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1.
Nature ; 632(8026): 768-774, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39169245

RESUMO

Artificial neural networks, deep-learning methods and the backpropagation algorithm1 form the foundation of modern machine learning and artificial intelligence. These methods are almost always used in two phases, one in which the weights of the network are updated and one in which the weights are held constant while the network is used or evaluated. This contrasts with natural learning and many applications, which require continual learning. It has been unclear whether or not deep learning methods work in continual learning settings. Here we show that they do not-that standard deep-learning methods gradually lose plasticity in continual-learning settings until they learn no better than a shallow network. We show such loss of plasticity using the classic ImageNet dataset and reinforcement-learning problems across a wide range of variations in the network and the learning algorithm. Plasticity is maintained indefinitely only by algorithms that continually inject diversity into the network, such as our continual backpropagation algorithm, a variation of backpropagation in which a small fraction of less-used units are continually and randomly reinitialized. Our results indicate that methods based on gradient descent are not enough-that sustained deep learning requires a random, non-gradient component to maintain variability and plasticity.

2.
Nature ; 609(7925): 58-64, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36045237

RESUMO

Polymer membranes are widely used in separation processes including desalination1, organic solvent nanofiltration2,3 and crude oil fractionation4,5. Nevertheless, direct evidence of subnanometre pores and a feasible method of manipulating their size is still challenging because of the molecular fluctuations of poorly defined voids in polymers6. Macrocycles with intrinsic cavities could potentially tackle this challenge. However, unfunctionalized macrocycles with indistinguishable reactivities tend towards disordered packing in films hundreds of nanometres thick7-9, hindering cavity interconnection and formation of through-pores. Here, we synthesized selectively functionalized macrocycles with differentiated reactivities that preferentially aligned to create well-defined pores across an ultrathin nanofilm. The ordered structure was enhanced by reducing the nanofilm thickness down to several nanometres. This orientated architecture enabled direct visualization of subnanometre macrocycle pores in the nanofilm surfaces, with the size tailored to ångström precision by varying the macrocycle identity. Aligned macrocycle membranes provided twice the methanol permeance and higher selectivity compared to disordered counterparts. Used in high-value separations, exemplified here by enriching cannabidiol oil, they achieved one order of magnitude faster ethanol transport and threefold higher enrichment than commercial state-of-the-art membranes. This approach offers a feasible strategy for creating subnanometre channels in polymer membranes, and demonstrates their potential for accurate molecular separations.

3.
Mol Cell Neurosci ; 126: 103863, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37268282

RESUMO

Glucose accesses the brain primarily via the astrocyte cell compartment, where it passes through the glycogen shunt before catabolism to the oxidizable fuel L-lactate. Glycogen phosphorylase (GP) isoenzymes GPbb and GPmm impose distinctive control of ventromedial hypothalamic nucleus (VMN) glucose-regulatory neurotransmission during hypoglycemia, but lactate and/or gliotransmitter involvement in those actions is unknown. Lactate or the octadecaneuropeptide receptor antagonist cyclo(1-8)[DLeu5] OP (LV-1075) did not affect gene product down-regulation caused by GPbb or GPmm siRNA, but suppressed non-targeted GP variant expression in a VMN region-specific manner. Hypoglycemic up-regulation of neuronal nitric oxide synthase was enhanced in rostral and caudal VMN by GPbb knockdown, yet attenuated by GPMM siRNA in the middle VMN; lactate or LV-1075 reversed these silencing effects. Hypoglycemic inhibition of glutamate decarboxylase65/67 was magnified by GPbb (middle and caudal VMN) or GPmm (middle VMN) knockdown, responses that were negated by lactate or LV-1075. GPbb or GPmm siRNA enlarged hypoglycemic VMN glycogen profiles in rostral and middle VMN. Lactate and LV-1075 elicited progressive rostral VMN glycogen augmentation in GPbb knockdown rats, but stepwise-diminution of rostral and middle VMN glycogen after GPmm silencing. GPbb, not GPmm, knockdown caused lactate or LV-1075 - reversible amplification of hypoglycemic hyperglucagonemia and hypercorticosteronemia. Results show that lactate and octadecaneuropeptide exert opposing control of GPbb protein in distinct VMN regions, while the latter stimulates GPmm. During hypoglycemia, GPbb and GPmm may respectively diminish (rostral, caudal VMN) or enhance (middle VMN) nitrergic transmission and each oppose GABAergic signaling (middle VMN) by lactate- and octadecaneuropeptide-dependent mechanisms.


Assuntos
Hipoglicemia , Núcleo Hipotalâmico Ventromedial , Ratos , Animais , Núcleo Hipotalâmico Ventromedial/metabolismo , Isoenzimas/metabolismo , Ratos Sprague-Dawley , Hipoglicemia/metabolismo , Glucose/metabolismo , Glicogênio/metabolismo , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Neurotransmissores/farmacologia , Glicogênio Fosforilase/metabolismo , Glicogênio Fosforilase/farmacologia , Lactatos/metabolismo , Lactatos/farmacologia , Hormônios/metabolismo , Hormônios/farmacologia
4.
Health Educ Res ; 38(4): 338-349, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-36880171

RESUMO

Waterpipe tobacco smoking is a public health concern that poses many of the same health risks as cigarette smoking, especially among young adults-a subpopulation characterized by the highest prevalence of waterpipe tobacco smoking. Nevertheless, it remains understudied relative to other forms of tobacco use. We examined sociodemographic, behavioral and cognitive factors associated with young adults' motivation to quit waterpipe smoking using a theory-informed approach. We completed a secondary analysis of baseline data on waterpipe tobacco smoking beliefs and behavior collected from 349 US young adults aged 18-30 years. We analyzed sociodemographics, tobacco use and cessation behaviors and perceptions, and theory-related constructs associated with motivation to quit waterpipe tobacco smoking using linear regression. Overall, participants reported low motivation (mean = 2.68, SD = 1.56, scale range 1-7) and high self-efficacy (mean = 5.12, SD = 1.79) to quit waterpipe tobacco smoking. In multivariable analysis, prior quit attempts (ß = 1.10, P < 0.01), greater perceived risks of waterpipe tobacco smoking (ß = 0.42, P < 0.01) and increasingly negative attitudes toward waterpipe tobacco smoking (ß = 0.29, P < 0.01) were associated with higher motivation to quit. These findings highlight the importance of those factors as potential cessation determinants. These findings can help guide the development and refinement of interventions targeting young adult waterpipe tobacco smoking.


Assuntos
Fumar Cigarros , Abandono do Hábito de Fumar , Tabaco para Cachimbos de Água , Humanos , Adulto Jovem , Abandono do Hábito de Fumar/psicologia , Motivação , Comportamentos Relacionados com a Saúde
5.
Int J Behav Med ; 30(2): 268-278, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35543861

RESUMO

BACKGROUND: Adherence to COVID-19 protective measures is lowest for young people and males. The current study investigated characteristics associated with adherence to COVID-19 protective measures among male youth during the early months of the pandemic. METHOD: The study used data from a prospective cohort study among male youth with baseline assessment in 2015/2016 and follow-up measurements in 2019 and summer 2020. Attrition-weighted multivariable ordinal logistic and log-binomial regression models were used to assess factors associated with adherence to overall and specific adherence measures, respectively. RESULTS: Among 571 male youth (mean age 18.5), overall adherence was higher for those who were older (OR: 1.15; 95% CI: 1.03-1.30), non-White (OR: 1.96; 95% CI: 1.20-3.32), and residing in an urban area (OR: 2.06; 95% CI: 1.46-3.01). Overall adherence was lower for those who had a history of being drunk (OR: 0.65; 95% CI: 0.42-0.99). For outdoor mask-wearing, adherence was higher for youth with attention-deficit disorder or attention-deficit/hyperactivity disorder (RR: 1.58; 95% CI: 1.16-1.97) and lower for youth who currently used tobacco products (RR: 0.42; 95% CI: 0.21-0.70). Before a statewide mask mandate was issued, non-White youth were more likely to report wearing masks in outdoor spaces than their non-Hispanic White peers (RR: 2.34; 95% CI: 1.75-3.23). CONCLUSION: The study identified demographic, psychosocial, and behavioral factors associated with adherence to COVID-19 protective behaviors among male youth. The findings illustrate characteristics that could be leveraged for targeted preventive efforts during the ongoing pandemic and future outbreaks in a low-compliance group.


Assuntos
COVID-19 , Masculino , Humanos , Adolescente , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Estudos Prospectivos , Surtos de Doenças , Pandemias/prevenção & controle
6.
Sensors (Basel) ; 23(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37050601

RESUMO

Several researchers have proposed secure authentication techniques for addressing privacy and security concerns in the fifth-generation (5G)-enabled vehicle networks. To verify vehicles, however, these conditional privacy-preserving authentication (CPPA) systems required a roadside unit, an expensive component of vehicular networks. Moreover, these CPPA systems incur exceptionally high communication and processing costs. This study proposes a CPPA method based on fog computing (FC), as a solution for these issues in 5G-enabled vehicle networks. In our proposed FC-CPPA method, a fog server is used to establish a set of public anonymity identities and their corresponding signature keys, which are then preloaded into each authentic vehicle. We guarantee the security of the proposed FC-CPPA method in the context of a random oracle. Our solutions are not only compliant with confidentiality and security standards, but also resistant to a variety of threats. The communication costs of the proposal are only 84 bytes, while the computation costs are 0.0031, 2.0185 to sign and verify messages. Comparing our strategy to similar ones reveals that it saves time and money on communication and computing during the performance evaluation phase.

7.
Georgian Med News ; (344): 72-76, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38236102

RESUMO

Tension impacts wound healing and scarring. Tissue stress reduces blood flow and promotes fibroblastic response in wound treatment. Botox injections reduce tension. A total of 18 male albino rats weighing 250-350 grams each got 1 IU of Botox and saline injected into a subcutaneous muscle in the center of each 1.5 CM two circles with 4.5 CM a gap between them. Group A seven days pre-operatively; group B, after wound incidence. The study compared Botox-treated wounds to those treated immediately after surgery. Group A animals were surgery-ready after 7 days, removed full-thickness skin. Group B got Botox and saline in separate cages following full-thickness skin excision. Each group had three equal subgroups. Each group had immunohistochemistry tests on days 3, 7, and 14. and histological test on day 14 only, Skin biopsies following euthanasia showed significant variations between A and B groups. On day three, the group A showed increase significantly MMP-9 expression than B group. On day 7, the group A displayed a significant increase CD31 expression, suggesting significant new blood vessel development than group B. On day 14, both groups showed strong MMP-9 and CD31 expression, demonstrated greater endothelial cell, and keratinocyte proliferation resulted in very well re-epithelialization. Botox injection before surgery improved wound healing and reduced fibrosis and scarring.


Assuntos
Toxinas Botulínicas Tipo A , Cicatriz , Masculino , Ratos , Animais , Cicatriz/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , Metaloproteinase 9 da Matriz , Cicatrização , Pele
8.
Georgian Med News ; (338): 63-68, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37419473

RESUMO

The Aloe vera plant is a cactus-like plant in the Liliacea family that has been known and utilized for its medical benefits. It has been attempted to be used as a remineralizing agent and shows an antibacterial effect. Aim of the study - assessment of the remineralizing effect of solution of saturated Aloe vera gel compared to distal water by microhardness Vickers test and Densometric X-Ray Analysis and effect of Aloe vera gel against Enterococcus faecalis. 10 extracted permanent molars were used in this in vitro study. each tooth enrolls in Teflon tape and only the enamel of the occlusal surface was exposed to a demineralizing solution (acid etch) for 45 seconds in-vitro and randomly assigned to two groups: Group 1 was treated with distal water; group 2 was treated with Aloe vera gel. All groups except the control baseline group were treated with their respective remineralizing solution for 10 days. Vicker's Microhardness Number (VHN) and Densometric X-Ray Analysis were carried out at baseline, post-demineralization and later post 10 days of remineralization. The antibacterial effect of Aloe vera gel was assessed by the disc diffusion method. The filter paper was immersed in 20µl of different concentrations of Aloe vera gel extract as fresh Aloe vera (100 %) and (50 % and 25 %) diluted with de-ionized water after that the disc was distributed in a plate containing the E. faecalis. Antibiotics disc of Augmentin (Amoxicillin and Clavulanic acid 30ug) were also poured in the same plate and incubated at 37°C for 24 hours and the zone of inhibition of antibiotic was measured for comparison with a zone of inhibition of filter paper saturated with Aloe vera gel. Densitometric X-Ray Analysis and Microhardness Number (VHN) evaluation showed improvement in the enamel density and the surface hardness after remineralization. The mean value in the group treated with Aloe vera solution was higher than the recorded mean value for the group treated with distal water. There was a significant difference between Aloe vera solution and distal water. Significant (p-value≤0.05) after 10 days. The antibacterial effect showed that E. faecalis was resistant to Aloe vera gel in different concentrations compared with Augmentin (Amoxicillin and Clavulanic acid 30ug). Aloe vera gel could be used for caries prevention in terms of safety and efficiency. While E. faecalis show resistance activity against Aloe vera gel.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio , Enterococcus faecalis , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Amoxicilina/farmacologia
9.
J Appl Microbiol ; 132(5): 3461-3475, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34995396

RESUMO

The biodesulfurization activity of bacteria through the 4S pathway in aqueous-oil emulsions is affected by various operational factors. These factors also demonstrate interacting effects that influence the potential for field applications of biodesulfurization technology and can solely be deciphered through multi-variable experiments. In this study, the effects of the influential factors and their interactions on the desulfurizing activity of a newly identified desulfurizing bacterium, Rhodococcus sp, FUM94 were quantitatively investigated. The capacity improvement achieved through optimized values obtained in this study is significant due to its simple implementation to large scale processes. This is the most simple and the most cost-effective way to scale-up a biodesulfurization process.Using response surface methodology (RSM). Optimum values of the factors were identified with the objective of maximizing biodesulfurization activity. Results revealed that the desulfurization activity of the biocatalyst increased from 0.323 ± 0.072 to 46.57 ± 4.556 mmol 2-Hydroxybiphenyl (kg dry cell weight)-1 h-1 at the optimized conditions of 6 h reaction time, 2 g.L-1 biocatalyst concentration, 0.54 mM (100 ppm) dibenzothiophene (DBT) concentration (sulfur source), and 25% oil phase fraction. Desirability analysis proved that the selected conditions are the most desirable combination of factors (desirability value = 0.896) to achieve the highest biodesulfurization activity of the biocatalyst. A comparison between the biodesulfurization capacity achieved in this study and the capacities reported in similar studies published in the past two decades revealed that biodesulfurization under optimized operational conditions outperforms previously proposed techniques.


Assuntos
Rhodococcus , Biodegradação Ambiental , Emulsões , Rhodococcus/metabolismo , Enxofre/metabolismo , Água/metabolismo
10.
Sensors (Basel) ; 22(5)2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35270843

RESUMO

Existing identity-based schemes utilized in Vehicular Ad hoc Networks (VANETs) rely on roadside units to offer conditional privacy-preservation authentication and are vulnerable to insider attacks. Achieving rapid message signing and verification for authentication is challenging due to complex operations, such as bilinear pairs. This paper proposes a secure pseudonym-based conditional privacy-persevering authentication scheme for communication security in VANETs. The Elliptic Curve Cryptography (ECC) and secure hash cryptographic function were used in the proposed scheme for signing and verifying messages. After a vehicle receives a significant amount of pseudo-IDs and the corresponding signature key from the Trusted Authority (TA), it uses them to sign a message during the broadcasting process. Thus, the proposed scheme requires each vehicle to check all the broadcasting messages received. Besides, in the proposed scheme, the TA can revoke misbehaving vehicles from continuously broadcasting signed messages, thus preventing insider attacks. The security analysis proved that the proposed scheme fulfilled the security requirements, including identity privacy-preservation, message integrity and authenticity, unlinkability, and traceability. The proposed scheme also withstood common security attacks such as man-in-the-middle, impersonation, modification, and replay attacks. Besides, our scheme was resistant against an adaptive chosen-message attack under the random oracle model. Furthermore, our scheme did not employ bilinear pairing operations; therefore, the performance analysis and comparison showed a lower resulting overhead than other identity-based schemes. The computation costs of the message signing, individual signature authentication, and batch signature authentication were reduced by 49%, 33.3%, and 90.2%, respectively.


Assuntos
Anônimos e Pseudônimos , Privacidade , Comunicação , Segurança Computacional , Humanos
11.
Sensors (Basel) ; 22(13)2022 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-35808521

RESUMO

The security and privacy concerns in vehicular communication are often faced with schemes depending on either elliptic curve (EC) or bilinear pair (BP) cryptographies. However, the operations used by BP and EC are time-consuming and more complicated. None of the previous studies fittingly tackled the efficient performance of signing messages and verifying signatures. Therefore, a chaotic map-based conditional privacy-preserving authentication (CM-CPPA) scheme is proposed to provide communication security in 5G-enabled vehicular networks in this paper. The proposed CM-CPPA scheme employs a Chebyshev polynomial mapping operation and a hash function based on a chaotic map to sign and verify messages. Furthermore, by using the AVISPA simulator for security analysis, the results of the proposed CM-CPPA scheme are good and safe against general attacks. Since EC and BP operations do not employ the proposed CM-CPPA scheme, their performance evaluation in terms of overhead such as computation and communication outperforms other most recent related schemes. Ultimately, the proposed CM-CPPA scheme decreases the overhead of computation of verifying the signatures and signing the messages by 24.2% and 62.52%, respectively. Whilst, the proposed CM-CPPA scheme decreases the overhead of communication of the format tuple by 57.69%.


Assuntos
Segurança Computacional , Privacidade , Algoritmos , Comunicação , Confidencialidade
12.
Hemoglobin ; 46(1): 7-9, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35950585

RESUMO

Bangladesh is a country with a population of 160 million with a gross national income per capita of US$1580.00. The major health problems in Bangladesh include acute respiratory infection, pneumonia, dengue fever, malaria and water-borne diseases. The health care system in Bangladesh is divided into primary secondary and tertiary levels, with each level having their own breakdown of available hospital beds and other treatment facilities. Thalassemia is a major health problem in Bangladesh. There are two types of thalassemia in Bangladesh: ß-thalassemia (ß-thal) and Hb E (HBB: c.79G>A)/ß-thal, with the prevalence rate of ß-thal trait being 4.1% and Hb E trait 6.1%. This study discusses spectrum types of thalassemia and hemoglobinopathies in Bangladesh and the types of carrier detection. The distribution of common mutations of thalassemia are also discussed and the distribution frequencies of genotypes and alleles of ß-thal and Hb E patients are also compared. Additionally, we also conducted a study of the spectrum of thalassemia using high performance liquid chromatography (HPLC) of the tribal populations and analyzed the findings in our discussion. The results of these studies show that the phenotypic and genotypic presentation in Bangladesh is highly diverse. To properly understand this, we have to conduct an epidemiological survey of the population. Furthermore, there also has to be improvement on the awareness of thalassemia among the population to properly equip themselves to survive this disease.


Assuntos
Hemoglobinopatias , Talassemia alfa , Talassemia beta , Ásia , Bangladesh/epidemiologia , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/genética , Humanos , Mutação , Talassemia alfa/genética , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Talassemia beta/genética
13.
Molecules ; 27(9)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35565960

RESUMO

A new xanthone glycoside, 1,3,5,6-tetrahydroxyxanthone-C-4-ß-d-glucopyranoside was isolated from the methanol extract of Mangifera indica leaves (Anacardiaceae) growing in Egypt. The structure was clarified by 1D and 2D-NMR spectroscopic data. The physicochemical properties of the compound such as lipophilicity, solubility, and formulation considerations were predicted via in silico ADMET technique using the SwissADME server. This technique provided Lipinski's rule of five, such as GIT absorption, distribution, metabolism, and skin permeation. The in vitro inhibitory activities against aging-mediated enzymes such as collagenase, elastase, hyaluronidase, and tyrosinase were assessed. The compound exhibited remarkable anti-collagenase, anti-elastase, anti-hyaluronidase, and anti-tyrosinase effects with IC50 values of 1.06, 419.10, 1.65, and 0.48 µg/mL, respectively, compared to the positive control. The compound showed promising predicted aqueous solubility and reasonable skin penetration suggesting the suitability of the compound for topical formulation as an anti-aging agent for cosmetic preparations.


Assuntos
Glicosídeos Cardíacos , Mangifera , Envelhecimento da Pele , Xantonas , Colagenases/metabolismo , Glicosídeos/farmacologia , Hialuronoglucosaminidase/metabolismo , Mangifera/metabolismo , Monofenol Mono-Oxigenase , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Xantonas/química , Xantonas/farmacologia
14.
Sensors (Basel) ; 21(24)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34960311

RESUMO

Communications between nodes in Vehicular Ad-Hoc Networks (VANETs) are inherently vulnerable to security attacks, which may mean disruption to the system. Therefore, the security and privacy issues in VANETs are entitled to be the most important. To address these issues, the existing Conditional Privacy-Preserving Authentication (CPPA) schemes based on either public key infrastructure, group signature, or identity have been proposed. However, an attacker could impersonate an authenticated node in these schemes for broadcasting fake messages. Besides, none of these schemes have satisfactorily addressed the performance efficiency related to signing and verifying safety traffic-related messages. For resisting impersonation attacks and achieving better performance efficiency, a Secure and Efficient Conditional Privacy-Preserving Authentication (SE-CPPA) scheme is proposed in this paper. The proposed SE-CPPA scheme is based on the cryptographic hash function and bilinear pair cryptography for the signing and verifying of messages. Through security analysis and comparison, the proposed SE-CPPA scheme can accomplish security goals in terms of formal and informal analysis. More precisely, to resist impersonation attacks, the true identity of the vehicle stored in the tamper-proof device (TPD) is frequently updated, having a short period of validity. Since the MapToPoint hash function and a large number of cryptography operations are not employed, simulation results show that the proposed SE-CPPA scheme outperforms the existing schemes in terms of computation and communication costs. Finally, the proposed SE-CPPA scheme reduces the computation costs of signing the message and verifying the message by 99.95% and 35.93%, respectively. Meanwhile, the proposed SE-CPPA scheme reduces the communication costs of the message size by 27.3%.

15.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33451134

RESUMO

The catecholamine norepinephrine (NE) links hindbrain metabolic-sensory neurons with key glucostatic control structures in the brain, including the ventromedial hypothalamic nucleus (VMN). In the brain, the glycogen reserve is maintained within the astrocyte cell compartment as an alternative energy source to blood-derived glucose. VMN astrocytes are direct targets for metabolic stimulus-driven noradrenergic signaling due to their adrenergic receptor expression (AR). The current review discusses recent affirmative evidence that neuro-metabolic stability in the VMN may be shaped by NE influence on astrocyte glycogen metabolism and glycogen-derived substrate fuel supply. Noradrenergic modulation of estrogen receptor (ER) control of VMN glycogen phosphorylase (GP) isoform expression supports the interaction of catecholamine and estradiol signals in shaping the physiological stimulus-specific control of astrocyte glycogen mobilization. Sex-dimorphic NE control of glycogen synthase and GP brain versus muscle type proteins may be due, in part, to the dissimilar noradrenergic governance of astrocyte AR and ER variant profiles in males versus females. Forthcoming advances in the understanding of the molecular mechanistic framework for catecholamine stimulus integration with other regulatory inputs to VMN astrocytes will undoubtedly reveal useful new molecular targets in each sex for glycogen mediated defense of neuronal metabolic equilibrium during neuro-glucopenia.


Assuntos
Astrócitos/metabolismo , Metabolismo dos Carboidratos/efeitos dos fármacos , Glicogênio/metabolismo , Norepinefrina/metabolismo , Núcleo Hipotalâmico Ventromedial/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Regulação da Expressão Gênica , Glucose/metabolismo , Humanos , Neurônios/metabolismo , Norepinefrina/farmacologia , Receptores Adrenérgicos/genética , Receptores Adrenérgicos/metabolismo , Rombencéfalo/efeitos dos fármacos , Rombencéfalo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Núcleo Hipotalâmico Ventromedial/efeitos dos fármacos
16.
J Theor Biol ; 496: 110278, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32298689

RESUMO

MOTIVATION: Interactions between proteins and peptides influence biological functions. Predicting such bio-molecular interactions can lead to faster disease prevention and help in drug discovery. Experimental methods for determining protein-peptide binding sites are costly and time-consuming. Therefore, computational methods have become prevalent. However, existing models show extremely low detection rates of actual peptide binding sites in proteins. To address this problem, we employed a two-stage technique - first, we extracted the relevant features from protein sequences and transformed them into images applying a novel method and then, we applied a convolutional neural network to identify the peptide binding sites in proteins. RESULTS: We found that our approach achieves 67% sensitivity or recall (true positive rate) surpassing existing methods by over 35%.


Assuntos
Redes Neurais de Computação , Proteínas , Sítios de Ligação , Peptídeos/metabolismo , Ligação Proteica
17.
Mol Cell Neurosci ; 95: 51-58, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30660767

RESUMO

The ventromedial hypothalamic nucleus (VMN) is a critical component of the neural circuitry that regulates glucostasis. Astrocyte glycogen is a vital reserve of glucose and its oxidizable metabolite L-lactate. In hypoglycemic female rats, estradiol-dependent augmentation of VMN glycogen phosphorylase (GP) protein requires hindbrain catecholamine input. Research here investigated the premise that norepinephrine (NE) regulation of VMN astrocyte metabolism shapes local glucoregulatory neurotransmitter signaling in this sex. Estradiol-implanted ovariectomized rats were pretreated by intra-VMN administration of the monocarboxylate transporter inhibitor alpha-cyano-4-hydroxy-cinnamic acid (4CIN) or vehicle before NE delivery to that site. NE caused 4CIN-reversible reduction or augmentation of VMN glycogen synthase and phosphorylase expression. 4CIN prevented NE stimulation of gluco-inhibitory (glutamate decarboxylase65/67) and suppression of gluco-stimulatory (neuronal nitric oxide synthase) neuron marker proteins. These outcomes imply that effects of noradrenergic stimulation of VMN astrocyte glycogen depletion on glucoregulatory transmitter signaling may be mediated, in part, by glycogen-derived substrate fuel provision. NE control of astrocyte glycogen metabolism may involve down-regulated adrenoreceptor (AR), e.g. alpha1 and alpha2, alongside amplified beta1 AR and estrogen receptor-beta signaling. Noradrenergic hypoglycemia was refractory to 4CIN, implying that additional NE-sensitive VMN glucoregulatory neurochemicals may be insensitive to monocarboxylate uptake. Augmentation of circulating free fatty acids by combinatory NE and 4CIN, but not NE alone implies that acute hypoglycemia induced here is an insufficient stimulus for mobilization of these fuels, but is adequate when paired with diminished brain monocarboxylate fuel availability.


Assuntos
Glucose/metabolismo , Glicogênio/metabolismo , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Norepinefrina/farmacologia , Núcleo Hipotalâmico Ventromedial/metabolismo , Animais , Astrócitos/metabolismo , Ácidos Cumáricos/farmacologia , Inibidores Enzimáticos/farmacologia , Receptor beta de Estrogênio/metabolismo , Estrogênios/deficiência , Ácidos Graxos/metabolismo , Feminino , Glicogênio Sintase/antagonistas & inibidores , Transportadores de Ácidos Monocarboxílicos/metabolismo , Norepinefrina/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos/metabolismo , Núcleo Hipotalâmico Ventromedial/citologia
18.
An Acad Bras Cienc ; 92(2): e20191107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520220

RESUMO

Eimeriosis is caused by a protozoan parasite of the genus Eimeria and infection affecting most domestic animal species. The aim of this research was to comprehend the impact of selenium nanoparticles (SeNPs) on eimeriosis induced by Eimeria papillata in mouse jejunum, and how they work as antioxidants and anti-apoptotic agents against eimeriosis. The numbers of meronts, gamonts, and developing oocysts of E. papillata reduced after the infected mice were treated with the SeNPs. The levels of malondialdehyde (MDA), nitric oxide (NO), and other oxidative stress-related molecules, such as glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), were assayed. E. papillata was able to change the redox status of the jejunal cells; this was confirmed by the elevation of the MDA and NO levels, and the decrease of the GSH levels and the activities of the antioxidant enzymes CAT and SOD. SeNP treatment significantly reversed this disturbance of the redox status. The expression levels of the apoptotic markers Bax and caspase-3 in the jejunal samples were evaluated using qRT-PCR. The SeNPs decreased the Bax and caspase-3 expression after being administered to the E. papillata-infected mice. Collectively, the SeNPs demonstrated antioxidant and anti-apoptotic activities against murine eimeriosis.


Assuntos
Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Coccidiose/tratamento farmacológico , Nanopartículas/administração & dosagem , Selênio/administração & dosagem , Animais , Coccidiose/parasitologia , Coccidiose/patologia , Modelos Animais de Doenças , Camundongos
19.
Int J Mol Sci ; 21(6)2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32188013

RESUMO

The mediobasal hypothalamus (MBH) shapes the neural regulation of glucostasis by 5'-AMP-activated protein kinase (AMPK)-dependent mechanisms. Yet, the neurochemical identity and neuroanatomical distribution of MBH neurons that express glucoprivic-sensitive AMPK remain unclear. The neurotransmitters γ-aminobutyric acid (GABA) and nitric oxide (NO) act within the MBH to correspondingly inhibit or stimulate glucose counter-regulation. The current review highlights recent findings that GABA and NO, neurons located in the ventromedial hypothalamic nucleus (VMN), a distinct important element of the MBH, are direct targets of noradrenergic regulatory signaling, and thereby, likely operate under the control of hindbrain metabolic-sensory neurons. The ovarian hormone estradiol acts within the VMN to govern energy homeostasis. Discussed here is current evidence that estradiol regulates GABA and NO nerve cell receptivity to norepinephrine and moreover, controls the noradrenergic regulation of AMPK activity in each cell type. Future gains in insight on mechanisms underpinning estradiol's impact on neurotransmitter communication between the hindbrain and hypothalamic AMPKergic neurons are expected to disclose viable new molecular targets for the therapeutic simulation of hormonal enhancement of neuro-metabolic stability during circumstances of diminished endogenous estrogen secretion or glucose dysregulation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Estradiol/farmacologia , Norepinefrina/metabolismo , Células Receptoras Sensoriais/metabolismo , Núcleo Hipotalâmico Ventromedial/metabolismo , Animais , Glicemia/metabolismo , Feminino , Glucose/metabolismo , Glutamato Descarboxilase , Glicogênio/metabolismo , Homeostase , Hipotálamo , Óxido Nítrico , Óxido Nítrico Sintase , Receptores de Estrogênio , Rombencéfalo , Transativadores , Ácido gama-Aminobutírico
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