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Infertility is a heterogeneous phenotype, and for many couples, the causes of fertility problems remain unknown. One understudied hypothesis is that allelic interactions between the genotypes of the two parents may influence the risk of infertility. Our aim was, therefore, to investigate how allelic interactions can be modeled using parental genotype data linked to 15,789 pregnancies selected from the Norwegian Mother, Father, and Child Cohort Study. The newborns in 1304 of these pregnancies were conceived using assisted reproductive technologies (ART), and the remainder were conceived naturally. Treating the use of ART as a proxy for infertility, different parameterizations were implemented in a genome-wide screen for interaction effects between maternal and paternal alleles at the same locus. Some of the models were more similar in the way they were parameterized, and some produced similar results when implemented on a genome-wide scale. The results showed near-significant interaction effects in genes relevant to the phenotype under study, such as Dynein axonemal heavy chain 17 (DNAH17) with a recognized role in male infertility. More generally, the interaction models presented here are readily adaptable to the study of other phenotypes in which maternal and paternal allelic interactions are likely to be involved.
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Encapsulation of transition metals represents a crucial method for modifying the electronic structure and regulating the reactivity of fullerene, thereby expanding its applications. Herein, we present calculations with density functional theory methods to investigate the mechanisms of the Diels-Alder (DA) reactions of cyclopentadiene and La@C60 or Gd@C60 as well as their tricationic derivatives. Our findings indicate that the encapsulation of La and Gd into the C60 cage is thermodynamically favorable. The DA reactions are favored by the presence of La and Gd, with lower barriers, though the regioselectivity, favoring 6-6 bonds in the fullerene, is not affected. The effect of external electric fields has been also considered.
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BACKGROUND: China has the third largest number of TB cases in the world, and the average annual floating population in China is more than 200 million, the increasing floating population across regions has a tremendous potential for spreading infectious diseases, however, the role of increasing massive floating population in tuberculosis transmission is yet unclear in China. METHODS: 29,667 tuberculosis flow data were derived from the new smear-positive pulmonary tuberculosis cases in China. Spatial variation of TB transmission was measured by geodetector q-statistic and spatial interaction model was used to model the tuberculosis flow and the regional socioeconomic factors. RESULTS: Tuberculosis transmission flow presented spatial heterogeneity. The Pearl River Delta in southern China and the Yangtze River Delta along China's east coast presented as the largest destination and concentration areas of tuberculosis inflows. Socioeconomic factors were determinants of tuberculosis flow. Some impact factors showed different spatial associations with tuberculosis transmission flow. A 10% increase in per capita GDP was associated with 10.2% in 2010 or 2.1% in 2012 decrease in tuberculosis outflows from the provinces of origin, and 1.2% in 2010 or 0.5% increase in tuberculosis inflows to the destinations and 18.9% increase in intraprovincial flow in 2012. Per capita net income of rural households and per capita disposable income of urban households were positively associated with tuberculosis flows. A 10% increase in per capita net income corresponded to 14.0% in 2010 or 3.6% in 2012 increase in outflows from the origin, 44.2% in 2010 or 12.8% increase in inflows to the destinations and 47.9% increase in intraprovincial flows in 2012. Tuberculosis incidence had positive impacts on tuberculosis flows. A 10% increase in the number of tuberculosis cases corresponded to 2.2% in 2010 or 1.1% in 2012 increase in tuberculosis inflows to the destinations, 5.2% in 2010 or 2.0% in 2012 increase in outflows from the origins, 11.5% in 2010 or 2.2% in 2012 increase in intraprovincial flows. CONCLUSIONS: Tuberculosis flows had clear spatial stratified heterogeneity and spatial autocorrelation, regional socio-economic characteristics had diverse and statistically significant effects on tuberculosis flows in the origin and destination, and income factor played an important role among the determinants.
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Factores Socioeconómicos , Humanos , China/epidemiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/transmisión , Tuberculosis/epidemiología , Tuberculosis/transmisión , Femenino , Masculino , Población Rural/estadística & datos numéricosRESUMEN
Poor self-esteem relates closely to youth maladjustment and appears to be predicted by peer victimization experiences. However, not all peer victimized adolescents face the same risk for self-esteem erosion over time. Drawing upon the Bi-Dimensional Framework for resilience and extant research, the present study examined the potential moderating role of cognitive reappraisal in the prospective relationship from peer victimization to self-esteem. To increase precision of findings the long-term impact of self-esteem on peer victimization was also tested. Self-reported data were collected from 285 early adolescents (Mage = 10.53 years, SD = 0.16; 54.0% girls) at two waves, spaced 1-year. Latent moderated structural equation analysis showed that peer victimization was negatively related to later self-esteem, but only for youth displaying low levels of cognitive reappraisal. For adolescents with high levels of cognitive reappraising, peer victimization was not found to predict any changes in self-esteem over time. The long-term impact of self-esteem on peer victimization was not supported. Overall the present study suggests that enhancing cognitive reappraisal could be a promising avenue for lowering risk for poor self-esteem in young individuals experiencing peer victimization.
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BACKGROUND: Cancer, a complex and deadly health concern today, is characterized by forming potentially malignant tumors or cancer cells. The dynamic interaction between these cells and their environment is crucial to the disease. Mathematical models can enhance our understanding of these interactions, helping us predict disease progression and treatment strategies. METHODS: In this study, we develop a fractional tumor-immune interaction model specifically for lung cancer (FTIIM-LC). We present some definitions and significant results related to the Caputo operator. We employ the generalized Laguerre polynomials (GLPs) method to find the optimal solution for the FTIIM-LC model. We then conduct a numerical simulation and compare the results of our method with other techniques and real-world data. RESULTS: We propose a FTIIM-LC model in this paper. The approximate solution for the proposed model is derived using a series of expansions in a new set of polynomials, the GLPs. To streamline the process, we integrate Lagrange multipliers, GLPs, and operational matrices of fractional and ordinary derivatives. We conduct a numerical simulation to study the effects of varying fractional orders and achieve the expected theoretical results. CONCLUSION: The findings of this study demonstrate that the optimization methods used can effectively predict and analyze complex phenomena. This innovative approach can also be applied to other nonlinear differential equations, such as the fractional Klein-Gordon equation, fractional diffusion-wave equation, breast cancer model, and fractional optimal control problems.
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Neoplasias Pulmonares , Humanos , Simulación por Computador , Progresión de la Enfermedad , Modelos TeóricosRESUMEN
BACKGROUND: Early life in-utero can have long-term influence on the mental health status of individuals in adulthood, such as depression. Age, gender, socio-economic status, education, and geography are demographic factors shown to be particularly vulnerable towards the development of depressive symptoms. In addition, climate risks on depression include sunlight, rain, and temperature. However, whether climate factors in early life have a long-term influence on depression related to demographic vulnerability remains unknown. Here, the present study explored the association between birth seasonality and adulthood depressive symptoms. METHODS: We employed data from the project of Chinese Labour-forces Dynamic Survey (CLDS) 2016, containing the epidemiological data of depressive symptoms with a probability proportional to size cluster and random cluster sampling method in 29 provinces of China. A final sample size of 16,185 participants was included. Birth seasonality included spring (March, April, and May), summer (June, July, and August), autumn (September, October, and November), and winter (December, January, and February). RESULTS: We found that born in Autumn peaked lowest rate of having depressive symptoms (16.8%) and born in Summer (vs. Autumn) had a significant higher ratio (OR = 1.14, 95%CI = 1.02, 1.29) when controlling for demographic variables. In addition, demographic odds ratio of having depressive symptoms differed between people born in different seasons, particular for age and geography. CONCLUSION: Our findings suggest that birth seasonality influences the sensitive link of depressive symptoms with age and geography. It implicates early life climate environment may play a role in the development of adulthood depressive symptoms.
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Depresión , Salud Mental , Adulto , Humanos , Embarazo , Femenino , Depresión/epidemiología , Clima , Estaciones del Año , PartoRESUMEN
We tested the validity of two alternative accounts of the Attentional Boost Effect (ABE) - the finding that words associated with to-be-responded targets are recognized better than words associated with to-be-ignored distractors. The distinctiveness hypothesis assumes that, during recognition, participants probe their memories for distinctive information confirming that a word was studied (e.g., "I remember having pressed the spacebar, so I must have studied the word"). This strategy cannot be used in a between-subjects condition in which participants cannot appreciate the differences between target - and distractor-paired words. In agreement, Experiments 1A and 1B found that the ABE was significant in a within-subjects design, whereas it was eliminated in a between-subjects design. On the other hand, the performance anticipation hypothesis assumes that, during the study phase, participants anticipate the need of responding to a subset of target-paired words: this would create a persistent performance anticipation that would prevent them from effectively encoding distractor-paired words. In contrast with this account, we found that, when blocks of five distractor trials were regularly alternated with blocks of five target trials in Experiment 2, recognition accuracy decreased linearly in both conditions. Overall, these results suggest that distinctiveness, but not performance anticipation, might underlie the ABE.
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Atención , Memoria , Humanos , Reconocimiento en Psicología , Recuerdo MentalRESUMEN
The maximum temperature limit at which liquid boils explosively is referred to as the superheat limit of liquid. Through various experimental studies on the superheating limit of liquids, rapid evaporation of liquids has been observed at the superheating limit. This study explored the water nucleation process at the superheat limit achieved in micro-platinum wires using a molecular interaction model. According to the molecular interaction model, the nucleation rate and time delay at 576.2 K are approximately 2.1 × 1011/(µm3µs) and 5.7 ns, respectively. With an evaporation rate (116.0 m/s) much faster than that of hydrocarbons (14.0 m/s), these readings show that explosive boiling or rapid phase transition from liquid to vapor can occur at the superheat limit of water. Subsequent bubble growth after bubble nucleation was also considered.
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This study deals with the problem of the population shrinking in habitats affected by aging and excessive migration outflows. First, a control-oriented population dynamics model was proposed that catches the effect of depopulation. The model also includes the effect of spatial interaction-driven migration flows on population size. The resulting model is a non-homogeneous ordinary differential equation. It includes such phenomena that are important from the control point of view, such as the influence of migration costs on population dynamics, the impact of aging on population size, or the effect of the habitats' carrying capacity on migration flows. Based on the model, controllability conditions are formulated and a control strategy was developed that is meant to avoid the depopulation of the habitat. The control method acts on the migration costs to achieve the control goal and requires only population size measurements. Simulation measurements are presented in the paper to show the effectiveness of the proposed modeling and control methods.
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Conservación de los Recursos Naturales , Ecosistema , Dinámica Poblacional , Densidad de Población , Simulación por ComputadorRESUMEN
The vertebrate vestibular system is crucial for balance and navigation, and the evolution of its form and function in relation to species' lifestyle and mode of locomotion has been the focus of considerable recent study. Most research, however, has concentrated on aboveground mammals, with much less published on subterranean fauna. Here, we explored variation in anatomy and sensitivity of the semicircular canals among 91 mammal species, including both subterranean and non-subterranean representatives. Quantitative phylogenetically informed analyses showed significant widening of the canals relative to radius of curvature in subterranean species. A relative canal width above 0.166 indicates with 95% certainty that a species is subterranean. Fluid-structure interaction modelling predicted that canal widening leads to a substantial increase in canal sensitivity; a reasonably good estimation of the absolute sensitivity is possible based on the absolute internal canal width alone. In addition, phylogenetic comparative modelling and functional landscape exploration revealed repeated independent evolution of increased relative canal width and anterior canal sensitivity associated with the transition to a subterranean lifestyle, providing evidence of parallel adaptation. Our results suggest that living in dark, subterranean tunnels requires good balance and/or navigation skills which may be facilitated by more sensitive semicircular canals.
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Mamíferos , Canales Semicirculares , Animales , Filogenia , Canales Semicirculares/anatomía & histología , Canales Semicirculares/fisiología , Mamíferos/anatomía & histología , Mamíferos/fisiología , Locomoción , Adaptación FisiológicaRESUMEN
Following the April 2018 reemergence of Ebola in a rural region of the Democratic Republic of the Congo (DRC), the virus spread to an urban center by early May. Within 2 wk of the first case confirmation, a vaccination campaign was initiated in which 3,017 doses were administered to contacts of cases and frontline healthcare workers. To evaluate the spatial dynamics of Ebola transmission and quantify the impact of vaccination, we developed a geographically explicit model that incorporates high-resolution data on poverty and population density. We found that while Ebola risk was concentrated around sites initially reporting infections, longer-range dissemination also posed a risk to areas with high population density and poverty. We estimate that the vaccination program contracted the geographical area at risk for Ebola by up to 70.4% and reduced the level of risk within that region by up to 70.1%. The early implementation of vaccination was critical. A delay of even 1 wk would have reduced these effects to 33.3 and 44.8%, respectively. These results underscore the importance of the rapid deployment of Ebola vaccines during emerging outbreaks to containing transmission and preventing global spread. The spatiotemporal framework developed here provides a tool for identifying high-risk regions, in which surveillance can be intensified and preemptive control can be implemented during future outbreaks.
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Vacunas contra el Virus del Ébola , Fiebre Hemorrágica Ebola/prevención & control , Vacunación/estadística & datos numéricos , República Democrática del Congo , Humanos , Factores de TiempoRESUMEN
The relationship between trauma exposure and posttraumatic stress symptoms (PTSS) is well-documented, but less is known about factors that contribute to the expression of PTSS following community violence exposure, particularly among emerging adults of color. Utilizing the Person-Environment Interaction model (Slaug et al., 2018), this study examined the role of relational factors, specifically ethnic identity, community cohesion, and social support, associated with PTSS following exposure to community violence. Participants included 243 emerging adult university students of color (Mage = 20.27, SD = 1.95, 83.5% female). Linear regression analyses indicated that less frequent trauma exposure and greater perceived social support were related to lower PTSS. A significant interaction was also found between social support and exposure to community violence, such that at low levels of social support, individuals with more community violence exposure had the highest levels of PTSS. Regression and moderation analyses indicated that ethnic identity and community cohesion were not significantly associated with PTSS in this sample. Findings highlight the importance of incorporating social support strategies in treatments for PTSS following community violence exposure.
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Exposición a la Violencia , Trastornos por Estrés Postraumático , Adulto , Etnicidad , Femenino , Humanos , Masculino , Apoyo Social , Trastornos por Estrés Postraumático/diagnóstico , Violencia , Adulto JovenRESUMEN
Obtaining the total wavefunction evolution of interacting quantum systems provides access to important properties, such as entanglement, shedding light on fundamental aspects, e.g., quantum energetics and thermodynamics, and guiding towards possible application in the fields of quantum computation and communication. We consider a two-level atom (qubit) coupled to the continuum of travelling modes of a field confined in a one-dimensional chiral waveguide. Originally, we treated the light-matter ensemble as a closed, isolated system. We solve its dynamics using a collision model where individual temporal modes of the field locally interact with the qubit in a sequential fashion. This approach allows us to obtain the total wavefunction of the qubit-field system, at any time, when the field starts in a coherent or a single-photon state. Our method is general and can be applied to other initial field states.
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In this study, the bioprotective potential of Lactobacillus sakei CTC494 against Listeria monocytogenes CTC1034 was evaluated on vacuum packaged hot-smoked sea bream at 5 °C and dynamic temperatures ranging from 3 to 12 °C. The capacity of three microbial competition interaction models to describe the inhibitory effect of L. sakei CTC494 on L. monocytogenes was assessed based on the Jameson effect and Lotka-Volterra approaches. A sensory analysis was performed to evaluate the spoiling capacity of L. sakei CTC494 on the smoked fish product at 5 °C. Based on the sensory results, the bioprotection strategy against the pathogen was established by inoculating the product at a 1:2 ratio (pathogen:bioprotector, log CFU/g). The kinetic growth parameters of both microorganisms were estimated in mono-culture at constant storage (5 °C). In addition, the inhibition function parameters of the tested interaction models were estimated in co-culture at constant and dynamic temperature storage using as input the mono-culture kinetic parameters. The growth potential (δ log) of L. monocytogenes, in mono-culture, was 3.5 log on smoked sea bream during the experimental period (20 days). In co-culture, L. sakei CTC494 significantly reduced the capability of L. monocytogenes to grow, although its effectiveness was temperature dependent. The LAB strain limited the growth of the pathogen under storage at 5 °C (<1 log increase) and at dynamic profile 2 (<2 log increase). Besides, under storage at dynamic profile 1, the growth of L. monocytogenes was inhibited (<0.5 log increase). These results confirmed the efficacy of L. sakei CTC494 for controlling the pathogen growth on the studied fish product. The Lotka-Volterra competition model showed slightly better fit to the observed L. monocytogenes growth response than the Jameson-based models according to the statistical performance. The proposed modelling approach could support the assessment and establishment of bioprotective culture-based strategies aimed at reducing the risk of listeriosis linked to the consumption of RTE hot-smoked sea bream.
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Productos Pesqueros/microbiología , Conservación de Alimentos/métodos , Latilactobacillus sakei/fisiología , Listeria monocytogenes/crecimiento & desarrollo , Animales , Antibiosis , Embalaje de Alimentos , Listeria monocytogenes/fisiología , Dorada/microbiologíaRESUMEN
AIMS: Secondary prevention of coronary heart disease is of utmost importance to facilitate people to achieve health outcomes and behaviours. This study was to investigate the effect of a nursing intervention based on Cox's interaction model of client health behaviour to improve health outcomes and behaviours of secondary prevention of coronary heart disease. DESIGN: This study is a cluster randomised controlled trial. METHODS: Participants were recruited between August and November 2019 in two community settings in Hengyang city, Hunan province, China. Participants in the intervention group received a nursing intervention based on Cox's interaction model of client health behaviour and routine health education, while those in the control group received routine health education only. The outcome variables included self-management, physical activity, medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, blood pressure, body mass index (BMI), and low-density lipoprotein cholesterol (LDL-C). The influential statistical tests applied to analyse the data included χ2 tests and t tests. RESULTS: Seventy-seven participants completed this study. Compared with the control group (n = 40), the intervention group (n = 37) showed statistically significant better health outcomes and behaviours regarding self-management, physical activity (except for high energy consumption), medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, systolic blood pressure, BMI, and LDL-C. However, there was no statistically significant difference in diastolic blood pressure and high energy consumption for physical activity. CONCLUSION: A well-developed nursing intervention based on Cox's interaction model of client health behaviour could successfully improve health outcomes and behaviours of secondary prevention of coronary heart disease. Such an intervention may be incorporated into community healthcare practice by nurses to improve patient care. IMPACT: This study provides a valuable insight to facilitate further development of effective nursing interventions to improve secondary prevention of coronary heart disease in community settings.
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Enfermedad Coronaria , Conductas Relacionadas con la Salud , Presión Sanguínea , Enfermedad Coronaria/prevención & control , Ejercicio Físico , Humanos , Prevención SecundariaRESUMEN
For Huntington disease, identification of brain regions related to motor impairment can be useful for developing interventions to alleviate the motor symptom, the major symptom of the disease. However, the effects from the brain regions to motor impairment may vary for different groups of patients. Hence, our interest is not only to identify the brain regions but also to understand how their effects on motor impairment differ by patient groups. This can be cast as a model selection problem for a varying-coefficient regression. However, this is challenging when there is a pre-specified group structure among variables. We propose a novel variable selection method for a varying-coefficient regression with such structured variables and provide a publicly available R package svreg for implementation of our method. Our method is empirically shown to select relevant variables consistently. Also, our method screens irrelevant variables better than existing methods. Hence, our method leads to a model with higher sensitivity, lower false discovery rate and higher prediction accuracy than the existing methods. Finally, we found that the effects from the brain regions to motor impairment differ by disease severity of the patients. To the best of our knowledge, our study is the first to identify such interaction effects between the disease severity and brain regions, which indicates the need for customized intervention by disease severity.
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Enfermedad de Huntington , Trastornos Motores , Atrofia/patología , Encéfalo/diagnóstico por imagen , Humanos , Enfermedad de Huntington/patología , Imagen por Resonancia Magnética , Trastornos Motores/patologíaRESUMEN
Studies of the Madden-Julian Oscillation (MJO) have progressed considerably during the past decades in observations, numerical modeling, and theoretical understanding. Many theoretical attempts have been made to identify the most essential processes responsible for the existence of the MJO. Criteria are proposed to separate a hypothesis from a theory (based on the first principles with quantitative and testable assumptions, able to predict quantitatively the fundamental scales and eastward propagation of the MJO). Four MJO theories are selected to be summarized and compared in this article: the skeleton theory, moisture-mode theory, gravity-wave theory, and trio-interaction theory of the MJO. These four MJO theories are distinct from each other in their key assumptions, parameterized processes, and, particularly, selection mechanisms for the zonal spatial scale, time scale, and eastward propagation of the MJO. The comparison of the four theories and more recent development in MJO dynamical approaches lead to a realization that theoretical thinking of the MJO is diverse and understanding of MJO dynamics needs to be further advanced.
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A four-dimensional model was built to mimic the cross-talk among plasma glucose, plasma insulin, intracellular glucose and cytoplasmic calcium of a cardiomyocyte. A time delay was considered to represent the time required for performing various cellular mechanisms between activation of insulin receptor and subsequent glucose entry from extracellular region into intracellular region of a cardiac cell. We analysed the delay-induced model and deciphered conditions for stability and bifurcation. Extensive numerical computations were performed to validate the analytical results and give further insights. Sensitivity study of the system parameters using LHS-PRCC method reveals that some rate parameters, which represent the input of plasma glucose, absorption of glucose by noncardiac cells and insulin production, are sensitive and may cause significant change in the system dynamics. It was observed that the time taken for transportation of extracellular glucose into the cell through GLUT4 plays an important role in maintaining physiological oscillations of the state variables. Parameter recalibration exercise showed that reduced input rate of glucose in the blood plasma or an alteration in transportation delay may be used for therapeutic targets in diabetic-like condition for maintaining normal cardiac function.
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Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Espacio Extracelular/metabolismo , Glucosa/metabolismo , Modelos Biológicos , Miocitos Cardíacos/patología , Transporte Biológico , Glucemia/metabolismo , Diabetes Mellitus/sangre , Transportador de Glucosa de Tipo 4/metabolismo , CinéticaRESUMEN
Parasitic plants have a unique heterotrophic lifestyle based on the extraction of water and nutrients from host plants. Some parasitic plant species, particularly those of the family Orobanchaceae, attack crops and cause substantial yield losses. The breeding of resistant crop varieties is an inexpensive way to control parasitic weeds, but often does not provide a long-lasting solution because the parasites rapidly evolve to overcome resistance. Understanding mechanisms underlying naturally occurring parasitic plant resistance is of great interest and could help to develop methods to control parasitic plants. In this review, we describe the virulence mechanisms of parasitic plants and resistance mechanisms in their hosts, focusing on obligate root parasites of the genera Orobanche and Striga. We noticed that the resistance (R) genes in the host genome often encode proteins with nucleotide-binding and leucine-rich repeat domains (NLR proteins), hence we proposed a mechanism by which host plants use NLR proteins to activate downstream resistance gene expression. We speculated how parasitic plants and their hosts co-evolved and discussed what drives the evolution of virulence effectors in parasitic plants by considering concepts from similar studies of plant-microbe interaction. Most previous studies have focused on the host rather than the parasite, so we also provided an updated summary of genomic resources for parasitic plants and parasitic genes for further research to test our hypotheses. Finally, we discussed new approaches such as CRISPR/Cas9-mediated genome editing and RNAi silencing that can provide deeper insight into the intriguing life cycle of parasitic plants and could potentially contribute to the development of novel strategies for controlling parasitic weeds, thereby enhancing crop productivity and food security globally.
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Interacciones Huésped-Parásitos/fisiología , Orobanche/parasitología , Striga/fisiología , Evolución Biológica , Orobanche/genética , Striga/genética , Transcriptoma/genética , Virulencia/genéticaRESUMEN
The present study provides new evidence that cationic porphyrins may be considered as tunable platforms to interfere with the structural "key code" present on the 20S proteasome α-rings and, by consequence, with its catalytic activity. Here, we describe the functional and conformational effects on the 20S proteasome induced by the cooperative binding of the tri-cationic 5-(phenyl)-10,15,20-(tri N-methyl-4-pyridyl) porphyrin (Tris-T4). Our integrated kinetic, NMR, and in silico analysis allowed us to disclose a complex effect on the 20S catalytic activity depending on substrate/porphyrin concentration. The analysis of the kinetic data shows that Tris-T4 shifts the relative populations of the multiple interconverting 20S proteasome conformations leading to an increase in substrate hydrolysis by an allosteric pathway. Based on our Tris-T4/h20S interaction model, Tris-T4 is able to affect gating dynamics and substrate hydrolysis by binding to an array of negatively charged and hydrophobic residues present on the protein surface involved in the 20S molecular activation by the regulatory proteins (RPs). Accordingly, despite the fact that Tris-T4 also binds to the α3ΔN mutant, allosteric modulation is not observed since the molecular mechanism connecting gate dynamics with substrate hydrolysis is impaired. We envisage that the dynamic view of the 20S conformational equilibria, activated through cooperative Tris-T4 binding, may work as a simplified model for a better understanding of the intricate network of 20S conformational/functional states that may be mobilized by exogenous ligands, paving the way for the development of a new generation of proteasome allosteric modulators.