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Unraveling CRP/cAMP-mediated metabolic regulation in Escherichia coli persister cells.

A substantial gap persists in our comprehension of how bacterial metabolism undergoes rewiring during the transition to a persistent state. Also, it remains unclear which metabolic mechanisms become indispensable for persister cell survival. To address these questions, we directed our efforts towards persister cells in Escherichia coli that emerge during the late stationary phase. These cells have been recognized for their exceptional resilience and are commonly believed to be in a dormant state. Our results indicate that the global metabolic regulator Crp/cAMP redirects the metabolism of these antibiotic-tolerant cells from anabolism to oxidative phosphorylation. Although our data demonstrates that persisters exhibit a reduced metabolic rate compared to rapidly growing exponential-phase cells, their survival still relies on energy metabolism. Extensive genomic-level analyses of metabolomics, proteomics, and single-gene deletions consistently highlight the critical role of energy metabolism, specifically the tricarboxylic acid (TCA) cycle, electron transport chain (ETC), and ATP synthase, in sustaining persister levels within cell populations. Altogether, this study provides much-needed clarification regarding the role of energy metabolism in antibiotic tolerance and highlights the importance of using a multipronged approach at the genomic level to obtain a broader picture of the metabolic state of persister cells.

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Effect of transcranial direct current stimulation over the primary motor cortex on short-term balance acquisition in healthy individuals

BackgroundThe primary motor cortex (M1) is central to motor learning processes, and an increasing number of studies have suggested its role in balance control. However, the specific role of M1 in balance control remains unclear, and a causal contribution to improvements in balance ability after balance training has not yet been proven. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modifies brain activity and enables to probe the involvement of M1 in balance learning. The current study aims to explore the role of M1 in the acquisition of balance skills by applying tDCS during short-term perturbation-based balance training.MethodsThirty-four participants were randomly assigned to one of three groups receiving balance training combined with tDCS: anodal tDCS, sham tDCS, and a control group without stimulation. All participants were involved in a structured, three-session perturbation-based balance training program completed within one week. During these sessions, the assigned tDCS protocol was applied over the M1 leg area concurrently with the training sessions. We analyzed electroencephalography (EEG) and balance ability during balance perturbations and changes in cortico-spinal excitability at rest. Balance perturbations were applied by translating the standing surface forward and backward. An acoustic signal was given two seconds before perturbation in an additional condition to reveal the effect of perturbation anticipation on reactive cortical responses.ResultsThe results indicate that balance ability, measured by center of mass (COM) displacement and joint excursions, was improved in forward perturbation across all groups, with the anodal stimulation group showing the largest improvement relative to baseline performance following training. Moreover, the anodal stimulation group showed a significant decrease in alpha band power following forward perturbations compared to baseline values after training. N1 latency was reduced across all participants in both perturbation directions after training. However, only the anodal stimulation group showed a significant reduction in backward perturbations compared to baseline values. While training did not induce any significant change in short-interval intracortical inhibition (SICI) measured by Transcranial Magnetic Stimulation (TMS), it increased intracortical facilitation (ICF) in the right tibialis anterior (TA) muscle across all groups, independent of the stimulation condition.ConclusionsThis study provides evidence that tDCS over the M1 area facilitates balance skill acquisition, possibly by facilitating motor preparation and execution and improving the efficiency of sensorimotor integration processes, as shown by decreased alpha power and N1 latency. These findings may have implications for the potential use of tDCS in improving balance control.

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Dimensions of participation as predictors of satisfaction with roles and abilities after traumatic brain injury.

This study aimed to determine the relationship of participation dimensions with satisfaction with social roles and activities after traumatic brain injury (TBI). Secondary analysis of baseline data from 127 participants enrolled in the MoodTracker intervention trial (https://ClinicalTrials.gov Identifier NCT04410770). Participants (Mage = 35.24) were predominately male (64.6%) and non-Hispanic White (70.1%). Primary measures were the TBI Quality of Life scales for Satisfaction With Ability to Participate in Social Roles and Activities, Ability to Participate in Social Roles and Activities, Independence, Stigma, and Self-Esteem and the Participation Assessment With Recombined Tools-Objective Out and About, Social Relations, and Productivity subscales. We performed a hierarchical regression to determine the unique association of different participation dimensions to Satisfaction with Social Roles and Activities. The Participation Assessment With Recombined Tools-Objective scores, representing the frequency of participation in activities, explained 18% of the variance (R² change = .177, p < .001) in Satisfaction with Social Roles and Activities. Ability to Participate in Social Roles and Activities and Independence, representing a person's perceived participation ability, explained 40% of the variance (R² change = .397, p < .001) when added to the model. Stigma and Self-Esteem uniquely explained 8% of the variance (R² change = .079, p < .001) when added to the model. A person's self-perceived ability to participate and be independent makes a greater contribution to satisfaction with social participation than the frequency of participation. Enhanced understanding of the interplay of subjective and objective factors in influencing participation satisfaction after TBI may result in more effective interventions to support meaningful participation. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

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Study protocol for a feasibility evaluation of Charge Up!: an adaptation of Critical Time Intervention for young adults moving from homelessness to housing

BackgroundYoung adults experiencing homelessness (YAEH) have high rates of mental health challenges, yet low rates of mental health service utilization. The transition from homelessness to housing is a key time for intervention to connect YAEH with mental health treatment and provide support to improve both mental health and housing stability. Charge Up! is a 6-month, phased support intervention that utilizes a team-based approach to connect young adults to community and mental health support. It is an adaptation of Critical Time Intervention that integrates components of Cornerstone, a mental health support intervention designed for young adults.MethodsThis pilot study uses a phased open trial that begins with a feasibility trial to refine the adapted Charge Up! intervention (n = 8), then further tests feasibility, acceptability, and preliminary signal of impact in a small, randomized pilot trial (n = 52). Participants are young adults moving into a transitional housing to rapid rehousing program (TH/RRH) in Houston, Texas. Quantitative interviews are conducted at baseline, 3 months, 6 months, and 12 months. Qualitative interviews are also conducted at 6 months. Exploratory analyses will examine the feasibility of implementing Charge Up!, the performance of measures, and whether Charge Up! is changing the hypothesized targets. Qualitative analysis from interviews will examine demand for the intervention, acceptability of the intervention, and integration of the intervention within the housing system context.DiscussionThe aim of this study is to pilot test Charge Up!, an adapted version of Critical Time Intervention designed to provide targeted support for mental health at the point of transition from homelessness to housing. The Charge Up! intervention was co-developed with young adults and providers, and this phased open trial will help to refine and provide preliminary evidence of the feasibility and acceptability of the intervention. The program is provided in conjunction with a widely used housing model, RRH, and has the potential for scalability as an adjunctive intervention to support youth transitioning into RRH across the United States.Trial registrationThis study was registered on ClinicalTrials.gov on October 20, 2023 (Identifier: NCT06102850), as Protocol ID R34MH129542-01A1, University of Houston, Title: Adaptation of Critical Time Intervention for Young Adults with MH Challenges (CTI-YAMH).

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The effect of low-fat diets on appetite: a systematic review of randomized clinical trials

BackgroundAdherence to low-fat (LF) diets may be inversely associated with appetite; however, findings from available randomized controlled trials (RCTs) are conflicting. The present study aimed to systematically review RCTs assessing the effects of LF diets on appetite status in adult participants.MethodsWe searched PubMed, Scopus, Web of Science, and the Cochrane Library from the inception of the database to June 2, 2024, for RCTs that evaluated the effects of LF diets (≤ 30% total energy from fat), versus high-fat (HF, > 30% total energy from fat) diets on appetite status. No language restrictions were applied.ResultsInitially, 2471 articles were identified, of which nine studies met the inclusion criteria. Seven studies examined the effect of LF diets on hunger response, three of which reported a significantly lower hunger response. LF diets did not exert an effect on satiety, desire to eat, and palatability. Only one study showed that the LF diet, compared to the HF diet, had greater decreases in their total appetite score over a 6-month period.ConclusionsWe found that there were little or no additional benefits in changes to appetite status following LF diets in adults. However, due to methodological factors, shortcomings among studies and small number of studies, the current evidence on the effect of LF diets on appetite regulation is poor. Further long-term trials are needed to investigate the effect of LF diets on appetite and appetite-regulating hormones.

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Flow-induced 2D nanomaterials intercalated aligned bacterial cellulose

Bacterial cellulose is a promising biodegradable alternative to synthetic polymers due to the robust mechanical properties of its nano-fibrillar building blocks. However, its full potential of mechanical properties remains unrealized, primarily due to the challenge of aligning nanofibrils at the macroscale. Additionally, the limited diffusion of other nano-fillers within the three-dimensional nanofibrillar network impedes the development of multifunctional bacterial cellulose-based nanosheets. Here, we report a simple, single-step, and scalable bottom-up strategy to biosynthesize robust bacterial cellulose sheets with aligned nanofibrils and bacterial cellulose-based multifunctional hybrid nanosheets using shear forces from fluid flow in a rotational culture device. The resulting bacterial cellulose sheets display high tensile strength (up to ~ 436 MPa), flexibility, foldability, optical transparency, and long-term mechanical stability. By incorporating boron nitride nanosheets into the liquid nutrient media, we fabricate bacterial cellulose-boron nitride hybrid nanosheets with even better mechanical properties (tensile strength up to ~ 553 MPa) and thermal properties (three times faster rate of heat dissipation compared to control samples). This biofabrication approach yielding aligned, strong, and multifunctional bacterial cellulose sheets would pave the way towards applications in structural materials, thermal management, packaging, textiles, green electronics, and energy storage.

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Applied anatomy and morphology of Meibomian glands in the non-human primate

Dry eye disease (DED) is a common ocular condition that has been estimated to affect ~ 10 to 55.4% of the global population. Symptoms of DED include eye irritation, ocular pain and discomfort, inflammation, and photophobia, and, if left untreated, can lead to infection, corneal neuropathy, corneal scarring and impaired vision. Studies have shown that over 70% of all DED cases are caused by some form of Meibomian gland dysfunction (MGD). To date the etiology of MGD remains unknown, therefore, there is a need for further research into understanding the development, homeostasis and pathology of the Meibomian gland (MG). Various animal models, such as, the murine, rabbit and canine models, have provided valuable insights into the physiopathology of MGD, however, there are many limitations when comparing these models to human MGD. The nonhuman primate (NHP) model is closely related to humans and develops many diseases comparable to humans. This study aimed to characterize the anatomy and morphology of the NHP Macaca mulatta MGs compared to humans. MGs were analyzed by whole mount imaging and histology in the eyelids of NHPs of various ages ranging from ~ 3 months to 12 years. NHPs presented serially arranged MGs within the upper and lower tarsal plate with similar gland morphology to that of humans. Curiously, in the upper lid, the centrally located glands presented a distal portion that is thinner than the remaining glands, with meibocytes directly lining the central collecting duct instead of forming acinar structures. MG atrophy and drop-out were evident in both upper and lower eyelids of NHPs from 6 years of age, increasing in severity with age. Both MG tortuosity and hooking were observed in the NHPs at all ages, being more prevalent in the lower eyelids than in the upper eyelids. Taken together, our findings show that the NHP could be a valuable model for studying MG development, homeostasis and pathology, including Age Related MGD (ARMGD).

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Investigating the thermodynamics properties of water confined in carbon nanotubes using molecular dynamics simulations

Confinement is known to significantly influence the properties of water, yet the precise mechanisms, particularly within nanotubes of varying diameters, remain under investigation. This study examines how confinement impacts the structural and thermodynamic behavior of water molecules inside carbon nanotubes (CNTs) with diameters ranging from 0.8 nm to 3.0 nm, across temperatures from 230 K to 420 K. We present findings on entropy, radial density, self-diffusion coefficients, and orientational order parameters derived from molecular dynamics simulations. Our results reveal that in ultra-narrow 0.8 nm CNTs, water molecules forms a single-file arrangement with some offset molecules, leading in two distinct peaks in the density profile, which differs from earlier reports suggesting a single peak for single-file water. In 0.8 nm CNTs, water demonstrates subdiffusive behavior, whereas larger CNTs show Fickian diffusion. Further analysis reveals a shift from non-Arrhenius to Arrhenius thermodynamic behavior along the CNT axis with increasing temperature. Additionally, a freezing transition of water is observed in 1.0 nm CNTs. Entropy analysis suggests that confined water is more stable than bulk water, though this stability is influenced by the degree of confinement. This study provides deeper insights into the structure and dynamics of water under confinement.

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