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1.
Annu Rev Cell Dev Biol ; 37: 469-493, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34242058

RESUMO

Morphogenesis is one of the most remarkable examples of biological pattern formation. Despite substantial progress in the field, we still do not understand the organizational principles responsible for the robust convergence of the morphogenesis process across scales to form viable organisms under variable conditions. Achieving large-scale coordination requires feedback between mechanical and biochemical processes, spanning all levels of organization and relating the emerging patterns with the mechanisms driving their formation. In this review, we highlight the role of mechanics in the patterning process, emphasizing the active and synergistic manner in which mechanical processes participate in developmental patterning rather than merely following a program set by biochemical signals. We discuss the value of applying a coarse-grained approach that considers the large-scale dynamics and feedback and complements the reductionist approach focused on molecular detail. A central challenge in this approach is identifying relevant coarse-grained variables and developing effective theories that can serve as a basis for an integrated framework toward understanding this remarkable pattern-formation process.


Assuntos
Morfogênese , Animais
2.
Cell ; 175(3): 877-886.e10, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30340045

RESUMO

Biological signaling networks use feedback control to dynamically adjust their operation in real time. Traditional static genetic methods such as gene knockouts or rescue experiments can often identify the existence of feedback interactions but are unable to determine what feedback dynamics are required. Here, we implement a new strategy, closed-loop optogenetic compensation (CLOC), to address this problem. Using a custom-built hardware and software infrastructure, CLOC monitors, in real time, the output of a pathway deleted for a feedback regulator. A minimal model uses these measurements to calculate and deliver-on the fly-an optogenetically enabled transcriptional input designed to compensate for the effects of the feedback deletion. Application of CLOC to the yeast pheromone response pathway revealed surprisingly distinct dynamic requirements for three well-studied feedback regulators. CLOC, a marriage of control theory and traditional genetics, presents a broadly applicable methodology for defining the dynamic function of biological feedback regulators.


Assuntos
Retroalimentação Fisiológica , Regulação Fúngica da Expressão Gênica , Optogenética/métodos , Teste de Complementação Genética/métodos , Fator de Acasalamento/genética , Fator de Acasalamento/metabolismo , Saccharomyces cerevisiae/genética , Software , Ativação Transcricional
3.
Proc Natl Acad Sci U S A ; 121(15): e2315730121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38557188

RESUMO

Microdroplets are a class of soft matter that has been extensively employed for chemical, biochemical, and industrial applications. However, fabricating microdroplets with largely controllable contact-area shape and apparent contact angle, a key prerequisite for their applications, is still a challenge. Here, by engineering a type of surface with homocentric closed-loop microwalls/microchannels, we can achieve facile size, shape, and contact-angle tunability of microdroplets on the textured surfaces by design. More importantly, this class of surface topologies (with universal genus value = 1) allows us to reveal that the conventional Gibbs equation (widely used for assessing the edge effect on the apparent contact angle of macrodroplets) seems no longer applicable for water microdroplets or nanodroplets (evidenced by independent molecular dynamics simulations). Notably, for the flat surface with the intrinsic contact angle ~0°, we find that the critical contact angle on the microtextured counterparts (at edge angle 90°) can be as large as >130°, rather than 90° according to the Gibbs equation. Experiments show that the breakdown of the Gibbs equation occurs for microdroplets of different types of liquids including alcohol and hydrocarbon oils. Overall, the microtextured surface design and topological wetting states not only offer opportunities for diverse applications of microdroplets such as controllable chemical reactions and low-cost circuit fabrications but also provide testbeds for advancing the fundamental surface science of wetting beyond the Gibbs equation.

4.
Mol Cell ; 72(4): 727-738.e5, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30415950

RESUMO

mRNAs form ribonucleoprotein complexes (mRNPs) by association with proteins that are crucial for mRNA metabolism. While the mRNP proteome has been well characterized, little is known about mRNP organization. Using a single-molecule approach, we show that mRNA conformation changes depending on its cellular localization and translational state. Compared to nuclear mRNPs and lncRNPs, association with ribosomes decompacts individual mRNAs, while pharmacologically dissociating ribosomes or sequestering them into stress granules leads to increased compaction. Moreover, translating mRNAs rarely show co-localized 5' and 3' ends, indicating either that mRNAs are not translated in a closed-loop configuration, or that mRNA circularization is transient, suggesting that a stable closed-loop conformation is not a universal state for all translating mRNAs.


Assuntos
Precursores de RNA/fisiologia , Ribonucleoproteínas/genética , Ribonucleoproteínas/fisiologia , Éxons , Expressão Gênica/fisiologia , Células HEK293 , Humanos , Biossíntese de Proteínas/fisiologia , Precursores de RNA/genética , Splicing de RNA , Estabilidade de RNA , RNA Longo não Codificante , RNA Mensageiro/genética , RNA Mensageiro/ultraestrutura , Ribossomos , Imagem Individual de Molécula/métodos , Análise Espacial
5.
Proc Natl Acad Sci U S A ; 120(25): e2216002120, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37314933

RESUMO

We present two binary lipid-sterol membrane systems that exhibit fluid-fluid coexistence. Partial phase diagrams of binary mixtures of dimyristoylphosphatidylcholine with 25-hydroxyxholesterol and 27-hydroxycholesterol, determined from small-angle X-ray scattering and fluorescence microscopy studies, show closed-loop fluid-fluid immiscibility gaps, with the appearance of a single fluid phase both at higher and lower temperatures. Computer simulations suggest that this unusual phase behavior results from the ability of these oxysterol molecules to take different orientations in the membrane depending on the temperature.

6.
Proc Natl Acad Sci U S A ; 120(9): e2219394120, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36802437

RESUMO

Vocal fatigue is a measurable form of performance fatigue resulting from overuse of the voice and is characterized by negative vocal adaptation. Vocal dose refers to cumulative exposure of the vocal fold tissue to vibration. Professionals with high vocal demands, such as singers and teachers, are especially prone to vocal fatigue. Failure to adjust habits can lead to compensatory lapses in vocal technique and an increased risk of vocal fold injury. Quantifying and recording vocal dose to inform individuals about potential overuse is an important step toward mitigating vocal fatigue. Previous work establishes vocal dosimetry methods, that is, processes to quantify vocal fold vibration dose but with bulky, wired devices that are not amenable to continuous use during natural daily activities; these previously reported systems also provide limited mechanisms for real-time user feedback. This study introduces a soft, wireless, skin-conformal technology that gently mounts on the upper chest to capture vibratory responses associated with vocalization in a manner that is immune to ambient noises. Pairing with a separate, wirelessly linked device supports haptic feedback to the user based on quantitative thresholds in vocal usage. A machine learning-based approach enables precise vocal dosimetry from the recorded data, to support personalized, real-time quantitation and feedback. These systems have strong potential to guide healthy behaviors in vocal use.


Assuntos
Canto , Distúrbios da Voz , Voz , Humanos , Retroalimentação , Distúrbios da Voz/etiologia , Voz/fisiologia , Prega Vocal/fisiologia
7.
Proc Natl Acad Sci U S A ; 120(15): e2301009120, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37011185

RESUMO

In the state-of-the-art membrane industry, membranes have linear life cycles and are commonly disposed of by landfill or incineration, sacrificing their sustainability. To date, little or no thought is given in the design phase to the end-of-life management of membranes. For the first time, we have innovated high-performance sustainable membranes, which can be closed-loop recycled after long-term usage for water purification. By synergizing membrane technology and dynamic covalent chemistry, covalent adaptable networks (CANs) with thermally reversible Diels-Alder (DA) adducts were synthesized and employed to fabricate integrally skinned asymmetric membranes via the nonsolvent-induced phase separation technique. Due to the stable and reversible features of CAN, the closed-loop recyclable membranes exhibit excellent mechanical properties and thermal and chemical stabilities as well as separation performance, which are comparable to or even higher than the state-of-the-art nonrecyclable membranes. Moreover, the used membranes can be closed-loop recycled with consistent properties and separation performance by depolymerization to remove contaminants, followed by refabrication into new membranes through the dissociation and reformation of DA adducts. This study may fill in the gaps in closed-loop recycling of membranes and inspire the advancement of sustainable membranes for a green membrane industry.

8.
Brain ; 147(2): 521-531, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796038

RESUMO

In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.


Assuntos
Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Estimulação Encefálica Profunda/métodos , Epilepsia/terapia , Convulsões/terapia , Encéfalo , Epilepsia Resistente a Medicamentos/terapia
9.
Brain ; 147(2): 505-520, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37675644

RESUMO

Mesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy in adults, is often refractory to medication and associated with hippocampal sclerosis. Deep brain stimulation represents an alternative treatment option for drug-resistant patients who are ineligible for resective brain surgery. In clinical practice, closed-loop stimulation at high frequencies is applied to interrupt ongoing seizures, yet has (i) a high incidence of false detections; (ii) the drawback of delayed seizure-suppressive intervention; and (iii) limited success in sclerotic tissue. As an alternative, low-frequency stimulation (LFS) has been explored recently in patients with focal epilepsies. In preclinical epilepsy models, hippocampal LFS successfully prevented seizures when applied continuously. Since it would be advantageous to reduce the stimulation load, we developed a protocol for on-demand LFS. Given the importance of the hippocampus for navigation and memory, we investigated potential consequences of LFS on hippocampal function. To this end, we used the intrahippocampal kainate mouse model, which recapitulates the key features of MTLE, including spontaneous seizure activity and hippocampal sclerosis. Specifically, our online detection algorithm monitored epileptiform activity in hippocampal local field potential recordings and identified short epileptiform bursts preceding focal seizure clusters, triggering hippocampal LFS to stabilize the network state. To probe behavioural performance, we tested the acute influence of LFS on anxiety-like behaviour in the light-dark box test, spatial and non-spatial memory in the object location memory and novel object recognition test, as well as spatial navigation and long-term memory in the Barnes maze. On-demand LFS was almost as effective as continuous LFS in preventing focal seizure clusters but with a significantly lower stimulation load. When we compared the behavioural performance of chronically epileptic mice to healthy controls, we found that both groups were equally mobile, but epileptic mice displayed an increased anxiety level, altered spatial learning strategy and impaired memory performance. Most importantly, with the application of hippocampal LFS before behavioural training and test sessions, we could rule out deleterious effects on cognition and even show an alleviation of deficits in long-term memory recall in chronically epileptic mice. Taken together, our findings may provide a promising alternative to current therapies, overcoming some of their major limitations, and inspire further investigation of LFS for seizure control in focal epilepsy syndromes.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Esclerose Hipocampal , Humanos , Camundongos , Animais , Convulsões , Hipocampo , Epilepsia do Lobo Temporal/terapia
10.
Proc Natl Acad Sci U S A ; 119(44): e2123428119, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36279449

RESUMO

Sleep constitutes a privileged state for new memories to reactivate and consolidate. Previous work has demonstrated that consolidation can be bolstered experimentally either via delivery of reminder cues (targeted memory reactivation [TMR]) or via noninvasive brain stimulation geared toward enhancing endogenous sleep rhythms. Here, we combined both approaches, controlling the timing of TMR cues with respect to ongoing slow-oscillation (SO) phases. Prior to sleep, participants learned associations between unique words and a set of repeating images (e.g., car) while hearing a prototypical image sound (e.g., engine starting). Memory performance on an immediate test vs. a test the next morning quantified overnight memory consolidation. Importantly, two image sounds were designated as TMR cues, with one cue delivered at SO UP states and the other delivered at SO DOWN states. A novel sound was used as a TMR control condition. Behavioral results revealed a significant reduction of overnight forgetting for words associated with UP-state TMR compared with words associated with DOWN-state TMR. Electrophysiological results showed that UP-state cueing led to enhancement of the ongoing UP state and was followed by greater spindle power than DOWN-state cueing. Moreover, UP-state (and not DOWN-state) cueing led to reinstatement of target image representations. Together, these results unveil the behavioral and mechanistic effects of delivering reminder cues at specific phases of endogenous sleep rhythms and mark an important step for the endeavor to experimentally modulate memories during sleep.


Assuntos
Consolidação da Memória , Humanos , Estimulação Acústica , Consolidação da Memória/fisiologia , Sinais (Psicologia) , Sono/fisiologia , Aprendizagem/fisiologia
11.
Diabetologia ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028360

RESUMO

AIMS/HYPOTHESIS: This study aimed to describe the relationship between breastfeeding episodes and maternal glucose levels, and to assess whether this differs with closed-loop vs open-loop (sensor-augmented pump) insulin therapy. METHODS: Infant-feeding diaries were collected at 6 weeks, 12 weeks and 24 weeks postpartum in a trial of postpartum closed-loop use in 18 women with type 1 diabetes. Continuous glucose monitoring (CGM) data were used to identify maternal glucose patterns within the 3 h of breastfeeding episodes. Generalised mixed models adjusted for breastfeeding episodes in the same woman, repeat breastfeeding episodes, carbohydrate intake, infant age at time of feeding and early pregnancy HbA1c. This was a secondary analysis of data collected during a randomised trial (ClinicalTrials.gov registration no. NCT04420728). RESULTS: CGM glucose remained above 3.9 mmol/l in the 3 h post-breastfeeding for 93% (397/427) of breastfeeding episodes. There was an overall decrease in glucose at nighttime within 3 h of breastfeeding (1.1 mmol l-1 h-1 decrease on average; p=0.009). A decrease in nighttime glucose was observed with open-loop therapy (1.2 ± 0.5 mmol/l) but was blunted with closed-loop therapy (0.4 ± 0.3 mmol/l; p<0.01, open-loop vs closed-loop). CONCLUSIONS/INTERPRETATION: There is a small decrease in glucose after nighttime breastfeeding that usually does not result in maternal hypoglycaemia; this appears to be blunted with the use of closed-loop therapy.

12.
Diabetologia ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740602

RESUMO

The role of automated insulin delivery systems in diabetes is expanding. Hybrid closed-loop systems are being used in routine clinical practice for treating people with type 1 diabetes. Encouragingly, real-world data reflects the performance and usability observed in clinical trials. We review the commercially available hybrid closed-loop systems, their distinctive features and the associated real-world data. We also consider emerging indications for closed-loop systems, including the treatment of type 2 diabetes where variability of day-to-day insulin requirements is high, and other challenging applications for this technology. We discuss issues around access and implementation of closed-loop technology, and consider the limitations of present closed-loop systems, as well as innovative approaches that are being evaluated to improve their performance.

13.
Diabetologia ; 67(7): 1235-1244, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38634887

RESUMO

AIMS/HYPOTHESIS: This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP). METHODS: This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19-69 years with type 1 diabetes who had HbA1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates. RESULTS: A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: -0.7 mmol/mol [95% CI -2.0, 0.8 mmol/mol] (-0.1% [95% CI -0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group. CONCLUSIONS/INTERPRETATION: The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0008398 FUNDING: The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056).


Assuntos
Glicemia , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Masculino , Pessoa de Meia-Idade , Adulto , Feminino , Insulina/administração & dosagem , Insulina/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Glicemia/análise , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Idoso , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/análise , República da Coreia , Automonitorização da Glicemia/métodos , Adulto Jovem
14.
Diabetologia ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967667

RESUMO

This review outlines some of the extraordinary recent advances in diabetes technology, which are transforming the management of type 1 diabetes before, during and after pregnancy. It highlights recent improvements associated with use of continuous glucose monitoring (CGM) but acknowledges that neither CGM nor insulin pump therapy are adequate for achieving the pregnancy glucose targets. Furthermore, even hybrid closed-loop (HCL) systems that are clinically effective outside of pregnancy may not confer additional benefits throughout pregnancy. To date, there is only one HCL system, the CamAPS FX, with a strong evidence base for use during pregnancy, suggesting that the pregnancy benefits are HCL system specific. This is in stark contrast to HCL system use outside of pregnancy, where benefits are HCL category specific. The CamAPS FX HCL system has a rapidly adaptive algorithm and lower glucose targets with benefits across all maternal glucose categories, meaning that it is applicable for all women with type 1 diabetes, before and during pregnancy. For women of reproductive years living with type 2 diabetes, the relative merits of using non-insulin pharmacotherapies vs diabetes technology (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) are unknown. Despite the urgent unmet need and potential benefits, studies of pharmacotherapy and technology use are extremely limited in pregnant women with type 2 diabetes.

15.
Diabetologia ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951212

RESUMO

The increasing incidence of type 2 diabetes, which represents 90% of diabetes cases globally, is a major public health concern. Improved glucose management reduces the risk of vascular complications and mortality; however, only a small proportion of the type 2 diabetes population have blood glucose levels within the recommended treatment targets. In recent years, diabetes technologies have revolutionised the care of people with type 1 diabetes, and it is becoming increasingly evident that people with type 2 diabetes can also benefit from these advances. In this review, we describe the current knowledge regarding the role of technologies for people living with type 2 diabetes and the evidence supporting their use in clinical practice. We conclude that continuous glucose monitoring systems deliver glycaemic benefits for individuals with type 2 diabetes, whether treated with insulin or non-insulin therapy; further data are required to evaluate the role of these systems in those with prediabetes (defined as impaired glucose tolerance and/or impaired fasting glucose and/or HbA1c levels between 39 mmol/mol [5.7%] and 47 mmol/mol [6.4%]). The use of insulin pumps seems to be safe and effective in people with type 2 diabetes, especially in those with an HbA1c significantly above target. Initial results from studies exploring the impact of closed-loop systems in type 2 diabetes are promising. We discuss directions for future research to fully understand the potential benefits of integrating evidence-based technology into care for people living with type 2 diabetes and prediabetes.

16.
Eur J Neurosci ; 59(3): 457-472, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38178558

RESUMO

Millions of people suffer from dopamine-related disorders spanning disturbances in movement, cognition and emotion. These changes are often attributed to changes in striatal dopamine function. Thus, understanding how dopamine signalling in the striatum and basal ganglia shapes human behaviour is fundamental to advancing the treatment of affected patients. Dopaminergic neurons innervate large-scale brain networks, and accordingly, many different roles for dopamine signals have been proposed, such as invigoration of movement and tracking of reward contingencies. The canonical circuit architecture of cortico-striatal loops sparks the question, of whether dopamine signals in the basal ganglia serve an overarching computational principle. Such a holistic understanding of dopamine functioning could provide new insights into symptom generation in psychiatry to neurology. Here, we review the perspective that dopamine could bidirectionally control neural population dynamics, increasing or decreasing their strength and likelihood to reoccur in the future, a process previously termed neural reinforcement. We outline how the basal ganglia pathways could drive strengthening and weakening of circuit dynamics and discuss the implication of this hypothesis on the understanding of motor signs of Parkinson's disease (PD), the most frequent dopaminergic disorder. We propose that loss of dopamine in PD may lead to a pathological brain state where repetition of neural activity leads to weakening and instability, possibly explanatory for the fact that movement in PD deteriorates with repetition. Finally, we speculate on how therapeutic interventions such as deep brain stimulation may be able to reinstate reinforcement signals and thereby improve treatment strategies for PD in the future.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Humanos , Dopamina/metabolismo , Gânglios da Base , Encéfalo/metabolismo
17.
Eur J Neurosci ; 59(4): 613-640, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37675803

RESUMO

Closed-loop auditory stimulation (CLAS) is a brain modulation technique in which sounds are timed to enhance or disrupt endogenous neurophysiological events. CLAS of slow oscillation up-states in sleep is becoming a popular tool to study and enhance sleep's functions, as it increases slow oscillations, evokes sleep spindles and enhances memory consolidation of certain tasks. However, few studies have examined the specific neurophysiological mechanisms involved in CLAS, in part because of practical limitations to available tools. To evaluate evidence for possible models of how sound stimulation during brain up-states alters brain activity, we simultaneously recorded electro- and magnetoencephalography in human participants who received auditory stimulation across sleep stages. We conducted a series of analyses that test different models of pathways through which CLAS of slow oscillations may affect widespread neural activity that have been suggested in literature, using spatial information, timing and phase relationships in the source-localized magnetoencephalography data. The results suggest that auditory information reaches ventral frontal lobe areas via non-lemniscal pathways. From there, a slow oscillation is created and propagated. We demonstrate that while the state of excitability of tissue in auditory cortex and frontal ventral regions shows some synchrony with the electroencephalography (EEG)-recorded up-states that are commonly used for CLAS, it is the state of ventral frontal regions that is most critical for slow oscillation generation. Our findings advance models of how CLAS leads to enhancement of slow oscillations, sleep spindles and associated cognitive benefits and offer insight into how the effectiveness of brain stimulation techniques can be improved.


Assuntos
Magnetoencefalografia , Sono , Humanos , Estimulação Acústica , Sono/fisiologia , Eletroencefalografia/métodos , Encéfalo/fisiologia
18.
Microbiology (Reading) ; 170(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39016549

RESUMO

In recent years, the demand for lithium-ion batteries (LIBs) has been increasing rapidly. Conventional recycling strategies (based on pyro- and hydrometallurgy) are damaging for the environment and more sustainable methods need to be developed. Bioleaching is a promising environmentally friendly approach that uses microorganisms to solubilize metals. However, a bioleaching-based technology has not yet been applied to recover valuable metals from waste LIBs on an industrial scale. A series of experiments was performed to improve metal recovery rates from an active cathode material (LiCoO2; LCO). (i) Direct bioleaching of ≤0.5 % LCO with two prokaryotic acidophilic consortia achieved >80 % Co and 90 % Li extraction. Significantly lower metal recovery rates were obtained at 30 °C than at 45 °C. (ii) In contrast, during direct bioleaching of 3 % LCO with consortia adapted to elevated LCO levels, the 30 °C consortium performed significantly better than the 45 °C consortium, solubilizing 73 and 93 % of the Co and Li, respectively, during one-step bioleaching, and 83 and 99 % of the Co and Li, respectively, during a two-step process. (iii) The adapted 30°C consortium was used for indirect leaching in a low-waste closed-loop system (with 10 % LCO). The process involved generation of sulfuric acid in an acid-generating bioreactor (AGB), 2-3 week leaching of LCO with the biogenic acid (pH 0.9), selective precipitation of Co as hydroxide, and recirculation of the metal-free liquor back into the AGB. In total, 58.2 % Co and 100 % Li were solubilized in seven phases, and >99.9 % of the dissolved Co was recovered after each phase as a high-purity Co hydroxide. Additionally, Co nanoparticles were generated from the obtained Co-rich leachates, using Desulfovibrio alaskensis, and Co electrowinning was optimized as an alternative recovery technique, yielding high recovery rates (91.1 and 73.6% on carbon felt and roughened steel, respectively) from bioleachates that contained significantly lower Co concentrations than industrial hydrometallurgical liquors. The closed-loop system was highly dominated by the mixotrophic archaeon Ferroplasma and sulfur-oxidizing bacteria Acidithiobacillus caldus and Acidithiobacillus thiooxidans. The developed system achieved high metal recovery rates and provided high-purity solid products suitable for a battery supply chain, while minimizing waste production and the inhibitory effects of elevated concentrations of dissolved metals on the leaching prokaryotes. The system is suitable for scale-up applications and has the potential to be adapted to different battery chemistries.


Assuntos
Cobalto , Fontes de Energia Elétrica , Eletrodos , Lítio , Lítio/química , Cobalto/química , Biotecnologia/métodos , Reciclagem , Bactérias/metabolismo , Bactérias/genética
19.
Small ; 20(12): e2307072, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37940616

RESUMO

Discovering new deep ultraviolet (DUV) nonlinear optical (NLO) materials is the current research hotspot. However, how to perfectly integrate several stringent performances into a crystal is a great challenge because of the natural incompatibility among them, particularly wide band gap and large NLO coefficient. To tackle the challenge, a boron-rich closed-loop strategy is supposed, based on which a new barium borate, Ba4B14O25, is designed and synthesized successfully via the high-temperature solid-state melting method. It features a highly polymeric 3D geometry with the closed-loop anionic framework [B14O25]8- constructed by the fundamental building blocks [B14O33]24-. The high-density π-conjugated [BO3]3- groups and the fully closed-loop B-O-B connections make Ba4B14O25 possess excellent NLO properties, including short UV cutoff edge (<200 nm), large second harmonic generation response (3.0 × KDP) and phase-matching capability, being a promising DUV-transparent NLO candidate material. The work provides a creative design strategy for the exploration of DUV NLO crystals.

20.
Small ; 20(26): e2309429, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38553811

RESUMO

Thermally driven fiber actuators are emerging as promising tools for a range of robotic applications, encompassing soft and wearable robots, muscle function restoration, assistive systems, and physical augmentation. Yet, to realize their full potential in practical applications, several challenges, such as a high operational temperature, incorporation of intrinsic self-sensing capabilities for closed-loop feedback control, and reliance on bulky, intricate actuation systems, must be addressed. Here, an Ag nanoparticles-based twisted and coiled fiber actuator that achieves a high contractile actuation of ≈36% is reported at a considerably low operational temperature of ≈83 °C based on a synergistic effect of constituent fiber elements with low glass transition temperatures. The fiber actuator can monitor its contractile actuation in real-time based on the piezoresistive properties inherent to its Ag-based conductive region, demonstrating its proprioceptive sensing capability. By exploiting this capability, the proprioceptive fiber actuator adeptly maintains its intended contractile behavior, even when faced with unplanned external disturbances. To demonstrate the capabilities of the fiber actuator, this study integrates it into a closed-loop feedback-controlled bionic arm as an artificial muscle, offering fresh perspectives on the future development of intelligent wearable devices and soft robotic systems.

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