubiquitin-independent proteolytic destruction by the 26S proteasome. In contrast, AzIN positively regulates polyamine levels by competing with ODC for Az₁ binding. The structural basis of the Az₁-mediated regulation of polyamine homeostasis has remained elusive. Here we report crystal structures of human Az₁ complexed with either ODC or AzIN. Structural analysis revealed that Az₁ sterically blocks ODC homodimerization. Moreover, Az₁ binding triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC, which illustrates how a substrate protein may be primed upon association with Az₁ for ubiquitin-independent proteasome recognition. Dynamic and functional analyses further indicated that the Az₁-induced binding and degradation of ODC by proteasome can be decoupled, with the intrinsically disordered C-terminal tail fragment of ODC being required only for degradation but not binding. Finally, the AzIN–Az₁ structure suggests how AzIN may effectively compete with ODC for Az₁ to restore polyamine production. Taken together, our findings offer structural insights into the Az-mediated regulation of polyamine homeostasis and proteasomal degradation.
Teratoma-like formation addresses a critical safety concern for the potential utility of induced pluripotent stem cells (iPSCs). Therefore, therapy utilizing iPSC-derived conditioned medium (iPSC-CM) ...for acute kidney injury (AKI) has attracted substantial interest. A recent study showed that iPSC-CM effectively alleviated ventilator-induced lung injury in rats. It prompts us to assess the therapeutic effects of iPSC-CM on ischemic AKI. First, we assessed the changes in renal function and tubular cell apoptosis by intraperitoneal administration of iPSC-CM to ischemia–reperfusion (I/R) rats. Second, we explored the oxidative stress-related pathway in the apoptosis of renal tubular cells subjected to hypoxia–reoxygenation (H/R). Administration of iPSC-CM significantly improved renal function and protected tubular cells against apoptosis in rats with I/R-AKI, and the optimal effect was observed at the 50-fold concentrated iPSC-CM. iPSC-CM also mitigated the H/R-induced apoptosis of NRK-52E cells in vitro. Reactive oxygen species (ROS) production was augmented in kidneys following I/R and in NRK-52E cells subjected to H/R. Meanwhile, expressions of phosphorylated p38 MAPK, TNF-α, and cleaved caspase 3 and NF-κB activity were consistently increased in vivo and in vitro. Following administration of iPSC-CM, ROS production was abolished, and inflammatory cytokine expression was significantly suppressed. Annexin V–propidium iodide flow cytometry and in situ TUNEL assay further showed that iPSC-CM markedly attenuated H/R- or I/R-induced tubular cell apoptosis. Intriguingly, treatment with iPSC-CM significantly improved the survival of rats with I/R-induced AKI. iPSC-CM represents a favorable source of stem cell-based therapy and may serve as a potential therapeutic strategy for kidney repair in ischemic AKI.
There is limited research exploring the changing clinical practices among healthcare providers (HPs) care for patients with Emergency Department (ED)-initiated Medication for Opioid Use Disorder ...(MOUD).
This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus for related studies from inception through October 12, 2022. Following the application of inclusion and exclusion criteria, 16 studies were included. Subsequently, they were charted and analyzed thematically based on ecological systems theory.
The main determinants in the four ecological systems were generated as follows: (1) microsystem: willingness and attitude, professional competence, readiness, and preference; (2) mesosystem: ED clinical practices, departmental factors; (3) exosystem: multidisciplinary approaches, discharge planning, and (4) macrosystem: stigma, health insurance, policy. The findings have implications for HPs and researchers, as insufficient adoption, implementation, and retention of MOUD in the ED affect clinical practices.
Across the four ecological systems, ED-initiated MOUD is shaped by multifaceted determinants. The microsystem underscores pivotal patient-HP trust dynamics, while the mesosystem emphasizes interdepartmental synergies. Exosystemically, resource allocation and standardized training remain paramount. The macrosystem reveals profound effects of stigma, insurance disparities, and evolving policies on treatment access and efficacy. Addressing these interconnected barriers is crucial for optimizing patient outcomes in the context of MOUD.
Myotonic dystrophy type 1 (DM1) is caused by an expansion of CTG repeats in the 3' untranslated region (UTR) of the dystrophia myotonia protein kinase (DMPK) gene. Cognitive impairment associated ...with structural change in the brain is prevalent in DM1. How this histopathological abnormality during disease progression develops remains elusive. Nuclear accumulation of mutant DMPK mRNA containing expanded CUG RNA disrupting the cytoplasmic and nuclear activities of muscleblind-like (MBNL) protein has been implicated in DM1 neural pathogenesis. The association between MBNL dysfunction and morphological changes has not been investigated. We generated a mouse model for postnatal expression of expanded CUG RNA in the brain that recapitulates the features of the DM1 brain, including the formation of nuclear RNA and MBNL foci, learning disability, brain atrophy and misregulated alternative splicing. Characterization of the pathological abnormalities by a time-course study revealed that hippocampus-related learning and synaptic potentiation were impaired before structural changes in the brain, followed by brain atrophy associated with progressive reduction of axon and dendrite integrity. Moreover, cytoplasmic MBNL1 distribution on dendrites decreased before dendrite degeneration, whereas reduced MBNL2 expression and altered MBNL-regulated alternative splicing was evident after degeneration. These results suggest that the expression of expanded CUG RNA in the DM1 brain results in neurodegenerative processes, with reduced cytoplasmic MBNL1 as an early event response to expanded CUG RNA.
Epidemiological studies have linked herbicides and Parkinson's disease (PD), with the strongest associations resulting from long exposure durations. Paraquat (PQ), an herbicide, induces PD-like ...syndromes and has widely been accepted as a PD mimetic. Currently, there is still no cure to prevent the progression of PD, and the search for effective therapeutic ways is urgent. Recently, the impairing activity of sirtuins (SIRTs), such as SIRT1, may correlate with PD etiology. However, the nonspecificity of SIRT1 agonists has made the protective mechanisms against PD unclear and hampered the therapeutic application of SIRT1. Thus, this study investigated the protective mechanism and therapeutic potential of SRT1720, a more specific agonist for SIRT1 synthesized by Sirtris, in alleviating the toxicity of PQ-induced cellular and animal models of PD. Here we show that SRT1720 alleviates PQ-induced toxicity in cell and animal models. Genetic silencing and pharmacological inhibition of SIRT1 attenuated SRT1720's protection against PQ-induced toxicity. Moreover, SRT1720 not only attenuated PQ-induced increased oxidative stress and mitochondrial free radical formations but also decreased mitochondrial membrane potential. Furthermore, SRT1720 reversed PQ-induced decreased PGC-1α levels and mitochondrial biogenesis. Although PQ and SRT1720 elevated NRF2 and antioxidative enzyme levels, only PQ decreased antioxidative enzyme activity but not SRT1720. NRF2 and PGC-1α silencing attenuated SRT1720 protection against PQ-induced toxicity. SRT1720 targeted SIRT1 and activated downstream PGC-1α and NRF2 signalings to prevent PQ-induced toxicity involving oxidative stress and mitochondrial dysfunction. Thus, SRT1720 might have therapeutic potential in preventing PD.
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•SIRT1 as the target of SRT1720 in mediating PQ-induced toxicities.•SRT1720 prevents PQ-induced toxicities in cellular and animal models of PD.•SRT1720 modulated PQ toxicity through PGC-1α pathway.•SRT1720 modulated PQ toxicity through NRF2 pathway.
Purpose
Most of the investigations into laser-assisted skin permeation have used the intact skin as the permeation barrier. Whether the laser is effective in improving cutaneous delivery via ...barrier-defective skin is still unclear.
Methods
In this study, ablative (Er:YAG) and non-ablative (Er:glass) lasers were examined for the penetration of peptide and siRNA upon topical application on
in vitro
skin with a healthy or disrupted barrier.
Results
An enhanced peptide flux (6.9 fold) was detected after tape stripping of the pig stratum corneum (SC). A further increase of flux to 11.7 fold was obtained after Er:YAG laser irradiation of the SC-stripped skin. However, the application of Er:glass modality did not further raise the flux via the SC-stripped skin. A similar trend was observed in the case of psoriasiform skin. Conversely, the flux was enhanced 3.7 and 2.6 fold after treatment with the Er:YAG and the Er:glass laser on the atopic dermatitis (AD)-like skin. The 3-D skin structure captured by confocal microscopy proved the distribution of peptide and siRNA through the microchannels and into the surrounding tissue.
Conclusions
The fractional laser was valid for ameliorating macromolecule permeation into barrier-disrupted skin although the enhancement level was lower than that of normal skin.
Retrospective study.
To investigate the relationship between a +ve postoperative Upper Instrumented Vertebra (UIV) (≥0°) tilt angle and the risk of medial shoulder/neck and lateral shoulder imbalance ...among Lenke 1 and 2 Adolescent Idiopathic Scoliosis (AIS) patients following Posterior Spinal Fusion.
Current UIV selection strategy has poor correlation with postoperative shoulder balance. The relationship between a +ve postoperative UIV tilt angle and the risk of postoperative shoulder and neck imbalance was unknown.
One hundred thirty-six Lenke 1 and 2 AIS patients with minimum 2 years follow-up were recruited. For medial shoulder and neck balance, patients were categorized into positive (+ve) imbalance (≥+4°), balanced, or negative (-ve) imbalance (≤-4°) groups based on T1 tilt angle/Cervical Axis measurement. For lateral shoulder balance, patients were classified into +ve imbalance (≥+3°) balanced, and -ve imbalance (≤-3°) groups based on Clavicle Angle (Cla-A) measurement. Linear regression analysis identified the predictive factors for shoulder/neck imbalance. Logistic regression analysis calculated the odds ratio of shoulder/neck imbalance for patients with +ve postoperative UIV tilt angle.
Postoperative UIV tilt angle and preoperative T1 tilt angle were predictive of +ve medial shoulder imbalance. Postoperative UIV tilt angle and postoperative PT correction were predictive of +ve neck imbalance. Approximately 51.6% of patients with +ve medial shoulder imbalance had +ve postoperative UIV tilt angle. Patients with +ve postoperative UIV tilt angle had 14.9 times increased odds of developing +ve medial shoulder imbalance and 3.3 times increased odds of developing +ve neck imbalance. Postoperative UIV tilt angle did not predict lateral shoulder imbalance.
Patients with +ve postoperative UIV tilt angle had 14.9 times increased odds of developing +ve medial shoulder imbalance (T1 tilt angle ≥+4°) and 3.3 times increased odds of developing +ve neck imbalance (cervical axis ≥+4°).
4.
A 1,3-bis(carbazol-9-yl)benzene derivative (BPBC) was synthesized and its related homopolymer (PBPBC) and copolymers (P(BPBC-
-BT), P(BPBC-
-CDT), and P(BPBC-
-CDTK)) were prepared using ...electrochemical polymerization. Investigations of polymeric spectra showed that PBPBC film was grey, iron-grey, yellowish-grey, and greyish-green from the neutral to the oxidized state. P(BPBC-
-BT), P(BPBC-
-CDT), and P(BPBC-
-CDTK) films showed multicolor transitions from the reduced to the oxidized state. The transmittance change (Δ
) of PBPBC, P(BPBC-
-BT), P(BPBC-
-CDT), and P(BPBC-
-CDTK) films were 29.6% at 1040 nm, 44.4% at 1030 nm, 22.3% at 1050 nm, and 41.4% at 1070 nm. The coloration efficiency (
) of PBPBC and P(BPBC-
-CDTK) films were evaluated to be 140.3 cm
C
at 1040 nm and 283.7 cm
C
at 1070 nm, respectively. A P(BPBC-
-BT)/PEDOT electrochromic device (ECD) showed a large Δ
(36.2% at 625 nm) and a fast response time (less than 0.5 s), whereas a P(BPBC-
-CDTK)/PEDOT ECD revealed a large
(534.4 cm
C
at 610 nm) and sufficient optical circuit memory.
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