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1.
Nature ; 603(7901): 427-433, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35296847

RESUMO

Plants cover a large fraction of the Earth's land mass despite most species having limited to no mobility. To transport their propagules, many plants have evolved mechanisms to disperse their seeds using the wind1-4. A dandelion seed, for example, has a bristly filament structure that decreases its terminal velocity and helps orient the seed as it wafts to the ground5. Inspired by this, we demonstrate wind dispersal of battery-free wireless sensing devices. Our millimetre-scale devices weigh 30 milligrams and are designed on a flexible substrate using programmable, off-the-shelf parts to enable scalability and flexibility for various sensing and computing applications. The system is powered using lightweight solar cells and an energy harvesting circuit that is robust to low and variable light conditions, and has a backscatter communication link that enables data transmission. To achieve the wide-area dispersal and upright landing that is necessary for solar power harvesting, we developed dandelion-inspired, thin-film porous structures that achieve a terminal velocity of 0.87 ± 0.02 metres per second and aerodynamic stability with a probability of upright landing of over 95%. Our results in outdoor environments demonstrate that these devices can travel 50-100 metres in gentle to moderate breeze. Finally, in natural systems, variance in individual seed morphology causes some seeds to fall closer and others to travel farther. We adopt a similar approach and show how we can modulate the porosity and diameter of the structures to achieve dispersal variation across devices.


Assuntos
Taraxacum , Vento , Porosidade , Sementes/anatomia & histologia
2.
Proc Natl Acad Sci U S A ; 120(11): e2210439120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36897982

RESUMO

How does neural activity drive muscles to produce behavior? The recent development of genetic lines in Hydra that allow complete calcium imaging of both neuronal and muscle activity, as well as systematic machine learning quantification of behaviors, makes this small cnidarian an ideal model system to understand and model the complete transformation from neural firing to body movements. To achieve this, we have built a neuromechanical model of Hydra's fluid-filled hydrostatic skeleton, showing how drive by neuronal activity activates distinct patterns of muscle activity and body column biomechanics. Our model is based on experimental measurements of neuronal and muscle activity and assumes gap junctional coupling among muscle cells and calcium-dependent force generation by muscles. With these assumptions, we can robustly reproduce a basic set of Hydra's behaviors. We can further explain puzzling experimental observations, including the dual timescale kinetics observed in muscle activation and the engagement of ectodermal and endodermal muscles in different behaviors. This work delineates the spatiotemporal control space of Hydra movement and can serve as a template for future efforts to systematically decipher the transformations in the neural basis of behavior.


Assuntos
Hydra , Animais , Hydra/fisiologia , Cálcio , Músculos , Movimento
3.
PLoS Pathog ; 18(11): e1010924, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36383559

RESUMO

Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. Here, erythrocytes infected by late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. Immunity to placental malaria is acquired through exposure and mediated through antibodies to VAR2CSA. Through evolution, the VAR2CSA proteins have diversified in sequence to escape immune recognition but retained their overall macromolecular structure to maintain CS binding affinity. This structural conservation may also have allowed development of broadly reactive antibodies to VAR2CSA in immune women. Here we show the negative stain and cryo-EM structure of the only known broadly reactive human monoclonal antibody, PAM1.4, in complex with VAR2CSA. The data shows how PAM1.4's broad VAR2CSA reactivity is achieved through interactions with multiple conserved residues of different sub-domains forming conformational epitope distant from the CS binding site on the VAR2CSA core structure. Thus, while PAM1.4 may represent a class of antibodies mediating placental malaria immunity by inducing phagocytosis or NK cell-mediated cytotoxicity, it is likely that broadly CS binding-inhibitory antibodies target other epitopes at the CS binding site. Insights on both types of broadly reactive monoclonal antibodies may aid the development of a vaccine against placental malaria.


Assuntos
Malária Falciparum , Malária , Humanos , Feminino , Gravidez , Antígenos de Protozoários , Malária Falciparum/parasitologia , Epitopos , Anticorpos Antiprotozoários , Anticorpos Monoclonais , Microscopia Crioeletrônica , Placenta/metabolismo , Plasmodium falciparum/metabolismo , Eritrócitos/parasitologia , Sulfatos de Condroitina/metabolismo
4.
Blood ; 140(19): 2063-2075, 2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-36040436

RESUMO

Studies have shown significantly increased thromboembolic events at high altitude. We recently reported that transferrin could potentiate blood coagulation, but the underlying mechanism for high altitude-related thromboembolism is still poorly understood. Here, we examined the activity and concentration of plasma coagulation factors and transferrin in plasma collected from long-term human residents and short-stay mice exposed to varying altitudes. We found that the activities of thrombin and factor XIIa (FXIIa) along with the concentrations of transferrin were significantly increased in the plasma of humans and mice at high altitudes. Furthermore, both hypoxia (6% O2) and low temperature (0°C), 2 critical high-altitude factors, enhanced hypoxia-inducible factor 1α (HIF-1α) levels to promote the expression of the transferrin gene, whose enhancer region contains HIF-1α binding site, and consequently, to induce hypercoagulability by potentiating thrombin and FXIIa. Importantly, thromboembolic disorders and pathological insults in mouse models induced by both hypoxia and low temperature were ameliorated by transferrin interferences, including transferrin antibody treatment, transferrin downregulation, and the administration of our designed peptides that inhibit the potentiation of transferrin on thrombin and FXIIa. Thus, low temperature and hypoxia upregulated transferrin expression-promoted hypercoagulability. Our data suggest that targeting the transferrin-coagulation pathway is a novel and potentially powerful strategy against thromboembolic events caused by harmful environmental factors under high-altitude conditions.


Assuntos
Altitude , Trombofilia , Camundongos , Humanos , Animais , Transferrina/genética , Trombina/metabolismo , Temperatura , Hipóxia/metabolismo , Trombofilia/etiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
5.
Trop Med Int Health ; 29(3): 243-255, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38191232

RESUMO

OBJECTIVES: Anaemia during pregnancy is a major health challenge affecting pregnancy outcome worldwide. The objectives of this study were to investigate the impact of severe-moderate anaemia in the first trimester, as well as changes in haemoglobin during pregnancy among non-anaemic women, on foetal weight, placental blood flow and newborn anthropometrics. METHODS: In a prospective cohort study, 346 women residing in rural Tanzania were followed throughout pregnancy with serial ultrasound and newborn anthropometrics assessed within 24 h of delivery. Associations between placental blood flow, foetal weight and newborn anthropometrics with either first trimester severe-moderate anaemia (haemoglobin≤9.5 g/dL) or changes in haemoglobin from the first to the third trimester among non-anaemic women, were assessed by mixed model regression and multiple linear regression, adjusting for maternal and foetal co-variables. Foetal weights and birthweight were converted to z-scores using a population based sex-specific weight reference. RESULTS: Severe-moderate anaemia in the first trimester was associated with significantly reduced foetal weight z-scores (adjusted mean difference (aMD) -0.44 (95% CI -0.81, -0.07)) and newborn anthropometric indices (birth weight z-score aMD -0.55 (-0.9, -0.13), abdominal circumference aMD -11 mm (95% CI -20, -3)). There were no association between first trimester severe-moderate anaemia and placental blood flow. Among women who were non-anaemic in the first trimester, women with the least reduction in haemoglobin (Δ ≥ -0.3 g/dL) delivered significantly smaller newborns (birthweight z-score aMD -0.55 (-0.91, -0.20), abdominal circumference aMD -10 mm (95% CI -17, -3), compared to women with the greatest reduction (Δ haemoglobin ≤ -1.4 g/dL)). CONCLUSIONS: Severe-moderate anaemia in early pregnancy was associated with smaller newborn anthropometrics which was reflected in smaller mean foetal weights in the second and third trimester. Furthermore, among women who were non-anaemic in the first trimester, there was an association between smaller newborn anthropometrics and limited haemoglobin decrease during pregnancy, possibly reflecting insufficient plasma expansion.


Assuntos
Anemia , Complicações Hematológicas na Gravidez , Gravidez , Feminino , Recém-Nascido , Humanos , Primeiro Trimestre da Gravidez , Peso Fetal , Peso ao Nascer , Estudos Prospectivos , Tanzânia/epidemiologia , Complicações Hematológicas na Gravidez/epidemiologia , Placenta , Anemia/epidemiologia , Resultado da Gravidez/epidemiologia , Hemoglobinas , Estudos de Coortes
6.
Med Educ ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38868914

RESUMO

CONTEXT: One central consideration in health professions education (HPE) is to ensure we are making sound and justifiable decisions based on the assessment instruments we use on health professionals. To achieve this goal, HPE assessment researchers have drawn on Kane's argument-based framework to ascertain the validity of their assessment tools. However, the original four-inference model proposed by Kane - frequently used in HPE validation research - has its limitations in terms of what each inference entails and what claims and sources of backing are housed in each inference. The under-specification in the four-inference model has led to inconsistent practices in HPE validation research, posing challenges for (i) researchers who want to evaluate the validity of different HPE assessment tools and/or (ii) researchers who are new to test validation and need to establish a coherent understanding of argument-based validation. METHODS: To address these identified concerns, this article introduces the expanded seven-inference argument-based validation framework that is established practice in the field of language testing and assessment (LTA). We explicate (i) why LTA researchers experienced the need to further specify the original four Kanean inferences; (ii) how LTA validation research defines each of their seven inferences and (iii) what claims, assumptions and sources of backing are associated with each inference. Sampling six representative validation studies in HPE, we demonstrate why an expanded model and a shared disciplinary validation framework can facilitate the examination of the validity evidence in diverse HPE validation contexts. CONCLUSIONS: We invite HPE validation researchers to experiment with the seven-inference argument-based framework from LTA to evaluate its usefulness to HPE. We also call for greater interdisciplinary dialogue between HPE and LTA since both disciplines share many fundamental concerns about language use, communication skills, assessment practices and validity in assessment instruments.

7.
Facial Plast Surg ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38806160

RESUMO

The surgical net technique, originally conceptualized to mitigate postoperative hematomas, has evolved into a versatile tool, transcending its initial purpose, and signaling a new era of surgical innovation. This article provides a comprehensive overview of the surgical net's journey from a targeted solution to a multifaceted surgical asset and explores its burgeoning applications, challenges, and future trajectories. Despite early reluctance due to anatomical concerns and unfamiliarity with the novel technique, the surgical net's consistent success in various surgical contexts from facial surgeries to gynecological applications has catalyzed its widespread global adoption. The technique's integration of the progressive tension method and enhanced skin redraping capabilities underscores its contribution to optimal aesthetic outcomes and improved surgical control. Noteworthy is its role in the innovative concept of gliding surgery, marked by procedures like the gliding brow lift and Glidelift, demonstrating the surgical net's adaptability and effectiveness in diverse surgical environments.Contributions from international surgeons have expanded its applications to areas like axillary space obliteration after breast implant, postmastectomy closure, and the management of postpartum hemorrhage, showcasing the surgical net's global impact and universal commitment to optimizing surgical outcomes. The article delves into the anatomical considerations essential for adapting the surgical net technique to various surgical contexts, emphasizing the need for continuous research, clinical trials, and multidisciplinary collaboration to navigate emerging challenges and ensure its sustained efficacy and safety.In conclusion, the article highlights the surgical net technique's unwavering potential for further advancements, greater procedural efficiency, and the continued elevation of patient care standards. The consistent evolution of its applications, paired with a dedicated approach to addressing emergent challenges, reinforces the surgical net's enduring contribution to surgical innovation and global patient welfare.

8.
Br J Haematol ; 200(6): 776-791, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36341698

RESUMO

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting infants and children. Activated platelets predispose patients to coronary artery structural lesions that may lead to thrombotic cardiovascular events. To discover potential proteins underlying platelet activation in KD, we conducted a protein chip assay of 34 cytokines and discovered thymic stromal lymphopoietin (TSLP) was aberrantly expressed, which remained elevated after intravenous immunoglobulin G (IVIG) treatment and during convalescence in KD patients in comparison to healthy controls. Enzyme-linked immunosorbent assay (ELISA) corroborated the upregulation of TSLP in KD patients, which was exacerbated in convalescent patients complicated with thrombosis. TSLP receptors on platelets were also significantly upregulated in KD patients complicated with thrombosis. Platelet activation, apoptosis, and mitochondrial autophagy (mitophagy) were increased in convalescence KD patients complicated with thrombosis. In vitro, TSLP induced platelet activation and platelet mitophagy in healthy blood donors, as observed in KD patients. TSLP, similar to mitophagy agonist carbonyl cyanide 3-chlorophenyl hydrazone (CCCP), promoted thrombosis, which was attenuated by the mitophagy inhibitor Mdivi-1. Co-immunoprecipitation in TSLP-treated platelets revealed TSLP receptor (TSLPR) bound to mitophagy regulators, Parkin and Voltage Dependent Anion Channel Protein 1 (VDAC1).Thus, our results demonstrated that TSLP induced platelet mitophagy via a novel TSLPR/Parkin/VDAC1 pathway that promoted thrombosis in KD. These results suggest TSLP as a novel therapeutic target against KD-associated thrombosis.


Assuntos
Plaquetas , Síndrome de Linfonodos Mucocutâneos , Lactente , Criança , Humanos , Plaquetas/metabolismo , Linfopoietina do Estroma do Timo , Mitofagia , Síndrome de Linfonodos Mucocutâneos/terapia , Convalescença , Citocinas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
9.
PLoS Comput Biol ; 18(9): e1010512, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36166481

RESUMO

Insect flight is a strongly nonlinear and actuated dynamical system. As such, strategies for understanding its control have typically relied on either model-based methods or linearizations thereof. Here we develop a framework that combines model predictive control on an established flight dynamics model and deep neural networks (DNN) to create an efficient method for solving the inverse problem of flight control. We turn to natural systems for inspiration since they inherently demonstrate network pruning with the consequence of yielding more efficient networks for a specific set of tasks. This bio-inspired approach allows us to leverage network pruning to optimally sparsify a DNN architecture in order to perform flight tasks with as few neural connections as possible, however, there are limits to sparsification. Specifically, as the number of connections falls below a critical threshold, flight performance drops considerably. We develop sparsification paradigms and explore their limits for control tasks. Monte Carlo simulations also quantify the statistical distribution of network weights during pruning given initial random weights of the DNNs. We demonstrate that on average, the network can be pruned to retain a small amount of original network weights and still perform comparably to its fully-connected counterpart. The relative number of remaining weights, however, is highly dependent on the initial architecture and size of the network. Overall, this work shows that sparsely connected DNNs are capable of predicting the forces required to follow flight trajectories. Additionally, sparsification has sharp performance limits.


Assuntos
Insetos , Redes Neurais de Computação , Animais
10.
CMAJ ; 195(20): E699-E708, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37220929

RESUMO

BACKGROUND: Cannabis use during pregnancy is increasing, but the contribution of cannabis legalization to these trends is unclear. We sought to determine whether health service utilization related to cannabis use during pregnancy increased after the legalization of nonmedical cannabis in October 2018 in Ontario, Canada. METHODS: In this population-based, repeated cross-sectional study, we evaluated changes in the number of pregnant people who received acute care (emergency department visit or admission to hospital) between January 2015 and July 2021 among all people eligible for the province's public health coverage. We used segmented regression to compare changes in the quarterly rate of pregnant people with acute care related to cannabis use (primary outcome) with the quarterly rates of acute care for mental health conditions or for noncannabis substance use (control conditions). We identified risk factors associated with acute care for cannabis use and the risk of adverse neonatal outcomes using multivariable logistic regression models. RESULTS: The mean quarterly rate of acute care for cannabis use during pregnancy increased from 11.0 per 100 000 pregnancies before legalization to 20.0 per 100 000 pregnancies after legalization (incidence rate ratio [IRR] 1.82, 95% confidence interval [CI] 1.44-2.31), while acute care for mental health conditions decreased (IRR 0.86, 95% CI 0.78-0.95) and acute care for noncannabis substance use did not change (IRR 1.03, 95% CI 0.91-1.17). Legalization was not associated with an immediate change, but the quarterly change in rates of pregnancies with acute care for cannabis use increased by 1.13 (95% CI 0.46-1.79) per 100 000 pregnancies after legalization. Pregnant people with acute care for cannabis use had greater odds of having received acute care for hyperemesis gravidarum during their pregnancy than those without acute care for cannabis use (30.9% v. 2.5%, adjusted odds ratio [OR] 9.73, 95% CI 8.01-11.82). Pregnancies with acute care for cannabis use had greater odds of newborns being born preterm (16.9% v. 7.2%, adjusted OR 1.93, 95% CI 1.45-2.56) and of requiring care in the neonatal intensive care unit (31.5% v. 13.0%, adjusted OR 1.94 95% CI 1.54-2.44) than those without acute care for cannabis use. INTERPRETATION: The rate of acute care related to cannabis use during pregnancy almost doubled after legalization of nonmedical cannabis, although absolute increases were small. These findings highlight the need to consider interventions to reduce cannabis use during pregnancy in jurisdictions pursuing legalization.


Assuntos
Cannabis , Alucinógenos , Recém-Nascido , Feminino , Gravidez , Humanos , Ontário , Estudos Transversais , Cuidados Críticos
11.
BMC Med Educ ; 23(1): 304, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37131174

RESUMO

BACKGROUND: Curriculum revision in healthcare programs occurs frequently, but to undergo a whole degree transformation is less common. Also, the outcomes of curriculum redesign interventions on the selfreported clinical decision making, experiences, and perceptions of graduates of health education programs is unclear. This study evaluated these factors as an outcome of a pharmacy degree whole-curriculum transformation. METHODS: A 25-item cross-sectional end-of-course survey was developed to evaluate pharmacy student decisions, experiences, and perceptions upon completion of degree, pre- and post- curriculum transformation. A two-way analysis of variance (ANOVA) was used to determine whether the responses to the items classed within the main factors differed across the two cohorts. Independent t-tests were used to examine the student responses to the individual questions between the two cohorts. RESULTS: Graduates from the transformed degree had greater self-efficacy in clinical activities, were more satisfied with their education, found course activities more useful, and were more confident in their career choice. Transformed pharmacy degree students also reported spending more time on weekdays and weekends on activities such as attending lectures and working. Student satisfaction with their choice to attend pharmacy school was also significantly higher in transformed degree students. CONCLUSIONS: Responses to the end of degree survey indicate that students who completed the transformed pharmacy curriculum have had positive experiences throughout their degree and felt more prepared for practice as pharmacists in comparison to students who completed the established degree. These results add value to those collected from other sources (e.g., student evaluations, assessment scores, preceptors focus groups, and other stakeholder inputs) consistent with a comprehensive quality improvement model.


Assuntos
Educação em Farmácia , Estudantes de Farmácia , Humanos , Escolha da Profissão , Autoeficácia , Farmacêuticos , Estudos Transversais , Inquéritos e Questionários , Educação em Farmácia/métodos , Currículo , Satisfação Pessoal
12.
Aesthet Surg J ; 43(6): 623-630, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36636947

RESUMO

BACKGROUND: The hemostatic net, which was initially described as a method to decrease hematoma rates in facelift and necklift procedures, has since increased in practice and applicability. However, despite its demonstrated safety and efficacy, there exists significant skepticism with regard to its necessity; in particular, there is concern that the transcutaneous sutures may restrict dermal perfusion. OBJECTIVES: The goal of this study was to assess flap perfusion, both before and after application of the hemostatic net, to determine if there was an objective decrease in tissue perfusion in relation to application of the hemostatic net, as measured by laser-assisted angiography (LAA). METHODS: Eight patients underwent cervicofacial flap reconstruction of cutaneous malignancy defects, after which a hemostatic net was applied. All patients underwent evaluation with LAA both before and after application of the net. The average relative and absolute perfusion of different zones of the flap were calculated. RESULTS: The average absolute change in relative perfusion was +6.41%, +0.31%, and +3.28% for zones 1, 2, and 3, respectively, after application of the hemostatic net. There was no statistical difference in relative tissue perfusion after application of the net. There were no instances of delayed healing, infections, ischemia, necrosis, or hematoma. One patient developed a seroma after the net was removed. No patients had scarring or residual track marks from the transcutaneous sutures. CONCLUSIONS: With LAA, we were able to objectively demonstrate no significant decrease in tissue perfusion after the application of the hemostatic net.


Assuntos
Hemostáticos , Humanos , Angiofluoresceinografia , Verde de Indocianina , Lasers , Software , Hematoma
13.
Blood ; 136(8): 974-988, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32584951

RESUMO

Several adaptor molecules bind to cytoplasmic tails of ß-integrins and facilitate bidirectional signaling, which is critical in thrombosis and hemostasis. Interfering with integrin-adaptor interactions spatially or temporally to inhibit thrombosis without affecting hemostasis is an attractive strategy for the development of safe antithrombotic drugs. We show for the first time that the 14-3-3ζ-c-Src-integrin-ß3 complex is formed during platelet activation. 14-3-3ζ-c-Src interaction is mediated by the -PIRLGLALNFSVFYYE- fragment (PE16) on the 14-3-3ζ and SH2-domain on c-Src, whereas the 14-3-3ζ-integrin-ß3 interaction is mediated by the -ESKVFYLKMKGDYYRYL- fragment (EL17) on the 14-3-3ζ and -KEATSTF- fragment (KF7) on the ß3-integrin cytoplasmic tail. The EL17-motif inhibitor, or KF7 peptide, interferes with the formation of the 14-3-3ζ-c-Src-integrin-ß3 complex and selectively inhibits ß3 outside-in signaling without affecting the integrin-fibrinogen interaction, which suppresses thrombosis without causing significant bleeding. This study characterized a previously unidentified 14-3-3ζ-c-Src-integrin-ß3 complex in platelets and provided a novel strategy for the development of safe and effective antithrombotic treatments.


Assuntos
Proteínas 14-3-3/metabolismo , Integrina beta3/metabolismo , Ativação Plaquetária , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Proteínas 14-3-3/genética , Adulto , Animais , Feminino , Células HEK293 , Humanos , Integrina beta3/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Complexos Multiproteicos/metabolismo , Complexos Multiproteicos/fisiologia , Ativação Plaquetária/genética , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Transdução de Sinais/fisiologia
14.
PLoS Comput Biol ; 17(8): e1009195, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34379622

RESUMO

Animals rely on sensory feedback to generate accurate, reliable movements. In many flying insects, strain-sensitive neurons on the wings provide rapid feedback that is critical for stable flight control. While the impacts of wing structure on aerodynamic performance have been widely studied, the impacts of wing structure on sensing are largely unexplored. In this paper, we show how the structural properties of the wing and encoding by mechanosensory neurons interact to jointly determine optimal sensing strategies and performance. Specifically, we examine how neural sensors can be placed effectively on a flapping wing to detect body rotation about different axes, using a computational wing model with varying flexural stiffness. A small set of mechanosensors, conveying strain information at key locations with a single action potential per wingbeat, enable accurate detection of body rotation. Optimal sensor locations are concentrated at either the wing base or the wing tip, and they transition sharply as a function of both wing stiffness and neural threshold. Moreover, the sensing strategy and performance is robust to both external disturbances and sensor loss. Typically, only five sensors are needed to achieve near-peak accuracy, with a single sensor often providing accuracy well above chance. Our results show that small-amplitude, dynamic signals can be extracted efficiently with spatially and temporally sparse sensors in the context of flight. The demonstrated interaction of wing structure and neural encoding properties points to the importance of understanding each in the context of their joint evolution.


Assuntos
Voo Animal/fisiologia , Insetos/anatomia & histologia , Insetos/fisiologia , Modelos Biológicos , Asas de Animais/anatomia & histologia , Asas de Animais/inervação , Potenciais de Ação/fisiologia , Animais , Evolução Biológica , Fenômenos Biomecânicos , Biologia Computacional , Simulação por Computador , Retroalimentação Sensorial/fisiologia , Manduca/anatomia & histologia , Manduca/fisiologia , Mecanorreceptores/fisiologia , Modelos Neurológicos , Rotação , Asas de Animais/fisiologia
15.
Nature ; 535(7611): 252-7, 2016 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-27338790

RESUMO

Immunomodulatory drugs bind to cereblon (CRBN) to confer differentiated substrate specificity on the CRL4(CRBN) E3 ubiquitin ligase. Here we report the identification of a new cereblon modulator, CC-885, with potent anti-tumour activity. The anti-tumour activity of CC-885 is mediated through the cereblon-dependent ubiquitination and degradation of the translation termination factor GSPT1. Patient-derived acute myeloid leukaemia tumour cells exhibit high sensitivity to CC-885, indicating the clinical potential of this mechanism. Crystallographic studies of the CRBN-DDB1-CC-885-GSPT1 complex reveal that GSPT1 binds to cereblon through a surface turn containing a glycine residue at a key position, interacting with both CC-885 and a 'hotspot' on the cereblon surface. Although GSPT1 possesses no obvious structural, sequence or functional homology to previously known cereblon substrates, mutational analysis and modelling indicate that the cereblon substrate Ikaros uses a similar structural feature to bind cereblon, suggesting a common motif for substrate recruitment. These findings define a structural degron underlying cereblon 'neosubstrate' selectivity, and identify an anti-tumour target rendered druggable by cereblon modulation.


Assuntos
Antineoplásicos/farmacologia , Peptídeo Hidrolases/metabolismo , Fatores de Terminação de Peptídeos/metabolismo , Compostos de Fenilureia/farmacologia , Talidomida/análogos & derivados , Proteínas Adaptadoras de Transdução de Sinal , Motivos de Aminoácidos , Antineoplásicos/química , Sítios de Ligação , Cristalografia por Raios X , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Humanos , Fator de Transcrição Ikaros/química , Fator de Transcrição Ikaros/metabolismo , Modelos Moleculares , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Peptídeo Hidrolases/química , Fatores de Terminação de Peptídeos/química , Fatores de Terminação de Peptídeos/deficiência , Compostos de Fenilureia/química , Ligação Proteica , Proteólise/efeitos dos fármacos , Especificidade por Substrato , Talidomida/química , Talidomida/farmacologia , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo
16.
Cogn Emot ; 36(3): 560-567, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34978267

RESUMO

Research on the role of affect in decision-making indicates that both predecisional current and expected affective valence predict choice. However, the exact role of current and expected affect for recurrent decision-making is still a matter of debate. We used a generalised mixed effect model to predict gambling responses in an experience-based learning task from ratings of current and expected affective valence. Results indicate that current and expected affective valence interact to predict choice. While expected valence had the biggest effect size, current valence and the interaction still contributed significantly to the prediction of choice. Resolving the interaction showed that participants relied more on the current valence if expectations were unclear or positive. These findings are discussed in the context of dual-process accounts and the affective signalling hypothesis. In conclusion, current and expected valence depend on one another and interact to predict choice in recurrent decision tasks.


Assuntos
Afeto , Jogo de Azar , Afeto/fisiologia , Humanos
17.
Biophys J ; 120(18): 4079-4090, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34384761

RESUMO

During muscle contraction, myosin motors anchored to thick filaments bind to and slide actin thin filaments. These motors rely on energy derived from ATP, supplied, in part, by diffusion from the sarcoplasm to the interior of the lattice of actin and myosin filaments. The radial spacing of filaments in this lattice may change or remain constant during contraction. If the lattice is isovolumetric, it must expand when the muscle shortens. If, however, the spacing is constant or has a different pattern of axial and radial motion, then the lattice changes volume during contraction, driving fluid motion and assisting in the transport of molecules between the contractile lattice and the surrounding intracellular space. We first create an advective-diffusive-reaction flow model and show that the flow into and out of the sarcomere lattice would be significant in the absence of lattice expansion. Advective transport coupled to diffusion has the potential to substantially enhance metabolite exchange within the crowded sarcomere. Using time-resolved x-ray diffraction of contracting muscle, we next show that the contractile lattice is neither isovolumetric nor constant in spacing. Instead, lattice spacing is time varying, depends on activation, and can manifest as an effective time-varying Poisson ratio. The resulting fluid flow in the sarcomere lattice of synchronous insect flight muscles is even greater than expected for constant lattice spacing conditions. Lattice spacing depends on a variety of factors that produce radial force, including cross-bridges, titin-like molecules, and other structural proteins. Volume change and advective transport varies with the phase of muscle stimulation during periodic contraction but remains significant at all conditions. Although varying in magnitude, advective transport will occur in all cases in which the sarcomere is not isovolumetric. Akin to "breathing," advective-diffusive transport in sarcomeres is sufficient to promote metabolite exchange and may play a role in the regulation of contraction itself.


Assuntos
Miofibrilas , Sarcômeros , Citoesqueleto de Actina , Contração Muscular , Miosinas
18.
Arch Biochem Biophys ; 706: 108923, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34029559

RESUMO

A highly organized and densely packed lattice of molecular machinery within the sarcomeres of muscle cells powers contraction. Although many of the proteins that drive contraction have been studied extensively, the mechanical impact of fluid shearing within the lattice of molecular machinery has received minimal attention. It was recently proposed that fluid flow augments substrate transport in the sarcomere, however, this analysis used analytical models of fluid flow in the molecular machinery that could not capture its full complexity. By building a finite element model of the sarcomere, we estimate the explicit flow field, and contrast it with analytical models. Our results demonstrate that viscous drag forces on sliding filaments are surprisingly small in contrast to the forces generated by single myosin molecular motors. This model also indicates that the energetic cost of fluid flow through viscous shearing with lattice proteins is likely minimal. The model also highlights a steep velocity gradient between sliding filaments and demonstrates that the maximal radial fluid velocity occurs near the tips of the filaments. To our knowledge, this is the first computational analysis of fluid flow within the highly structured sarcomere.


Assuntos
Análise de Elementos Finitos , Modelos Biológicos , Miosinas/fisiologia , Sarcômeros/fisiologia , Animais , Fenômenos Biomecânicos , Simulação por Computador , Humanos , Contração Muscular/fisiologia , Miosinas/ultraestrutura , Reologia , Sarcômeros/ultraestrutura , Termodinâmica , Viscosidade
19.
J Exp Biol ; 224(Pt 4)2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33441388

RESUMO

The interaction between insects and the flowers they pollinate has driven the evolutionary diversity of both insects and flowering plants, two groups with the most numerous species on Earth. Insects use vision and olfaction to localize host plants, but we know relatively little about how they find the tiny nectary opening in the flower, which can be well beyond their visual resolution. Especially when vision is limited, touch becomes crucial in successful insect-plant pollination interactions. Here, we studied the remarkable feeding behavior of crepuscular hawkmoths Manduca sexta, which use their long, actively controlled, proboscis to expertly explore flower-like surfaces. Using machine vision and 3D-printed artificial flower-like feeders, we revealed a novel behavior that shows moths actively probe surfaces, sweeping their proboscis from the feeder edge to its center repeatedly until they locate the nectary opening. Moreover, naive moths rapidly learn to exploit these flowers, and they adopt a tactile search strategy to more directly locate the nectary opening in as few as three to five consecutive visits. Our results highlight the proboscis as a unique active sensory structure and emphasize the central role of touch in nectar foraging insect-plant pollinator interactions.


Assuntos
Manduca , Tato , Animais , Flores , Néctar de Plantas , Plantas , Polinização
20.
PLoS Comput Biol ; 16(1): e1007452, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917816

RESUMO

We develop a method to learn a bio-inspired motion control policy using data collected from hawkmoths navigating in a virtual forest. A Markov Decision Process (MDP) framework is introduced to model the dynamics of moths and sparse logistic regression is used to learn control policy parameters from the data. The results show that moths do not favor detailed obstacle location information in navigation, but rely heavily on optical flow. Using the policy learned from the moth data as a starting point, we propose an actor-critic learning algorithm to refine policy parameters and obtain a policy that can be used by an autonomous aerial vehicle operating in a cluttered environment. Compared with the moths' policy, the policy we obtain integrates both obstacle location and optical flow. We compare the performance of these two policies in terms of their ability to navigate in artificial forest areas. While the optimized policy can adjust its parameters to outperform the moth's policy in each different terrain, the moth's policy exhibits a high level of robustness across terrains.


Assuntos
Simulação por Computador , Modelos Biológicos , Navegação Espacial/fisiologia , Algoritmos , Animais , Biologia Computacional , Tomada de Decisões , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Cadeias de Markov , Mariposas/fisiologia
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