pKa Calculations of GPCRs: Understanding Protonation States in Receptor Activation.

The increase in the available G protein-coupled receptor (GPCR) structures has been pivotal in helping to understand their activation process. However, the role of protonation-conformation coupling in GPCR activation still needs to be clarified. We studied the protonation behavior of the highly conserved Asp2.50 residue in five different class A GPCRs (active and inactive conformations) using a linear response approximation (LRA) pKa calculation protocol. We observed consistent differences (1.3 pK units) for the macroscopic pKa values between the inactive and active states of the A2AR and B2AR receptors, indicating the protonation of Asp2.50 during GPCR activation. This process seems to be specific and not conserved, as no differences were observed in the pKa values of the remaining receptors (CB1R, NT1R, and GHSR).

SCI1, a flower regulator of cell proliferation, and its partners NtCDKG2 and NtRH35 interact with the splicing machinery.

Successful plant reproduction depends on the adequate development of flower organs controlled by cell proliferation and other processes. The SCI1 gene regulates cell proliferation and affects the final size of the female reproductive organ. To unravel the molecular mechanism exerted by SCI1 in cell proliferation control, we searched for its interaction partners through semi-in vivo pulldown experiments, uncovering a cyclin-dependent kinase, NtCDKG;2. Bimolecular fluorescence complementation (BiFC) and co-localization experiments showed that SCI1 interacts with NtCDKG;2 and its cognate NtCyclin L in nucleoli and splicing speckles. The screening of a yeast two-hybrid (Y2H) cDNA library using SCI1 as bait revealed a novel DEAD-box RNA helicase (NtRH35). The interaction between the NtCDKG;2-NtCyclin L complex, and NtRH35 was also shown. Subcellular localization experiments showed that SCI1, NtRH35, and the NtCDKG;2-NtCyclin L complex associate with each other within splicing speckles. The Y2H screening of NtCDKG;2 and NtRH35 identified the conserved spliceosome components U2a', NKAP, and CACTIN. This work presents SCI1 and its interactors NtCDKG;2-NtCyclin L complex, and NtRH35 as new spliceosome-associated proteins. Our findings reveal a network of interactions and suggest that SCI1 may regulate cell proliferation through the splicing process. This study provides new valuable insights into the intricate molecular pathways governing plant development.

Did I tell you something personal? The influence of the distinctive features on destination memory.

Several studies observed that a worse destination memory (i.e., capacity to remember to whom we said something) occurs when personal facts are shared, which was explained based on the internal attentional focus - the attentional focus is on the information and not on the recipient of the information. So, with two experiments, we aimed to mitigate the negative influence of the internal attentional focus on destination memory. Since it was previously observed that sharing information with distinctive faces leads to a better destination memory, in Experiment 1, participants (N = 30) were asked to transmit personal facts to distinctive and undistinctive faces. No differences were observed. To increase the attentional focus on the recipient of the information, in Experiment 2, participants (N = 30) were also asked to evaluate the distinctiveness of the recipients' faces. A better destination memory was not observed in Experiment 2 compared with Experiment 1. This leads us to conclude that asking participants to evaluate the faces did not promote a better destination memory when personal facts were shared. Nevertheless, by asking to evaluate the faces, the attentional focus was on the faces, where distinctive faces attracted more attention and led to a better destination memory.

Missed Opportunity or Cause for Concern? Methamphetamine Use Is Associated With Greater Interest in Event-Driven PrEP Among Sexual Minority Men.

Our study assessed the association between methamphetamine (i.e., crystal meth, CM) use and awareness and interest in event-driven (ED) PrEP among HIV-negative and those with unknown serostatus cisgender males and transgender people. We performed log-binomial regression analysis to predict awareness (i.e., having heard of ED PrEP) and being interested in ED PrEP. We found that participants who recently used CM were less likely to know of ED PrEP (aPR = 0.83, 95% CI [0.69, 0.99]) but more interested in ED PrEP (aPR = 1.12, 95% CI [1.01, 1.30]), after accounting for demographic and HIV-related behaviors. Opportunities to expand PrEP uptake and improve adherence among individuals who report CM use are essential to impact the HIV epidemic significantly. Continued research on the needs and best practices to work with this community is needed to ensure a successful rollout and implementation of ED PrEP.

Prospects and challenges in using neuronal extracellular vesicles in biomarker research.

Extracellular vesicles (EVs) hold promise as a source of disease biomarkers. The diverse molecular cargo of EVs can potentially indicate the status of their tissue of origin, even against the complex background of whole plasma. The main tools currently available for assessing biomarkers of brain health include brain imaging and analysis of the cerebrospinal fluid of patients. Given the costs and difficulties associated with these methods, isolation of EVs of neuronal origin (NEVs) from the blood is an attractive approach to identify brain-specific biomarkers. This perspective describes current key challenges in EV- and NEV-based biomarker research. These include the relative low abundance of EVs, the lack of validated isolation methods, and the difficult search for an adequate target for immunocapturing NEVs. We discuss that these challenges must be addressed before NEVs can fulfill their potential for biomarker research. HIGHLIGHTS: NEVs are promising sources of biomarkers for brain disorders. Immunocapturing NEVs from complex biofluids presents several challenges. The choice of surface target for capture will determine NEV yield. Contamination by non-EV sources is relevant for biomarkers at low concentrations.

Associations between domains of sedentary behavior, well-being, and quality of life - a cross-sectional study.

The importance of reducing sedentary behavior (SB) in the prevention of mortality and chronic and mental diseases is scientifically well grounded, but SB can be accumulated in diverse domains of life, such as leisure-time SB, transport between home/work/school when sitting (transport-related SB), or in occupational settings such as working or studying (occupational SB), and the associations for each domain of SB with well-being measures and quality of life are still underexplored from a positive perspective. Through a cross-sectional investigation, we collected data from 584 participants who completed a questionnaire throughout November 2021 and with Spearman correlation test, analysed the associations between SB in three different domains with psychological well-being, satisfaction with life, and quality of life. Our results indicated that after adjustment for physical activity, sex, body mass index, smoking history, chronic disease status, financial perception, quality/duration of sleep and university group, in younger adults (18 to 24 years old), leisure-time SB was negatively related to psychological well-being (rho = -0.255; p = 0.008), and in adults (25 to 64 years old), occupational SB was negatively related to satisfaction with life (rho = -0.257; p < .001) and the mental component of quality of life (rho = -0.163; p = 0.027). Our findings highlight the idea that not all SB is built the same and that future strategies to reduce SB from people's lives must target specific domains of SB according to the age group when aiming to improve well-being and quality of life.

[Ag(IPr)(bpy)][PF6]: brightness and darkness playing with aggregation induced phosphorescence for light-emitting electrochemical cells.

Heteroleptic silver(I) complexes have recently started to attract attention in thin-film lighting technologies as an alternative to copper(I) analogues due to the lack of flattening distortion upon excitation. However, the interpretation of their photophysical behavior is challenging going from traditional fluorescence/phosphorescence to a temperature-dependent dual emission mechanism and ligand-lock assisted thermally activated delayed fluorescence. Herein, we unveil the photoluminescence behavior of a three-coordinated Ag(I) complex with the N-heterocyclic carbene (NHC) ligand and 2,2'-bipyridine (bpy) as the N^N ligand. In contrast to its low-emissive Cu(I) complex structural analogues, a strong greenish emission was attributed to the presence of aggregates formed by π-π intermolecular interactions as revealed by the X-ray structure and aggregation induced emission (AIE) studies in solution. In addition, the temperature-dependent time-resolved spectroscopic and computational studies demonstrated that the emission mechanism is related to a phosphorescence emission mechanism of two very close lying (ΔE = 0.08 eV) excited triplet states, exhibiting a similar delocalized nature over the bipyridine ligands. Unfortunately, this favourable AIE is lost upon forming homogeneous thin films suitable for lighting devices. Though the films showed very poor emission, the electrochemical stability under device operation conditions is remarkable compared to the prior-art, highlighting the potential of [Ag(NHC)(N^N)][X] complexes in thin-film lighting.

Striking genetic homogeneity in the widespread South American bracken.

PREMISE: Bracken (Pteridium, Dennstaedtiaceae) is a cosmopolitan genus of aggressive disturbance colonizers that are toxic to agricultural livestock. The taxonomy of Pteridium has been treated in multiple schemes, ranging from one to six species worldwide, with numerous subspecies and varieties. Recent work has focused on the worldwide distribution and systematics of the bracken fern, but South America has been poorly represented. We present the first continent-wide sampling and analysis of Pteridium esculentum, a Southern Hemisphere diploid species. METHODS: Within South America, P. esculentum has several morphotypes, distinguished into subspecies by variation in indument and lamina architecture. We used double digest restriction site-associated DNA sequencing (ddRADSeq) to assess the phylogenetic relationships of P. esculentum subspecies. RESULTS: We found a striking genetic homogeneity in the species, being able to support only two morphotypes from molecular data: P. e. arachnoideum and P. e. campestre. We had high confidence for shallow and deep phylogenetic relationships, but less support for relationships among crown groups. CONCLUSIONS: We describe an east-west geographic pattern that would explain the relationships between populations; and, in contrast to previous studies, we detected differences with P. esculentum from Australia. These results will lay the foundations for studying variations in this species' behavior as a weed, as well as its impact on the production of agricultural livestock in South America.

Building Capacity of Community Health Centers to Improve the Provision of Postpartum Care Services Through Data-Driven Health Information Technology and Innovation.

Maternal morbidity and mortality remain significant challenges in the United States, with substantial burden during the postpartum period. The Centers for Disease Control and Prevention, in partnership with the National Association of Community Health Centers, began an initiative to build capacity in Federally Qualified Health Centers to (1) improve the infrastructure for perinatal care measures and (2) use perinatal care measures to identify and address gaps in postpartum care. Two partner health center-controlled networks implemented strategies to integrate evidence-based recommendations into the clinic workflow and used data-driven health information technology (HIT) systems to improve data standardization for quality improvement of postpartum care services. Ten measures were created to capture recommended care and services. To support measure capture, a data cleaning algorithm was created to prioritize defining pregnancy episodes and delivery dates and address data inconsistencies. Quality improvement activities targeted postpartum care delivery tailored to patients and care teams. Data limitations, including inconsistencies in electronic health record documentation and data extraction practices, underscored the complexity of integrating HIT solutions into postpartum care workflows. Despite challenges, the project demonstrated continuous quality improvement to support data quality for perinatal care measures. Future solutions emphasize the need for standardized data elements, collaborative care team engagement, and iterative HIT implementation strategies to enhance perinatal care quality. Our findings highlight the potential of HIT-driven interventions to improve postpartum care within health centers, with a focus on the importance of addressing data interoperability and documentation challenges to optimize and monitor initiatives to improve postpartum health outcomes.

Dislocation Density-Mediated Functionality in Single-Crystal BaTiO3.

Unlike metals where dislocations carry strain singularity but no charge, dislocations in oxide ceramics are characterized by both a strain field and a local charge with a compensating charge envelope. Oxide ceramics with their deliberate engineering and manipulation are pivotal in numerous modern technologies such as semiconductors, superconductors, solar cells, and ferroics. Dislocations facilitate plastic deformation in metals and lead to a monotonous increase in the strength of metallic materials in accordance with the widely recognized Taylor hardening law. However, achieving the objective of tailoring the functionality of oxide ceramics by dislocation density still remains elusive. Here a strategy to imprint dislocations with {100}<100> slip systems and a tenfold change in dislocation density of BaTiO3 single crystals using high-temperature uniaxial compression are reported. Through a dislocation density-based approach, dielectric permittivity, converse piezoelectric coefficient, and alternating current conductivity are tailored, exhibiting a peak at medium dislocation density. Combined with phase-field simulations and domain wall potential energy analyses, the dislocation-density-based design in bulk ferroelectrics is mechanistically rationalized. These findings may provide a new dimension for employing plastic strain engineering to tune the electrical properties of ferroics, potentially paving the way for advancing dislocation technology in functional ceramics.

Double outlet right atrium in a dog.

Double outlet right atrium is a rare congenital cardiac abnormality that has been previously reported in humans and cats, but not in dogs. A double outlet right atrium is typically characterized by the presence of a leftward deviation of the interatrial septum and atrial septal defect. Therefore, the right atrium drains into both ventricles. The unique features consistent with double outlet right atrium were identified by transthoracic echocardiography and computed tomography in a puppy. This case report describes the clinical, echocardiographic, and tomographic findings of a five-month-old Cocker Spaniel diagnosed with this rare congenital abnormality.

Improved Treatment Outcome Following the Use of a Wound Dressings in Cutaneous Leishmaniasis Lesions.

Leishmaniasis, caused by Leishmania parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development of better alternatives. Bacterial NanoCellulose (BNC), a biocompatible nanomaterial, has unique properties regarding wound healing. In a previous study, we showed that use of topical BNC + systemic MA significantly increased the cure rate of CL patients, compared to treatment with MA alone. Herein, we performed a study comparing the combination of a wound dressing (BNC or placebo) plus systemic MA versus systemic MA alone, in CL caused by Leishmania braziliensis. We show that patients treated with the combination treatment (BNC or placebo) + MA showed improved cure rates and decreased need for rescue treatment, although differences compared to controls (systemic MA alone) were not significant. However, the overall time-to-cure was significantly lower in groups treated with the combination treatment (BNC+ systemic MA or placebo + systemic MA) in comparison to controls (MA alone), indicating that the use of a wound dressing improves CL treatment outcome. Assessment of the immune response in peripheral blood showed an overall downmodulation in the inflammatory landscape and a significant decrease in the production of IL-1a (p < 0.05) in patients treated with topical BNC + systemic MA. Our results show that the application of wound dressings to CL lesions can improve chemotherapy outcome in CL caused by L. braziliensis.

Intramolecular singlet fission: Quantum dynamical simulations including the effect of the laser field.

In the previous work [Reddy et al., J. Chem. Phys. 151, 044307 (2019)], we have analyzed the dynamics of the intramolecular singlet fission process in a series of prototypical pentacene-based dimers, where the pentacene monomers are covalently bonded to a phenylene linker in ortho, meta, and para positions. The results obtained were qualitatively consistent with the experimental data available, showing an ultrafast population of the multiexcitonic state that mainly takes place via a mediated (superexchange-like) mechanism involving charge transfer and doubly excited states. Our results also highlighted the instrumental role of molecular vibrations in the process as a sizable population of the multiexcitonic state could only be obtained through vibronic coupling. Here, we extend these studies and investigate the effect of the laser field on the dynamics of intramolecular singlet fission by explicitly including the coupling to the laser field in our model. In this manner, and by selectively tuning the laser field to the different low-lying absorption bands of the systems investigated, we analyze the wavelength dependence of the intramolecular singlet fission process. In addition, we have also analyzed how the nature of the initially photoexcited electronic state (either localized or delocalized) affects its dynamics. Altogether, our results provide new insights into the design of intramolecular singlet fission-active molecules.

The effectiveness of a 6-month intervention with sit-stand workstation in office workers: Results from the SUFHA cluster randomized controlled trial.

BACKGROUND: Prolonged periods of sitting have been linked to negative health outcomes. Implementation of sit-stand desks in the workplace has been one strategy to reduce prolonged sitting. OBJECTIVE: To assess the effectiveness of sit-stand workstations on reducing sitting time and improving other health outcomes of office-based workers. METHODS: 39 Portuguese office workers were randomized into a 6-month parallel-group cluster RCT consisting by the implementation of sit-stand desks in the workplace. The primary outcome of sitting time was assessed using ActivPAL. Secondary outcomes included biometric, psychological, and diet-related variables. All outcomes were assessed at baseline and 6 months for the whole sample and at 3 months for a sub-sample of the intervention group (n = 11). RESULTS: No significant time*group interaction was found for the primary or secondary outcomes, apart from waist circumference favoring the control group (Δ-1.81 cm, pinteraction = 0.04). There were significant changes within the intervention group for sitting time (-44.0 min/day), prolonged sitting (>30 min) (-45.3 min/day) and standing time (51.7 min/day) at 3 months in the sub-sample and in prolonged sitting (>30 min) (-26 min/day) in the full intervention group (p < 0.05). Changes were also observed within the intervention group for percent body fat (Δ-3.7%) and ratings of quality of life (Δ2.2), musculoskeletal discomfort (Δ-4.9), overall fatigue (Δ-2.2), and the need for recovery after work (Δ-1.7) at 6-month follow-up (p < 0.05). CONCLUSION: Although not being effective for reducing sitting time, the implementation of sit-stand desks in the Portuguese workspace was shown to be feasible over the long term, received well by users, and may offer other health benefits. TRIAL REGISTRATION: OSF Registration, OSF.IO/JHGPW. Registered 15 November 2022. https://doi.org/10.17605/OSF.IO/JHGPW.

PypKa server: online pKa predictions and biomolecular structure preparation with precomputed data from PDB and AlphaFold DB.

When preparing biomolecular structures for molecular dynamics simulations, pKa calculations are required to provide at least a representative protonation state at a given pH value. Neglecting this step and adopting the reference protonation states of the amino acid residues in water, often leads to wrong electrostatics and nonphysical simulations. Fortunately, several methods have been developed to prepare structures considering the protonation preference of residues in their specific environments (pKa values), and some are even available for online usage. In this work, we present the PypKa server, which allows users to run physics-based, as well as ML-accelerated methods suitable for larger systems, to obtain pKa values, isoelectric points, titration curves, and structures with representative pH-dependent protonation states compatible with commonly used force fields (AMBER, CHARMM, GROMOS). The user may upload a custom structure or submit an identifier code from PBD or UniProtKB. The results for over 200k structures taken from the Protein Data Bank and the AlphaFold DB have been precomputed, and their data can be retrieved without extra calculations. All this information can also be obtained from an application programming interface (API) facilitating its usage and integration into existing pipelines as well as other web services. The web server is available at pypka.org.

The role of cue salience in prospective memory commission errors in nonperformed nonfocal tasks.

Prospective memory (PM) refers to the ability to remember to execute an intention in the future without having a permanent reminder. These intentions can be performed when they are not relevant or become no-longer needed, the so-called "commission errors". The present study aims to understand the effect of cue salience on PM commission errors with unperformed intentions and on the ongoing task performance-associated costs. Through a between-subjects design, eighty-one participants were assigned to 3 conditions: the no-PM condition, which served as control, and the salient and nonsalient conditions, which were asked to perform a lexical decision task and an incomplete nonfocal prospective memory task (i.e. no PM cues were presented). Subsequently, participants were instructed to no longer execute the prospective intention. In the second phase, a lexical decision task occurred again, including irrelevant PM cues, which should not be answered as such. In the salient condition, cues were salient (i.e. presented in red or blue background). In contrast, in the nonsalient condition, PM cues appeared on a black background, as any other stimuli. In the no-PM control condition, participants only performed an LDT. A commission error occurred when the (irrelevant) intention was performed in this second phase. Results showed that more participants performed a commission error in the presence of salient cues, even when PM intentions became irrelevant. Additionally, when cues were not salient, participants took longer to answer the LDT, as reasoned by the spontaneous retrieval theory. These findings are discussed according to the dual-mechanism account.

PrEP Uptake and Methamphetamine Use Patterns in a 4-Year U.S. National Prospective Cohort Study of Sexual and Gender Minority People, 2017-2022.

Methamphetamine use is on the rise among sexual and gender minority people who have sex with men (SGMSM), escalating their HIV risk. Despite pre-exposure prophylaxis (PrEP) being an effective biomedical HIV prevention tool, its uptake in relation to methamphetamine use patterns in SGMSM has not been studied. In a U.S. cohort study from 2017 to 2022, 6,253 HIV-negative SGMSM indicated for but not using PrEP were followed for four years. Methamphetamine use was categorized (i.e., newly initiated, persistently used, never used, used but quit), and PrEP uptake assessed using generalized estimating equation (GEE), adjusted for attrition. Participants had a median age of 29, with 51.9% White, 11.1% Black, 24.5% Latinx, and 12.5% other races/ethnicities. Over the four years, PrEP use increased from 16.3 to 27.2%. GEE models identified risk factors including housing instability and food insecurity. In contrast, older age, health insurance, clinical indications, and prior PrEP use increased uptake. Notably, Latinx participants were more likely to use PrEP than Whites. Regarding methamphetamine use, those who newly initiated it were more likely to use PrEP compared to non-users. However, those who quit methamphetamine and those who persistently used it had PrEP usage rates comparable to those of non-users. Though PrEP uptake increased, it remained low in SGMSM. Methamphetamine use was associated with PrEP uptake. Healthcare providers should assess methamphetamine use for harm reduction. Prioritizing younger, uninsured SGMSM and addressing basic needs can enhance PrEP uptake and reduce HIV vulnerabilities.

Dietary metabarcoding reveals the simplification of bird-pest interaction networks across a gradient of agricultural cover.

Agriculture is vital for supporting human populations, but its intensification often leads to landscape homogenization and a decline in non-provisioning ecosystem services. Ecological intensification and multifunctional landscapes are suggested as nature-based alternatives to intensive agriculture, using ecological processes like natural pest regulation to maximize food production. Birds are recognized for their role in increasing crop yields by consuming invertebrate pests in several agroecosystems. However, the understanding of how bird species, their traits and agricultural land cover influence the structure of bird-pest interactions remains limited. We sampled bird-pest interactions monthly for 1 year, at four sites within a multifunctional landscape, following a gradient of increasing agricultural land cover. We analysed 2583 droppings of 55 bird species with DNA metabarcoding and detected 225 pest species in 1139 samples of 42 bird species. As expected, bird-pest interactions were highly variable across bird species. Dietary pest richness was lower in the fully agricultural site, while predation frequency remained consistent across the agricultural land cover gradient. Network analysis revealed a reduction in the complexity of bird-pest interactions as agricultural coverage increased. Bird species abundance affected the bird's contribution to the network structure more than any of the bird traits analysed (weight, phenology, invertebrate frequency in diet and foraging strata), with more common birds being more important to network structure. Overall, our results show that increasing agricultural land cover increases the homogenization of bird-pest interactions. This shows the importance of maintaining natural patches within agricultural landscapes for biodiversity conservation and enhanced biocontrol.

A agricultura é essencial para suportar a população humana, mas a sua intensificação geralmente leva à homogeneização da paisagem e à redução dos serviços do ecossistema que não sejam de provisão. A intensificação ecológica e paisagens multifuncionais são sugeridas como alternativas naturais à agricultura intensiva, utilizando processos ecológicos como a regulação natural de pragas para maximizar a produção de alimentos. As aves são conhecidas pelo seu papel no aumento da produtividade das culturas por consumirem pragas em diversos agroecossistemas. Contudo, o conhecimento de como as espécies de aves, as suas características e a cobertura agrícola influenciam as interações entre aves e pragas são limitados. Nós amostrámos estas interações mensalmente durante um ano, em quatro locais, numa paisagem multifuncional, ao longo um gradiente de aumento da cobertura agrícola. Analisamos 2583 dejetos de 55 espécies de aves com DNA metabarcoding e detetamos 225 espécies praga em 1139 amostras de 42 espécies de aves. Como esperado, as interações entre aves e pragas foram muito distintas entre as várias espécies de aves. A riqueza de pragas na dieta foi menor no local completamente dominado por área agrícola, enquanto a frequência de predação de pragas foi constante ao longo do gradiente de cobertura agrícola. A análise de redes demonstrou uma redução na complexidade das interações entre aves e pragas à medida que a cobertura agrícola aumenta. A abundância das espécies de aves influenciou mais a contribuição das aves para a estrutura da rede do que qualquer uma das características analisadas (peso, fenologia, frequência de invertebrados na dieta e estrato de alimentação), sendo as aves mais comuns as mais importantes na estrutura da rede. De forma geral, os nossos resultados indicam que o aumento da cobertura agrícola aumenta a homogeneização das interações entre aves e pragas. Isto demonstra a importância de preservar áreas naturais em paisagem agrícolas para a conservação de biodiversidade e melhor controlo biológico.