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1.
Nat Commun ; 15(1): 2953, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580662

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.


Assuntos
Insuficiência Cardíaca , Inibidores de Hidroximetilglutaril-CoA Redutases , MicroRNAs , Animais , Masculino , Camundongos , Células Endoteliais/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , MicroRNAs/metabolismo , RNA Circular/genética , Volume Sistólico/fisiologia
2.
J Exp Biol ; 227(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38584490

RESUMO

The mechanical forces experienced during movement and the time constants of muscle activation are important determinants of the durations of behaviours, which may both be affected by size-dependent scaling. The mechanics of slow movements in small animals are dominated by elastic forces and are thus quasistatic (i.e. always near mechanical equilibrium). Muscular forces producing movement and elastic forces resisting movement should scale identically (proportional to mass2/3), leaving the scaling of the time constant of muscle activation to play a critical role in determining behavioural duration. We tested this hypothesis by measuring the duration of feeding behaviours in the marine mollusc Aplysia californica whose body sizes spanned three orders of magnitude. The duration of muscle activation was determined by measuring the time it took for muscles to produce maximum force as A. californica attempted to feed on tethered inedible seaweed, which provided an in vivo approximation of an isometric contraction. The timing of muscle activation scaled with mass0.3. The total duration of biting behaviours scaled identically, with mass0.3, indicating a lack of additional mechanical effects. The duration of swallowing behaviour, however, exhibited a shallower scaling of mass0.17. We suggest that this was due to the allometric growth of the anterior retractor muscle during development, as measured by micro-computed tomography (micro-CT) scans of buccal masses. Consequently, larger A. californica did not need to activate their muscles as fully to produce equivalent forces. These results indicate that muscle activation may be an important determinant of the scaling of behavioural durations in quasistatic systems.


Assuntos
Aplysia , Músculos , Animais , Aplysia/fisiologia , Microtomografia por Raio-X , Músculos/fisiologia , Comportamento Alimentar/fisiologia , Deglutição/fisiologia
3.
Front Immunol ; 15: 1367048, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585259

RESUMO

Objective: In the defense against microorganisms like Candida albicans, macrophages recruit LC3(Microtubule-associated protein 1A/1B-light chain 3) to the periplasm, engaging in the elimination process through the formation of a single-membrane phagosome known as LC3-associated phagocytosis (LAP). Building on this, we propose the hypothesis that glucocorticoids may hinder macrophage phagocytosis of Candida glabrata by suppressing LAP, and rapamycin could potentially reverse this inhibitory effect. Methods: RAW264.7 cells were employed for investigating the immune response to Candida glabrata infection. Various reagents, including dexamethasone, rapamycin, and specific antibodies, were utilized in experimental setups. Assays, such as fluorescence microscopy, flow cytometry, ELISA (Enzyme-Linked Immunosorbent Assay), Western blot, and confocal microscopy, were conducted to assess phagocytosis, cytokine levels, protein expression, viability, and autophagy dynamics. Results: Glucocorticoids significantly inhibited macrophage autophagy, impairing the cells' ability to combat Candida glabrata. Conversely, rapamycin exhibited a dual role, initially inhibiting and subsequently promoting phagocytosis of Candida glabrata by macrophages. Glucocorticoids hinder macrophage autophagy in Candida glabrata infection by suppressing the MTOR pathway(mammalian target of rapamycin pathway), while the activation of MTOR pathway by Candida glabrata diminishes over time. Conclusion: Our study elucidates the intricate interplay between glucocorticoids, rapamycin, and macrophage autophagy during Candida glabrata infection. Understanding the implications of these interactions not only sheds light on the host immune response dynamics but also unveils potential therapeutic avenues for managing fungal infections.


Assuntos
Candida glabrata , Candidíase , Animais , Camundongos , Candida glabrata/fisiologia , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Sirolimo/farmacologia , Camundongos Endogâmicos BALB C , Autofagia , Macrófagos , Serina-Treonina Quinases TOR/metabolismo , Mamíferos
4.
Front Immunol ; 15: 1365964, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585271

RESUMO

Ex-vivo lung perfusion (EVLP) has extended the number of transplantable lungs by reconditioning marginal organs. However, EVLP is performed at 37°C without homeostatic regulation leading to metabolic wastes' accumulation in the perfusate and, as a corrective measure, the costly perfusate is repeatedly replaced during the standard of care procedure. As an interesting alternative, a hemodialyzer could be placed on the EVLP circuit, which was previously shown to rebalance the perfusate composition and to maintain lung function and viability without appearing to impact the global gene expression in the lung. Here, we assessed the biological effects of a hemodialyzer during EVLP by performing biochemical and refined functional genomic analyses over a 12h procedure in a pig model. We found that dialysis stabilized electrolytic and metabolic parameters of the perfusate but enhanced the gene expression and protein accumulation of several inflammatory cytokines and promoted a genomic profile predicting higher endothelial activation already at 6h and higher immune cytokine signaling at 12h. Therefore, epuration of EVLP with a dialyzer, while correcting features of the perfusate composition and maintaining the respiratory function, promotes inflammatory responses in the tissue. This finding suggests that modifying the metabolite composition of the perfusate by dialysis during EVLP can have detrimental effects on the tissue response and that this strategy should not be transferred as such to the clinic.


Assuntos
Transplante de Pulmão , Suínos , Animais , Perfusão/métodos , Transplante de Pulmão/métodos , Preservação de Órgãos/métodos , Diálise Renal , Pulmão/fisiologia
5.
Sci Data ; 11(1): 350, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589476

RESUMO

Maintaining sufficient cerebral oxygen metabolism is crucial for human survival, especially in challenging conditions such as high-altitudes. Human cognitive neural activity is sensitive to fluctuations in oxygen levels. However, there is a lack of publicly available datasets on human behavioural responses and cerebral dynamics assessments during the execution of conflicting tasks in natural hypoxic environments. We recruited 80 healthy new immigrant volunteers (males, aged 20 ± 2 years) and employed the Stroop cognitive conflict paradigm. After a two-week exposure to both high and low-altitudes, the behavioural performance, prefrontal oxygen levels, and electroencephalography (EEG) signals were recorded. Comparative analyses were conducted on the behavioural reaction times and accuracy during Stroop tasks, and statistical analyses of participants' prefrontal oxygen levels and EEG signals were performed. We anticipate that our open-access dataset will contribute to the development of monitoring devices and algorithms, designed specifically for measuring cerebral oxygen and EEG dynamics in populations exposed to extreme environments, particularly among individuals suffering from oxygen deficiency.


Assuntos
Altitude , Eletroencefalografia , Humanos , Masculino , Oxigênio/análise , Tempo de Reação/fisiologia , Teste de Stroop , Adulto Jovem , Emigrantes e Imigrantes
6.
Genesis ; 62(2): e23597, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38590121

RESUMO

Sensory signals detected by olfactory sensory organs are critical regulators of animal behavior. An accessory olfactory organ, the vomeronasal organ, detects cues from other animals and plays a pivotal role in intra- and inter-species interactions in mice. However, how ethologically relevant cues control mouse behavior through approximately 350 vomeronasal sensory receptor proteins largely remains elusive. The type 2 vomeronasal receptor-A4 (V2R-A4) subfamily members have been repeatedly detected from vomeronasal sensory neurons responsive to predator cues, suggesting a potential role of this receptor subfamily as a sensor for predators. This review focuses on this intriguing subfamily, delving into its receptor functions and genetic characteristics.


Assuntos
Bulbo Olfatório , Órgão Vomeronasal , Camundongos , Animais , Bulbo Olfatório/fisiologia , Células Receptoras Sensoriais/metabolismo , Órgão Vomeronasal/metabolismo
7.
Nat Commun ; 15(1): 3220, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622115

RESUMO

Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/CCDH1) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/CCDH1 activity to treat cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)-catalyzed phosphorylation-dependent cis-trans prolyl isomerization drives tumor malignancy. However, the mechanisms controlling its protein turnover remain elusive. Through proteomic screens and structural characterizations, we identify a reciprocal antagonism of PIN1-APC/CCDH1 mediated by domain-oriented phosphorylation-dependent dual interactions as a fundamental mechanism governing mitotic protein stability and cell-cycle entry. Remarkably, combined PIN1 and cyclin-dependent protein kinases (CDKs) inhibition creates a positive feedback loop of PIN1 inhibition and APC/CCDH1 activation to irreversibly degrade PIN1 and other crucial mitotic proteins, which force permanent cell-cycle exit and trigger anti-tumor immunity, translating into synergistic efficacy against triple-negative breast cancer.


Assuntos
Proteínas de Ciclo Celular , Proteômica , Ciclo Celular/fisiologia , Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Fosforilação , Estabilidade Proteica , Peptidilprolil Isomerase de Interação com NIMA/genética , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Mitose
8.
Nat Commun ; 15(1): 3221, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622129

RESUMO

The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal's exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals' investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons may bridge external and internal signals, indicating a potential connection between spatial representation and intentional states in the construction of internal navigation systems.


Assuntos
Intenção , Navegação Espacial , Masculino , Camundongos , Animais , Percepção Espacial/fisiologia , Hipocampo/fisiologia , Córtex Entorrinal , Sinais (Psicologia) , Navegação Espacial/fisiologia
9.
Transl Psychiatry ; 14(1): 190, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622130

RESUMO

Drug addiction represents a multifaceted and recurrent brain disorder that possesses the capability to create persistent and ineradicable pathological memory. Deep brain stimulation (DBS) has shown a therapeutic potential for neuropsychological disorders, while the precise stimulation targets and therapeutic parameters for addiction remain deficient. Among the crucial brain regions implicated in drug addiction, the dorsal raphe nucleus (DRN) has been found to exert an essential role in the manifestation of addiction memory. Thus, we investigated the effects of DRN DBS in the treatment of addiction and whether it might produce side effects by a series of behavioral assessments, including methamphetamine priming-induced reinstatement of drug seeking behaviors, food-induced conditioned place preference (CPP), open field test and elevated plus-maze test, and examined brain activity and connectivity after DBS of DRN. We found that high-frequency DBS of the DRN significantly lowered the CPP scores and the number of active-nosepokes in the methamphetamine-primed CPP test and the self-administration model. Moreover, both high-frequency and sham DBS group rats were able to establish significant food-induced place preference, and no significant difference was observed in the open field test and in the elevated plus-maze test between the two groups. Immunofluorescence staining and functional magnetic resonance imaging revealed that high-frequency DBS of the DRN could alter the activity and functional connectivity of brain regions related to addiction. These results indicate that high-frequency DBS of the DRN effectively inhibits methamphetamine priming-induced relapse and seeking behaviors in rats and provides a new target for the treatment of drug addiction.


Assuntos
Estimulação Encefálica Profunda , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias , Ratos , Animais , Núcleo Dorsal da Rafe , Estimulação Encefálica Profunda/métodos , Comportamento de Procura de Droga/fisiologia , Transtornos Relacionados ao Uso de Substâncias/terapia
10.
Sci Rep ; 14(1): 8701, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622193

RESUMO

Honey bees are social insects, and each colony member has unique morphological and physiological traits associated with their social tasks. Previously, we identified a long non-coding RNA from honey bees, termed Nb-1, whose expression in the brain decreases associated with the age-polyethism of workers and is detected in some neurosecretory cells and octopaminergic neurons, suggesting its role in the regulation of worker labor transition. Herein, we investigated its spatially and temporary-regulated/sex-specific expression. Nb-1 was expressed as an abundant maternal RNA during oogenesis and embryogenesis in both sexes. In addition, Nb-1 was expressed preferentially in the proliferating neuroblasts of the mushroom bodies (a higher-order center of the insect brain) in the pupal brains, suggesting its role in embryogenesis and mushroom body development. On the contrary, Nb-1 was expressed in a drone-specific manner in the pupal and adult retina, suggesting its role in the drone visual development and/or sense. Subcellular localization of Nb-1 in the brain during development differed depending on the cell type. Considering that Nb-1 is conserved only in Apidae, our findings suggest that Nb-1 potentially has pleiotropic functions in the expression of multiple developmental, behavioral, and physiological traits, which are closely associated with the honey bee lifecycle.


Assuntos
RNA Longo não Codificante , Feminino , Masculino , Abelhas/genética , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Nióbio , Encéfalo/fisiologia , Neurônios/fisiologia , Cabeça , Pupa
11.
Sci Rep ; 14(1): 8689, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622189

RESUMO

We recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in patients with Parkinson's disease compared to age- and sex-matched healthy controls. Since both groups showed substantial inter-individual variations, we extended the cohort of controls with a group of young individuals to investigate possible age-related effects. Seventeen healthy young subjects aged < 30 years and 17 elderly subjects aged > 50 years underwent serial PC-MRI to measure the postprandial blood flow response in the SMA after ingestion of a standardized liquid test meal (∼400 kcal). Postprandial blood flow dynamics in SMA did not differ between young and elderly subjects. A noticeable inter-individual variation in postprandial intestinal blood flow increase was found, and approximately 30% of the variation could be explained by the preprandial blood flow. Regardless of age, some subjects showed a remarkable transient SMA blood flow increase immediately after meal intake. This study provides tentative evidence that postprandial blood flow dynamics in SMA in healthy young and elderly subjects do not substantially differ, indicating that age is without impact on vascular response in SMA as an indicator for regulation of mesenteric perfusion in response to food intake.


Assuntos
Hemodinâmica , Artéria Mesentérica Superior , Idoso , Humanos , Artéria Mesentérica Superior/diagnóstico por imagem , Imageamento por Ressonância Magnética , Mesentério , Período Pós-Prandial/fisiologia
12.
Sci Rep ; 14(1): 8707, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622201

RESUMO

In this study, we explored spatial-temporal dependencies and their impact on the tactile perception of moving objects. Building on previous research linking visual perception and human movement, we examined if an imputed motion mechanism operates within the tactile modality. We focused on how biological coherence between space and time, characteristic of human movement, influences tactile perception. An experiment was designed wherein participants were stimulated on their right palm with tactile patterns, either ambiguous (incongruent conditions) or non-ambiguous (congruent conditions) relative to a biological motion law (two-thirds power law) and asked to report perceived shape and associated confidence. Our findings reveal that introducing ambiguous tactile patterns (1) significantly diminishes tactile discrimination performance, implying motor features of shape recognition in vision are also observed in the tactile modality, and (2) undermines participants' response confidence, uncovering the accessibility degree of information determining the tactile percept's conscious representation. Analysis based on the Hierarchical Drift Diffusion Model unveiled the sensitivity of the evidence accumulation process to the stimulus's informational ambiguity and provides insight into tactile perception as predictive dynamics for reducing uncertainty. These discoveries deepen our understanding of tactile perception mechanisms and underscore the criticality of predictions in sensory information processing.


Assuntos
Percepção de Movimento , Percepção do Tato , Humanos , Tato/fisiologia , Percepção do Tato/fisiologia , Percepção Visual , Mãos/fisiologia , Movimento/fisiologia , Percepção de Movimento/fisiologia
13.
Sci Rep ; 14(1): 8678, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622206

RESUMO

This study emphasizes the phytochemical study of some locally available botanicals against maize weevils. Nine plant parts were collected from six plant species. The test plant powder (200 g) was suspended sequentially in 600 ml of petroleum ether, chloroform, acetone, methanol, and distilled water for 72 h with frequent agitation. Different concentrations of the crude extracts were applied to maize seeds at rates of 10 ml, 15 ml and 20 ml per 100 g. All treatments with different extracts at different rates of application showed significant differences (p < 0.05) in the cumulative mean percentage mortality of the maize weevil. The seed extract of Maesa lanceolata and Croton macrostachyus and the leaf extract of Clausena anisata showed cumulative percent mortality ranged 95.32-98.02% in 28 days after treatment application. There was no significant difference (p > 0.05) among all treatments for the prevention of F1 progeny emergence. In all extracts, Clausena anisata showed 100% inhibition of F1 progeny emergence. All treatments significantly reduced seed weight loss and damage. The treated maize seeds were germinated with an acceptable germination quality. In conclusion, an increased dosage of the extract resulted in significant mortality in maize weevils. The seed extracts of Maesa lanceolata and Croton macrostachyus and Clausena anisata leaf extract were observed to be the most promising botanical in protecting stored maize against maize weevil.


Assuntos
Besouros , Inseticidas , Plantas Medicinais , Gorgulhos , Animais , Gorgulhos/fisiologia , Inseticidas/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
14.
Sci Rep ; 14(1): 8686, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622214

RESUMO

On 28 March 2005, the Indonesian islands of Nias and Simeulue experienced a powerful Mw 8.6 earthquake and coseismic uplift and subsidence. In areas of coastal uplift (up to ~ 2.8 m), fringing reef coral communities were killed by exposure, while deeper corals that survived were subjected to habitats with altered runoff, sediment and nutrient regimes. Here we present time-series (2000-2009) of Mn/Ca, Y/Ca and Ba/Ca variability in massive Porites corals from Nias to assess the environmental impact of a wide range of vertical displacement (+ 2.5 m to - 0.4 m). High-resolution LA-ICP-MS measurements show that skeletal Mn/Ca increased at uplifted sites, regardless of reef type, indicating a post-earthquake increase in suspended sediment delivery. Transient and/or long-term increases in skeletal Y/Ca at all uplift sites support the idea of increased sediment delivery. Coral Mn/Ca and Ba/Ca in lagoonal environments highlight the additional influences of reef bathymetry, wind-driven sediment resuspension, and phytoplankton blooms on coral geochemistry. Together, the results show that the Nias reefs adapted to fundamentally altered hydrographic conditions. We show how centuries of repeated subsidence and uplift during great-earthquake cycles along the Sunda megathrust may have shaped the modern-day predominance of massive scleractinian corals on the West Sumatran reefs.


Assuntos
Antozoários , Terremotos , Animais , Antozoários/fisiologia , Recifes de Corais , Ecossistema , Fitoplâncton
15.
Sci Rep ; 14(1): 8651, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622233

RESUMO

In this study, the multifaceted toxicity induced by high doses of the essential trace element molybdenum in Allium cepa L. was investigated. Germination, root elongation, weight gain, mitotic index (MI), micronucleus (MN), chromosomal abnormalities (CAs), Comet assay, malondialdehyde (MDA), proline, superoxide dismutase (SOD), catalase (CAT) and anatomical parameters were used as biomarkers of toxicity. In addition, detailed correlation and PCA analyzes were performed for all parameters discussed. On the other hand, this study focused on the development of a two hidden layer deep neural network (DNN) using Matlab. Four experimental groups were designed: control group bulbs were germinated in tap water and application group bulbs were germinated with 1000, 2000 and 4000 mg/L doses of molybdenum for 72 h. After germination, root tips were collected and prepared for analysis. As a result, molybdenum exposure caused a dose-dependent decrease (p < 0.05) in the investigated physiological parameter values, and an increase (p < 0.05) in the cytogenetic (except MI) and biochemical parameter values. Molybdenum exposure induced different types of CAs and various anatomical damages in root meristem cells. Comet assay results showed that the severity of DNA damage increased depending on the increasing molybdenum dose. Detailed correlation and PCA analysis results determined significant positive and negative interactions between the investigated parameters and confirmed the relationships of these parameters with molybdenum doses. It has been found that the DNN model is in close agreement with the actual data showing the accuracy of the predictions. MAE, MAPE, RMSE and R2 were used to evaluate the effectiveness of the DNN model. Collective analysis of these metrics showed that the DNN model performed well. As a result, it has been determined once again that high doses of molybdenum cause multiple toxicity in A. cepa and the Allium test is a reliable universal test for determining this toxicity. Therefore, periodic measurement of molybdenum levels in agricultural soils should be the first priority in preventing molybdenum toxicity.


Assuntos
Allium , Molibdênio/toxicidade , Raízes de Plantas , Meristema , Cebolas/fisiologia , Aberrações Cromossômicas
16.
Sci Rep ; 14(1): 8684, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622246

RESUMO

Ciliates are powerful unicellular model organisms that have been used to elucidate fundamental biological processes. However, the high motility of ciliates presents a major challenge in studies using live-cell microscopy and microsurgery. While various immobilization methods have been developed, they are physiologically disruptive to the cell and incompatible with microscopy and/or microsurgery. Here, we describe a Simple Microfluidic Operating Room for the Examination and Surgery of Stentor coeruleus (SMORES). SMORES uses Quake valve-based microfluidics to trap, compress, and perform surgery on Stentor as our model ciliate. Compared with previous methods, immobilization by physical compression in SMORES is more effective and uniform. The mean velocity of compressed cells is 24 times less than that of uncompressed cells. The compression is minimally disruptive to the cell and is easily applied or removed using a 3D-printed pressure rig. We demonstrate cell immobilization for up to 2 h without sacrificing cell viability. SMORES is compatible with confocal microscopy and is capable of media exchange for pharmacokinetic studies. Finally, the modular design of SMORES allows laser ablation or mechanical dissection of a cell into many cell fragments at once. These capabilities are expected to enable biological studies previously impossible in ciliates and other motile species.


Assuntos
Cilióforos , Microfluídica , Salas Cirúrgicas , Cilióforos/fisiologia
17.
Sci Rep ; 14(1): 8652, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622265

RESUMO

This research explores different methodologies to modulate the effects of drowsiness on functional connectivity (FC) during resting-state functional magnetic resonance imaging (RS-fMRI). The study utilized a cohort of students (MRi-Share) and classified individuals into drowsy, alert, and mixed/undetermined states based on observed respiratory oscillations. We analyzed the FC group difference between drowsy and alert individuals after five different processing methods: the reference method, two based on physiological and a global signal regression of the BOLD time series signal, and two based on Gaussian standardizations of the FC distribution. According to the reference method, drowsy individuals exhibit higher cortico-cortical FC than alert individuals. First, we demonstrated that each method reduced the differences between drowsy and alert states. The second result is that the global signal regression was quantitively the most effective, minimizing significant FC differences to only 3.3% of the total FCs. However, one should consider the risks of overcorrection often associated with this methodology. Therefore, choosing a less aggressive form of regression, such as the physiological method or Gaussian-based approaches, might be a more cautious approach. Third and last, using the Gaussian-based methods, cortico-subcortical and intra-default mode network (DMN) FCs were significantly greater in alert than drowsy subjects. These findings bear resemblance to the anticipated patterns during the onset of sleep, where the cortex isolates itself to assist in transitioning into deeper slow wave sleep phases, simultaneously disconnecting the DMN.


Assuntos
Mapeamento Encefálico , Sono de Ondas Lentas , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Vigília , Sono , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia
18.
Sci Rep ; 14(1): 8718, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622275

RESUMO

Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation, with individual body composition influencing disease severity. Severe emphysema worsens symptoms through hyperinflation, which can be relieved by bronchoscopic lung volume reduction (BLVR). To investigate how body composition, assessed through CT scans, impacts outcomes in emphysema patients undergoing BLVR. Fully automated CT-based body composition analysis (BCA) was performed in patients with end-stage emphysema receiving BLVR with valves. Post-interventional muscle and adipose tissues were quantified, body size-adjusted, and compared to baseline parameters. Between January 2015 and December 2022, 300 patients with severe emphysema underwent endobronchial valve treatment. Significant improvements were seen in outcome parameters, which were defined as changes in pulmonary function, physical performance, and quality of life (QoL) post-treatment. Muscle volume remained stable (1.632 vs. 1.635 for muscle bone adjusted ratio (BAR) at baseline and after 6 months respectively), while bone adjusted adipose tissue volumes, especially total and pericardial adipose tissue, showed significant increase (2.86 vs. 3.00 and 0.16 vs. 0.17, respectively). Moderate to strong correlations between bone adjusted muscle volume and weaker correlations between adipose tissue volumes and outcome parameters (pulmonary function, QoL and physical performance) were observed. Particularly after 6-month, bone adjusted muscle volume changes positively corresponded to improved outcomes (ΔForced expiratory volume in 1 s [FEV1], r = 0.440; ΔInspiratory vital capacity [IVC], r = 0.397; Δ6Minute walking distance [6MWD], r = 0.509 and ΔCOPD assessment test [CAT], r = -0.324; all p < 0.001). Group stratification by bone adjusted muscle volume changes revealed that groups with substantial muscle gain experienced a greater clinical benefit in pulmonary function improvements, QoL and physical performance (ΔFEV1%, 5.5 vs. 39.5; ΔIVC%, 4.3 vs. 28.4; Δ6MWDm, 14 vs. 110; ΔCATpts, -2 vs. -3.5 for groups with ΔMuscle, BAR% < -10 vs. > 10, respectively). BCA results among patients divided by the minimal clinically important difference for forced expiratory volume of the first second (FEV1) showed significant differences in bone-adjusted muscle and intramuscular adipose tissue (IMAT) volumes and their respective changes after 6 months (ΔMuscle, BAR% -5 vs. 3.4 and ΔIMAT, BAR% -0.62 vs. 0.60 for groups with ΔFEV1 ≤ 100 mL vs > 100 mL). Altered body composition, especially increased muscle volume, is associated with functional improvements in BLVR-treated patients.


Assuntos
Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Pneumonectomia/métodos , Qualidade de Vida , Broncoscopia/métodos , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/cirurgia , Enfisema Pulmonar/etiologia , Enfisema/etiologia , Volume Expiratório Forçado/fisiologia , Composição Corporal , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Acta Neurochir (Wien) ; 166(1): 177, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622368

RESUMO

PURPOSE: In general, high levels of PEEP application is avoided in patients undergoing craniotomy to prevent a rise in ICP. But that approach would increase the risk of secondary brain injury especially in hypoxemic patients. Because the optic nerve sheath is distensible, a rise in ICP is associated with an increase in the optic nerve sheath diameter (ONSD). The cutoff value for elevated ICP assessed by ONSD is between 5.6 and 6.3 mm. We aimed to evaluate the effect of different PEEP levels on ONSD and compare the effect of different PEEP levels in patients with and without intracranial midline shift. METHODS: This prospective observational study was performed in aged 18-70 years, ASA I-III, 80 patients who were undergoing supratentorial craniotomy. After the induction of general anesthesia, the ONSD's were measured by the linear transducer from 3 mm below the globe at PEEP values of 0-5-10 cmH2O. The ONSD were compered between patients with (n = 7) and without midline shift (n = 73) at different PEEP values. RESULTS: The increases in ONSD due to increase in PEEP level were determined (p < 0.001). No difference was found in the comparison of ONSD between patients with and without midline shift in different PEEP values (p = 0.329, 0.535, 0.410 respectively). But application of 10 cmH2O PEEP in patients with a midline shift increased the mean ONSD value to 5.73 mm. This value is roughly 0.1 mm higher than the lower limit of the ONSD cutoff value. CONCLUSIONS: The ONSD in adults undergoing supratentorial tumor craniotomy, PEEP values up to 5 cmH2O, appears not to be associated with an ICP increase; however, the ONSD exceeded the cutoff for increased ICP when a PEEP of 10 cmH2O was applied in patients with midline shift.


Assuntos
Hipertensão Intracraniana , Adulto , Humanos , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/cirurgia , Nervo Óptico/cirurgia , Nervo Óptico/diagnóstico por imagem , Pressão Intracraniana/fisiologia , Ultrassonografia/efeitos adversos , Craniotomia/efeitos adversos , Respiração com Pressão Positiva/efeitos adversos
20.
J Comp Neurol ; 532(4): e25611, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38625816

RESUMO

A core component of the avian pallial cognitive network is the multimodal nidopallium caudolaterale (NCL) that is considered to be analogous to the mammalian prefrontal cortex (PFC). The NCL plays a key role in a multitude of executive tasks such as working memory, decision-making during navigation, and extinction learning in complex learning environments. Like the PFC, the NCL is positioned at the transition from ascending sensory to descending motor systems. For the latter, it sends descending premotor projections to the intermediate arcopallium (AI) and the medial striatum (MSt). To gain detailed insight into the organization of these projections, we conducted several retrograde and anterograde tracing experiments. First, we tested whether NCL neurons projecting to AI (NCLarco neurons) and MSt (NCLMSt neurons) are constituted by a single neuronal population with bifurcating neurons, or whether they form two distinct populations. Here, we found two distinct projection patterns to both target areas that were associated with different morphologies. Second, we revealed a weak topographic projection toward the medial and lateral striatum and a strong topographic projection toward AI with clearly distinguishable sensory termination fields. Third, we investigated the relationship between the descending NCL pathways to the arcopallium with those from the hyperpallium apicale, which harbors a second major descending pathway of the avian pallium. We embed our findings within a system of parallel pallio-motor loops that carry information from separate sensory modalities to different subpallial systems. Our results also provide insights into the evolution of the avian motor system from which, possibly, the song system has emerged.


Assuntos
Encéfalo , Columbidae , Animais , Columbidae/fisiologia , Córtex Cerebral/fisiologia , Corpo Estriado , Neostriado/fisiologia , Mamíferos
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