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1.
J Neurosci ; 44(15)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38408872

RESUMO

Why do we move slower as we grow older? The reward circuits of the brain, which tend to invigorate movements, decline with aging, raising the possibility that reduced vigor is due to the diminishing value that our brain assigns to movements. However, as we grow older, it also becomes more effortful to make movements. Is age-related slowing principally a consequence of increased effort costs from the muscles, or reduced valuation of reward by the brain? Here, we first quantified the cost of reaching via metabolic energy expenditure in human participants (male and female), and found that older adults consumed more energy than the young at a given speed. Thus, movements are objectively more costly for older adults. Next, we observed that when reward increased, older adults, like the young, responded by initiating their movements earlier. Yet, unlike the young, they were unwilling to increase their movement speed. Was their reluctance to reach quicker for rewards due to the increased effort costs, or because they ascribed less value to the movement? Motivated by a mathematical model, we next made the young experience a component of aging by making their movements more effortful. Now the young responded to reward by reacting faster but chose not to increase their movement speed. This suggests that slower movements in older adults are partly driven by an adaptive response to an elevated effort landscape. Moving slower may be a rational economic response the brain is making to mitigate the elevated effort costs that accompany aging.


Assuntos
Envelhecimento Saudável , Humanos , Masculino , Feminino , Idoso , Movimento/fisiologia , Recompensa , Hipocinesia , Motivação , Tomada de Decisões/fisiologia
2.
PLoS Comput Biol ; 20(5): e1012169, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38820571

RESUMO

On any given day, we make countless reaching movements to objects around us. While such ubiquity may suggest uniformity, each movement's speed is unique-why is this? Reach speed is known to be influenced by accuracy; we slow down to sustain high accuracy. However, in other forms of movement like walking or running, metabolic cost is often the primary determinant of movement speed. Here we bridge this gap and ask: how do metabolic cost and accuracy interact to determine speed of reaching movements? First, we systematically measure the effect of increasing mass on the metabolic cost of reaching across a range of movement speeds. Next, in a sequence of three experiments, we examine how added mass affects preferred reaching speed across changing accuracy requirements. We find that, while added mass consistently increases metabolic cost thereby leading to slower metabolically optimal movement speeds, self-selected reach speeds are slower than those predicted by an optimization of metabolic cost alone. We then demonstrate how a single model that considers both accuracy and metabolic costs can explain preferred movement speeds. Together, our findings provide a unifying framework to illuminate the combined effects of metabolic cost and accuracy on movement speed and highlight the integral role metabolic cost plays in determining reach speed.


Assuntos
Movimento , Humanos , Movimento/fisiologia , Masculino , Metabolismo Energético/fisiologia , Feminino , Adulto , Modelos Biológicos , Adulto Jovem , Biologia Computacional , Desempenho Psicomotor/fisiologia
3.
J Infect Dis ; 229(Supplement_2): S213-S218, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38019187

RESUMO

The 2022 mpox outbreak primarily involved sexual transmission among men who have sex with men and disproportionately affected persons with human immunodeficiency virus (HIV). We examined viral dynamics and clinical features in a cohort evaluated for mpox infection at a comprehensive HIV clinic in Atlanta, Georgia. Viral DNA was found in 8 oropharyngeal and 5 anorectal specimens among 10 mpox cases confirmed by lesion swab polymerase chain reaction. Within-participant anatomic site of lowest cycle threshold (Ct) value varied, and lower Ct values were found in oropharyngeal and anorectal swabs when corresponding symptoms were present. This provides insight into mpox infection across multiple anatomic sites among people with HIV.


Assuntos
Infecções por HIV , Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Instituições de Assistência Ambulatorial
4.
J Neurosci ; 43(45): 7523-7529, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940591

RESUMO

Rapid progress in our understanding of the brain's learning mechanisms has been accomplished over the past decade, particularly with conceptual advances, including representing behavior as a dynamical system, large-scale neural population recordings, and new methods of analysis of neuronal populations. However, motor and cognitive systems have been traditionally studied with different methods and paradigms. Recently, some common principles, evident in both behavior and neural activity, that underlie these different types of learning have become to emerge. Here we review results from motor and cognitive learning, relying on different techniques and studying different systems to understand the mechanisms of learning. Movement is intertwined with cognitive operations, and its dynamics reflect cognitive variables. Training, in either motor or cognitive tasks, involves recruitment of previously unresponsive neurons and reorganization of neural activity in a low dimensional manifold. Mapping of new variables in neural activity can be very rapid, instantiating flexible learning of new tasks. Communication between areas is just as critical a part of learning as are patterns of activity within an area emerging with learning. Common principles across systems provide a map for future research.


Assuntos
Aprendizagem , Movimento , Aprendizagem/fisiologia , Cognição/fisiologia
5.
J Neurophysiol ; 131(4): 638-651, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38056423

RESUMO

During foraging, animals explore a site and harvest reward and then abandon that site and travel to the next opportunity. One aspect of this behavior involves decision making, and the other involves movement control. These two aspects of behavior may be linked via an underlying desire to maximize a single normative utility: the sum of all rewards acquired, minus all efforts expended, divided by time. According to this theory, the history of rewards, and not just its immediate availability, should dictate how long one should stay and harvest reward and how vigorously one should travel to the next opportunity. We tested this theory in a series of experiments in which humans used their hand to harvest tokens at a reward patch and then used their arm to reach toward another patch. After a history of high rewards, the subjects not only shortened their harvest duration but also moved more vigorously toward the next reward opportunity. In contrast, after a history of high effort they lengthened their harvest duration but reduced their movement vigor, reaching more slowly to the next reward site. Thus, a history of high reward or low effort biased decisions by promoting early abandonment of the reward site and biased movements by promoting vigor.NEW & NOTEWORTHY Much of life is spent foraging. Whereas previous work has focused on the decision regarding time spent harvesting from a reward patch, here we test the idea that both decision making and movement control are tuned to optimize the net rate of reward in an environment. Our results show that movement patterns reflect not just immediate expectations but also past experiences in the environment, providing fundamental insight into the factors governing volitional control of arm movements.


Assuntos
Movimento , Recompensa , Humanos , Tempo de Reação , Mãos , Tomada de Decisões
6.
Environ Geochem Health ; 46(8): 263, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954066

RESUMO

Sustainable management of river systems is a serious concern, requiring vigilant monitoring of water contamination levels that could potentially threaten the ecological community. This study focused on the evaluation of water quality in the Jhelum River (JR), Azad Jammu and Kashmir, and northern Punjab, Pakistan. To achieve this, 60 water samples were collected from various points within the JR Basin (JRB) and subjected to a comprehensive analysis of their physicochemical parameters. The study findings indicated that the concentrations of physicochemical parameters in the JRB water remained within safety thresholds for both drinking and irrigation water, as established by the World Health Organization and Pakistan Environmental Protection Agency. These physicochemical parameters refer to various chemical and physical characteristics of the water that can have implications for both human health (drinking water) and agricultural practices (irrigation water). The spatial variations throughout the river course distinguished between the upstream, midstream, and downstream sections. Specifically, the downstream section exhibited significantly higher values for physicochemical parameters and a broader range, highlighting a substantial decline in its quality. Significant disparities in mean values and ranges were evident, particularly in the case of nitrates and total dissolved solids, when the downstream section was compared with its upstream and midstream counterparts. These variations indicated a deteriorating downstream water quality profile, which is likely attributable to a combination of geological and anthropogenic influences. Despite the observed deterioration in the downstream water quality, this study underscores that the JRB within the upper Indus Basin remains safe and suitable for domestic and agricultural purposes. The JRB was evaluated for various irrigation water quality indices. The principal component analysis conducted in this study revealed distinct covariance patterns among water quality variables, with the first five components explaining approximately 79% of the total variance. Recommending the continued utilization of the JRB for irrigation, we advocate for the preservation and enhancement of water quality in the downstream regions.


Assuntos
Irrigação Agrícola , Água Potável , Monitoramento Ambiental , Rios , Poluentes Químicos da Água , Qualidade da Água , Paquistão , Rios/química , Água Potável/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos
7.
Environ Monit Assess ; 196(4): 365, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483634

RESUMO

Identifying factors contributing to water salinity is paramount in efficiently managing limited water resources in arid environments. The primary objective of this study is to enhance understanding regarding the hydrochemistry, source, and mechanism of water salinity, as well as to assess the suitability of water for various uses in southern Iraq. The groundwater samples were collected from water wells and springs and analyzed for major cations and anions along with stable isotopes (δ18O and δ2H) to accomplish the objective. The analysis of major ion chemistry, hydrochemical techniques, principal component analysis (PCA), and isotope signatures were adopted to determine the primary factors contributing to water mineralization. The study inferred that evaporation and geological processes encompassing water-rock interactions, such as dissolution precipitation and ion exchange, were key processes. The stable isotope analysis revealed that the water originated from meteoric sources and underwent significant evaporation during or before infiltration. The utility assessment of water samples indicates that most samples are not appropriate for consumption and are significantly below the established standards for potable water. In contrast, a significant portion of the groundwater samples were found to meet the criteria for irrigation suitability by adopting Wilcox and the US Salinity Laboratory criteria. The groundwater could be considered for irrigation with proper salinity control management. Overall, this study has significantly improved the understanding of the hydrogeochemical regimes and acts as a first step toward the sustainable utilization of water resources.


Assuntos
Água Potável , Água Subterrânea , Poluentes Químicos da Água , Monitoramento Ambiental/métodos , Salinidade , Iraque , Poluentes Químicos da Água/análise , Água Subterrânea/química , Água Potável/química , Isótopos/análise
8.
J Neurophysiol ; 129(4): 819-832, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36883754

RESUMO

Movement slowness is a common and disruptive symptom of multiple sclerosis (MS). A potential cause is that individuals with MS slow down to conserve energy as a behavioral adjustment to heightened metabolic costs of movement. To investigate this prospect, we measured the metabolic costs of both walking and seated arm reaching at five speeds in persons with mild MS (pwMS; n = 13; 46.0 ± 7.7 yr) and sex- and age-matched controls (HCs; n = 13; 45.8 ± 7.8 yr). Notably, the cohort of pwMS was highly mobile and no individuals required a cane or aid when walking. We found that the net metabolic power of walking was approximately 20% higher for pwMS across all speeds (P = 0.0185). In contrast, we found no differences in the gross power of reaching between pwMS and HCs (P = 0.492). Collectively, our results suggest that abnormal slowness of movement in MS-particularly reaching-is not the consequence of heightened effort costs and that other sensorimotor mechanisms are playing a considerable role in slowing.NEW & NOTEWORTHY Individuals with multiple sclerosis (MS) often move more slowly than those without the disease. A possible cause is that movements in MS are more energetically expensive and slowing is an adaptation to conserve metabolic resources. Here, we find that while walking is more costly for persons with MS, arm-reaching movements are not. These results bring into question the driving force of movement slowness in MS and implicate other motor-related networks contributing to slowing.


Assuntos
Esclerose Múltipla , Humanos , Braço , Caminhada , Movimento , Adaptação Fisiológica
9.
Langmuir ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607611

RESUMO

Water electrolysis has attracted scientists' attention as a green route for energy generation. However, the sluggish kinetics of oxygen evolution reaction (OER) remarkably increases the reaction overpotential. In this work, we developed Co-based nanomaterials as cost-effective, highly efficient catalysts for OER. In this regard, different Co-based metal-organic frameworks (MOFs) were synthesized using different organic linkers. After annealing under inert atmosphere, the corresponding Co-embedded mesoporous carbon (Co/MC) materials were produced. Among them, Co/MC synthesized using 2-methyl imidazole (Co/NMC-2MeIM) expressed the highest surface area (412 m2/g) compared to its counterparts. Furthermore, it expressed a higher degree of defects as depicted by Raman spectra. Co/NMC-2MeIM exhibited the best catalytic performance toward OER in alkaline medium. It afforded an overpotential of 292 mV at a current density of 10 mA cm-2 and a Tafel slope of 99.2 mV dec-1. The superior electrocatalytic performance of Co/NMC-2MeIM is attributed to its high content of Co3+ on the surface, high surface area, and enhanced electrical conductivity induced by nitrogen doping. Furthermore, its high content of pyridinic-N and high degree of defects remarkably enhance the charge transfer between the adsorbed oxygen species and the active sites. These results may pave the avenue toward further investigation of metal/carbon materials in a wide range of electrocatalytic applications.

10.
BMC Med Educ ; 23(1): 426, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291568

RESUMO

BACKGROUND: Ward rounds are a cornerstone in the educational experience of junior doctors and an essential part of teaching patient care. Here, we aimed to assess the doctors' perception of ward rounds as an educational opportunity and to identify the obstacles faced in conducting a proper ward round in Sudanese hospitals. METHOD: A cross-sectional study was conducted from the 15th to the 30th of January 2022 among house officers, medical officers, and registrars in about 50 teaching and referral hospitals in Sudan. House officers and medical officers were considered the learners, while specialist registrars were considered the teachers. Doctors' perceptions were assessed using an online questionnaire, with a 5-level Likert scale to answer questions. RESULTS: A total of 2,011 doctors participated in this study (882 house officers, 697 medical officers, and 432 registrars). The participants were aged 26.9 ± 3.2 years, and females constituted about 60% of the sample. An average of 3.1 ± 6.8 ward rounds were conducted per week in our hospitals, with 11.1 ± 20.3 h spent on ward rounds per week. Most doctors agreed that ward rounds are suitable for teaching patient management (91.3%) and diagnostic investigations (89.1%). Almost all the doctors agreed that being interested in teaching (95.1%) and communicating appropriately with the patients (94.7%) make a good teacher in ward rounds. Furthermore, nearly all the doctors agreed that being interested in learning (94.3%) and communicating appropriately with the teacher (94.5%) make a good student on ward rounds. About 92.8% of the doctors stated that the quality of ward rounds could be improved. The most frequently reported obstacles faced during ward rounds were the noise (70%) and lack of privacy (77%) in the ward environment. CONCLUSION: Ward rounds have a special value in teaching patient diagnosis and management. Being interested in teaching/learning and having good communication skills were the two major criteria that make a good teacher/learner. Unfortunately, ward rounds are faced with obstacles related to the ward environment. It is mandatory to ensure the quality of both ward rounds' teaching and environment to optimize the educational value and subsequently improve patient care practice.


Assuntos
Aprendizagem , Visitas de Preceptoria , Feminino , Humanos , Estudos Transversais , Pessoal de Saúde , Hospitais
11.
Sensors (Basel) ; 24(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38202878

RESUMO

Biometric authentication is a widely used method for verifying individuals' identities using photoplethysmography (PPG) cardiac signals. The PPG signal is a non-invasive optical technique that measures the heart rate, which can vary from person to person. However, these signals can also be changed due to factors like stress, physical activity, illness, or medication. Ensuring the system can accurately identify and authenticate the user despite these variations is a significant challenge. To address these issues, the PPG signals were preprocessed and transformed into a 2-D image that visually represents the time-varying frequency content of multiple PPG signals from the same human using the scalogram technique. Afterward, the features fusion approach is developed by combining features from the hybrid convolution vision transformer (CVT) and convolutional mixer (ConvMixer), known as the CVT-ConvMixer classifier, and employing attention mechanisms for the classification of human identity. This hybrid model has the potential to provide more accurate and reliable authentication results in real-world scenarios. The sensitivity (SE), specificity (SP), F1-score, and area under the receiver operating curve (AUC) metrics are utilized to assess the model's performance in accurately distinguishing genuine individuals. The results of extensive experiments on the three PPG datasets were calculated, and the proposed method achieved ACCs of 95%, SEs of 97%, SPs of 95%, and an AUC of 0.96, which indicate the effectiveness of the CVT-ConvMixer system. These results suggest that the proposed method performs well in accurately classifying or identifying patterns within the PPG signals to perform continuous human authentication.


Assuntos
Identificação Biométrica , Dispositivos Ópticos , Humanos , Fotopletismografia , Benchmarking , Fontes de Energia Elétrica
12.
Sensors (Basel) ; 23(16)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37631741

RESUMO

Cardiovascular disorders are often diagnosed using an electrocardiogram (ECG). It is a painless method that mimics the cyclical contraction and relaxation of the heart's muscles. By monitoring the heart's electrical activity, an ECG can be used to identify irregular heartbeats, heart attacks, cardiac illnesses, or enlarged hearts. Numerous studies and analyses of ECG signals to identify cardiac problems have been conducted during the past few years. Although ECG heartbeat classification methods have been presented in the literature, especially for unbalanced datasets, they have not proven to be successful in recognizing some heartbeat categories with high performance. This study uses a convolutional neural network (CNN) model to combine the benefits of dense and residual blocks. The objective is to leverage the benefits of residual and dense connections to enhance information flow, gradient propagation, and feature reuse, ultimately improving the model's performance. This proposed model consists of a series of residual-dense blocks interleaved with optional pooling layers for downsampling. A linear support vector machine (LSVM) classified heartbeats into five classes. This makes it easier to learn and represent features from ECG signals. We first denoised the gathered ECG data to correct issues such as baseline drift, power line interference, and motion noise. The impacts of the class imbalance are then offset by resampling techniques that denoise ECG signals. An RD-CNN algorithm is then used to categorize the ECG data for the various cardiac illnesses using the retrieved characteristics. On two benchmarked datasets, we conducted extensive simulations and assessed several performance measures. On average, we have achieved an accuracy of 98.5%, a sensitivity of 97.6%, a specificity of 96.8%, and an area under the receiver operating curve (AUC) of 0.99. The effectiveness of our suggested method for detecting heart disease from ECG data was compared with several recently presented algorithms. The results demonstrate that our method is lightweight and practical, qualifying it for continuous monitoring applications in clinical settings for automated ECG interpretation to support cardiologists.


Assuntos
Cardiopatias , Infarto do Miocárdio , Humanos , Coração , Eletrocardiografia , Redes Neurais de Computação , Cardiopatias/diagnóstico
13.
Pharm Dev Technol ; 28(1): 109-123, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36593750

RESUMO

The present study aimed to improve the neuroprotective effect of chrysin (CHR) by combining two formulation techniques, phospholipid (PL) complexation and solid dispersion (SD). CHR-phospholipid complex (CHR-PLC) was prepared through solvent evaporation. The molar ratio CHR/PL (1:3), which exhibited the highest complexation efficiency, was selected for the preparation of CHR-PLC loaded SD (CHR-PLC-SD) with 2-hydroxypropyl ß cyclodextrin (2-HPßCD) and polyvinylpyrrolidone 8000. CHR-PLC/2-HPßCD (1:2, w/w) displayed the highest aqueous solubility of CHR (5.86 times more than that of plain CHR). CHR-SD was also prepared using 2-HPßCD for comparison. The in vitro dissolution of CHR-PLC-SD4 revealed an enhancement in the dissolution rate over CHR-PLC (1:3), CHR-SD, and plain CHR by six times. The optimum formulations and plain CHR were evaluated for their neuroprotective effect on brain aging induced by D-galactose in mice. The results demonstrated a behavioral activity elevation, an increase of AMPK, LKB1, and PGC1α brain contents as well as a reduction of AGEs, GFAP, NT-3, TNF-α, and NF-κß brain contents when compared with those of the D-galactose control group. Thus, the developed formulations stimulated neurogenesis and mitochondrial biogenesis as well as suppressed neuroinflammation and neurodegeneration. The order of activity was as follows: CHR-PLC-SD4 > CHR-PLC (1:3) > CHR-SD > plain CHR.


Assuntos
Fármacos Neuroprotetores , Camundongos , Animais , 2-Hidroxipropil-beta-Ciclodextrina , Fármacos Neuroprotetores/farmacologia , Fosfolipídeos , Galactose , Solubilidade
14.
AAPS PharmSciTech ; 24(2): 58, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36759398

RESUMO

The aim of the current study is the development of a vitamin D3 (VD3)-loaded nanoemulsion (NE) formulation to improve VD3 oral bioavailability for management of vitamin D inadequacy in autistic children. Eight NE formulations were prepared by high-speed homogenization followed by ultrasonication. Four vegetable oils were employed along with two concentrations of Span 20 as the emulsifier. Glycerol, fructose, and mango flavor were included as viscosity modifier, sweetening, and flavoring agents, respectively. The prepared VD3-loaded NE formulations exhibited high drug content (> 98%), droplet size (DS) ranging from 61.15 to 129.8 nm with narrow size distribution, zeta potential values between - 9.83 and - 19.22 mV, and acceptable pH values (4.59-5.89). Storage stability showed that NE formulations underwent coalescence and phase separation during 6 months at room temperature, whereas at refrigerated conditions, formulations showed slight creaming. The optimum formulation (VD3-NE6) revealed a non-significant DS growth at refrigerated conditions and spherical morphology under transmission electron microscopy. VD3-NE6 did not produce any toxic effects to rats treated orally for 3 months, where normal blood picture and kidney and liver functions were observed compared to control rats. Also, serum calcium, oxidative stress, and apoptosis biomarkers remained within normal levels, indicating the safety of the optimum formulation. Furthermore, evaluation of VD3-NE6 oral bioavailability depicted a significant increase in AUC0-72 and Cmax with decreased Tmax compared to plain VD3. The optimum formulation demonstrated improved stability, safety, and oral bioavailability indicating the potential for successful management of vitamin D deficiency in autistic children.


Assuntos
Transtorno Autístico , Nanopartículas , Ratos , Animais , Colecalciferol , Transtorno Autístico/tratamento farmacológico , Emulsões , Sistemas de Liberação de Medicamentos , Vitamina D , Tamanho da Partícula
15.
J Neurophysiol ; 126(4): 1345-1360, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34433001

RESUMO

How does the brain coordinate concurrent adaptation of arm movements and standing posture? From previous studies, the postural control system can use information about previously adapted arm movement dynamics to plan appropriate postural control; however, it is unclear whether postural control can be adapted and controlled independently of arm control. The present study addresses that question. Subjects practiced planar reaching movements while standing and grasping the handle of a robotic arm, which generated a force field to create novel perturbations. Subjects were divided into two groups, for which perturbations were introduced in either an abrupt or a gradual manner. All subjects adapted to the perturbations while reaching with their dominant (right) arm and then switched to reaching with their nondominant (left) arm. Previous studies of seated reaching movements showed that abrupt perturbation introduction led to transfer of learning between arms, but gradual introduction did not. Interestingly, in this study neither group showed evidence of transferring adapted control of arm or posture between arms. These results suggest primarily that adapted postural control cannot be transferred independently of arm control in this task paradigm. In other words, whole body postural movement planning related to a concurrent arm task is dependent on information about arm dynamics. Finally, we found that subjects were able to adapt to the gradual perturbation while experiencing very small errors, suggesting that both error size and consistency play a role in driving motor adaptation.NEW & NOTEWORTHY This study examined adaptation of arm and postural control to novel dynamics while standing and reaching and subsequent transfer between reaching arms. Neither arm nor postural control was transferred between arms, suggesting that postural planning is highly dependent on the concurrent arm movement.


Assuntos
Adaptação Fisiológica/fisiologia , Braço/fisiologia , Atividade Motora/fisiologia , Equilíbrio Postural/fisiologia , Posição Ortostática , Transferência de Experiência/fisiologia , Adulto , Humanos , Adulto Jovem
16.
BMC Immunol ; 22(1): 37, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134627

RESUMO

OBJECTIVES: Chronic inflammatory diseases, including diabetes and cardiovascular disease, are heterogeneous and often co-morbid, with increasing global prevalence. Uncontrolled type 2 diabetes (T2D) can result in severe inflammatory complications. As neutrophils are essential to normal and aberrant inflammation, we conducted RNA-seq transcriptomic analyses to investigate the association between neutrophil gene expression and T2D phenotype. As specialized pro-resolving lipid mediators (SPM) act to resolve inflammation, we further surveyed the impact of neutrophil receptor binding SPM resolvin E1 (RvE1) on isolated diabetic and healthy neutrophils. METHODS: Cell isolation and RNA-seq analysis of neutrophils from N = 11 T2D and N = 7 healthy individuals with available clinical data was conducted. Additionally, cultured neutrophils (N = 3 T2D, N = 3 healthy) were perturbed with increasing RvE1 doses (0 nM, 1 nM, 10 nM, or 100 nM) prior to RNA-seq. Data was evaluated through a bioinformatics pipeline including pathway analysis and post hoc false discovery rate (FDR)-correction. RESULTS: We observed significant differential expression of 50 genes between T2D and healthy neutrophils (p < 0.05), including decreased T2D gene expression in inflammatory- and lipid-related genes SLC9A4, NECTIN2, and PLPP3 (p < 0.003). RvE1 treatment induced dose-dependent differential gene expression (uncorrected p < 0.05) across groups, including 59 healthy and 216 T2D neutrophil genes. Comparing T2D to healthy neutrophils, 1097 genes were differentially expressed across RvE1 doses, including two significant genes, LILRB5 and AKR1C1, involved in inflammation (p < 0.05). CONCLUSIONS: The neutrophil transcriptomic database revealed novel chronic inflammatory- and lipid-related genes that were differentially expressed between T2D cells when compared to controls, and cells responded to RvE1 dose-dependently by gene expression changes. Unraveling the mechanisms regulating abnormalities in diabetic neutrophil responses could lead to better diagnostics and therapeutics targeting inflammation and inflammation resolution.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Inflamação/genética , Neutrófilos/fisiologia , 20-Hidroxiesteroide Desidrogenases/genética , Adulto , Idoso , Antígenos CD/genética , Células Cultivadas , Diabetes Mellitus Tipo 2/genética , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/genética , Masculino , Pessoa de Meia-Idade , Nectinas/genética , Fosfatidato Fosfatase/genética , Análise de Sequência de RNA , Trocadores de Sódio-Hidrogênio/genética , Transcriptoma
17.
Proc Natl Acad Sci U S A ; 115(44): E10476-E10485, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30322938

RESUMO

During foraging, animals decide how long to stay at a patch and harvest reward, and then, they move with certain vigor to another location. How does the brain decide when to leave, and how does it determine the speed of the ensuing movement? Here, we considered the possibility that both the decision-making and the motor control problems aimed to maximize a single normative utility: the sum of all rewards acquired minus all efforts expended divided by total time. This optimization could be achieved if the brain compared a local measure of utility with its history. To test the theory, we examined behavior of people as they gazed at images: they chose how long to look at the image (harvesting information) and then moved their eyes to another image, controlling saccade speed. We varied reward via image content and effort via image eccentricity, and then, we measured how these changes affected decision making (gaze duration) and motor control (saccade speed). After a history of low rewards, people increased gaze duration and decreased saccade speed. In anticipation of future effort, they lowered saccade speed and increased gaze duration. After a history of high effort, they elevated their saccade speed and increased gaze duration. Therefore, the theory presented a principled way with which the brain may control two aspects of behavior: movement speed and harvest duration. Our experiments confirmed many (but not all) of the predictions, suggesting that harvest duration and movement speed, fundamental aspects of behavior during foraging, may be governed by a shared principle of control.


Assuntos
Tomada de Decisões , Tempo de Reação , Movimentos Sacádicos , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
18.
Proc Natl Acad Sci U S A ; 115(27): 7105-7110, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29915086

RESUMO

Experimental evolution is a critical tool in many disciplines, including metabolic engineering and synthetic biology. However, current methods rely on the chance occurrence of a key step that can dramatically accelerate evolution in natural systems, namely increased gene dosage. Our studies sought to induce the targeted amplification of chromosomal segments to facilitate rapid evolution. Since increased gene dosage confers novel phenotypes and genetic redundancy, we developed a method, Evolution by Amplification and Synthetic Biology (EASy), to create tandem arrays of chromosomal regions. In Acinetobacter baylyi, EASy was demonstrated on an important bioenergy problem, the catabolism of lignin-derived aromatic compounds. The initial focus on guaiacol (2-methoxyphenol), a common lignin degradation product, led to the discovery of Amycolatopsis genes (gcoAB) encoding a cytochrome P450 enzyme that converts guaiacol to catechol. However, chromosomal integration of gcoAB in Pseudomonas putida or A. baylyi did not enable guaiacol to be used as the sole carbon source despite catechol being a growth substrate. In ∼1,000 generations, EASy yielded alleles that in single chromosomal copy confer growth on guaiacol. Different variants emerged, including fusions between GcoA and CatA (catechol 1,2-dioxygenase). This study illustrates the power of harnessing chromosomal gene amplification to accelerate the evolution of desirable traits.


Assuntos
Proteínas de Bactérias/genética , Cromossomos Bacterianos/genética , Evolução Molecular , Dosagem de Genes , Genes Bacterianos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/enzimologia
19.
Behav Brain Sci ; 44: e138, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34588089

RESUMO

In science, as in life, one can only hope to both inform others, and be informed by them. The commentaries associated with our book Vigor have highlighted the many ways in which the theory that we proposed can be improved. For example, there are a myriad of factors that need to be considered in a fully encompassing objective function. The neural mechanisms underlying the links between movement and decision-making have yet to be unraveled. The implications of a two-way interaction between movement and decisions at both the individual and social levels remain to be understood. The commentaries outline future questions, and encouragingly highlight the diversity of science communities that may be linked via the concept of vigor.


Assuntos
Movimento , Retroalimentação , Humanos
20.
Toxicol Mech Methods ; 31(6): 467-475, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34027802

RESUMO

The major sources for human exposure to Benzo [a] pyrene (B[a]P) are contaminated food, water, and inhalation of polycyclic aromatic hydrocarbon. B[a]P is a well-known human genotoxic carcinogen (IARC Group 1). It has a tumorigenic potential in virtually all in vivo experimental animal model systems. The study aimed to evaluate the effect of catechin hydrate (CH) against B [a] P-induced toxicity in the lung of adult albino rats. Thirty-six adult male albino rats (150-200 g) were divided into six groups, three control groups, and three experimental groups: B[a] P-treated group, (CH)-treated group, and B[a] P+(CH)-treated group. At the end of the fourth week of the study, blood samples and lung tissues were obtained for the biochemical and genotoxicity, RT-PCR, histopathological, and immunohistochemical investigations, respectively. Our results clarified that B[a] P exposure caused a subsequent decrease in the activities of antioxidant enzymes (SOD, CAT), and conversely (MDA) levels elevated markedly. Also, B[a] P induced DNA damages and activated the apoptotic pathway, presented by upregulated Bax, caspase-3, and downregulated Bcl-2 gens. However, treatment with CH increased antioxidant enzymes as well as regulated apoptosis. Discernible histological changes in the lung also supported the protective effects of CH. These findings suggested that CH is an effective natural product that attenuates Benzo [a] pyrene-induced lung toxicity.


Assuntos
Pneumopatias/induzido quimicamente , Animais , Apoptose , Benzo(a)pireno/toxicidade , Catequina , Dano ao DNA , Pulmão , Masculino , Estresse Oxidativo , Ratos
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