Browse Articles

Analytical design and test of a clip-based precision corn seed metering device using DEM-MBD coupling

Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel whose dysfunction leads to intracellular accumulation of chloride ions, dehydration of cell surfaces, and subsequent damage to airway and ductal organs. Beyond its function as a chloride channel, interactions between CFTR, epithelium sodium channel, and solute carrier (SLC) transporter family membrane proteins and cytoplasmic proteins, including calmodulin and Na+/H+ exchanger regulatory factor-1 (NHERF-1), coregulate ion homeostasis. CFTR has also been observed to form mesoscale membrane clusters. However, the contributions of multivalent protein and lipid interactions to cluster formation are not well understood. Using a combination of computational modeling and biochemical reconstitution assays, we demonstrate that multivalent interactions with CFTR protein binding partners, calcium, and membrane cholesterol can induce mesoscale CFTR cluster formation on model membranes. Phosphorylation of the intracellular domains of CFTR also promotes mesoscale cluster formation in the absence of calcium, indicating that multiple mechanisms can contribute to CFTR cluster formation. Our findings reveal that coupling of multivalent protein and lipid interactions promotes CFTR cluster formation consistent with membrane-associated biological phase separation.

Biopsychosocial impact of high levels of trait anxiety on family caregivers in the end-of-life palliative care setting

Introduction Caring for a family member with a palliative diagnosis at home is physically and mentally stressful. This prospective study explores the emotional and physical burdens experienced by family caregivers in end-of-life palliative care settings, particularly focusing on those caregivers with high levels of pre-existing trait anxiety. The following hypotheses were examined: 1.) Family caregivers with high levels of trait anxiety suffer from high levels of anxiety, stress, burnout symptoms, insomnia, daytime sleepiness, physical complaints, health-related anxiety and resentments. 2.) Caregivers with a high level of trait anxiety are less resilient and receive less social support. They are more likely to use inappropriate strategies in the context of emotional regulation and work-related behavior. 3.) The support provided by the mobile palliative care team reduces stress and improves the quality of sleep of the caregiving relatives. Methods Forty-seven caregivers participated, with assessments conducted at two time points: before the mobile palliative care team’s intervention and six weeks later. Data collection included measures such as the State-Trait Anxiety Inventory (STAI), Whiteley Index (WI), Perceived Stress Scale (PSS-10), Maslach Burnout Inventory (MBI-HSS), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Giessen Complaints Questionnaire, Berner Bitterness Inventory (BVI), Brief Resilience Coping Scale, FEEL-E for emotional regulation, AVEM, and the MOS Social Support Survey. Results High levels of trait anxiety among caregivers were significantly associated with increased anxiety, stress, emotional exhaustion, depersonalization, insomnia, and feelings of resentment. Notably, maladaptive emotional regulation strategies were also prevalent. Intervention by the mobile palliative care team significantly reduced stress and insomnia, showing benefits across all levels of trait anxiety. Conclusion Family caregivers with high trait anxiety face significant challenges in end-of-life palliative care settings, indicating a crucial need for early identification and comprehensive biopsychosocial support to mitigate adverse emotional and physical health outcomes.

RNA guanine content and G-quadruplex structure tune the phase behavior and material properties of biomolecular condensates

Cross-reactivity of rPvs48/45, a recombinant Plasmodium vivax protein, with plasma from Plasmodium falciparum endemic areas of Africa

Background Ps48/45, a Plasmodium gametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we explored the cross-reactivity and TB activity of a recombinant P. vivax Ps48/45 protein (rPvs48/45) with plasma from P. falciparum-exposed African donors. Methods rPvs48/45 was produced in Chinese hamster ovary cell lines and tested by ELISA for cross-reactivity with plasma from Burkina Faso, Tanzania, Mali, and Nigeria. In addition, BALB/c mice were immunized with the rPvs48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract of P. falciparum NF-54 gametocytes to evaluate the parasite-boosting effect on rPvs48/45 antibody titers. Specific anti-rPvs48/45 IgG purified from African plasma was used to evaluate the ex vivo TB activity on P. falciparum, using standard mosquito membrane feeding assays (SMFA). Results rPvs48/45 protein showed cross-reactivity with plasma of individuals from all four African countries, in proportions ranging from 94% (Tanzania) to 40% (Nigeria). Also, the level of cross-reactive antibodies varied significantly between countries (p < 0.0001), with a higher antibody level in Mali and the lowest in Nigeria. In addition, antibody levels were higher in adults ( ≥ 17 years) than young children ( ≤ 5 years) in both Mali and Tanzania, with a higher proportion of responders in adults (90%) than in children (61%) (p < 0.0001) in Mali, where male (75%) and female (80%) displayed similar antibody responses. Furthermore, immunization of mice with P. falciparum gametocytes boosted anti-Pvs48/45 antibody responses, recognizing P. falciparum gametocytes in indirect immunofluorescence antibody test. Notably, rPvs48/45 affinity-purified African IgG exhibited a TB activity of 61% against P. falciparum in SMFA. Conclusion Plasma from African volunteers predominantly exposed to P. falciparum cross-recognized the rPvs48/45 protein. This, together with the functional activity of IgG, warrants further studies for the potential development of a P. vivax and P. falciparum cross-protective TB vaccine.

A novel deep sequential learning architecture for drug drug interaction prediction using DDINet

Uncovering the relationship between working memory and performance in the Jigsaw classroom

The Jigsaw classroom is a popular cooperative learning method based on resource interdependence, which requires students to work in small groups on complementary pieces of information, to achieve learning. However, Jigsaw classroom is characterized by contradictory findings and a lack of knowledge on its underlying cognitive mechanisms. The present study examined whether working memory capacity, a key executive function for academic achievement and learning, mediated or moderated the effects of Jigsaw classroom on individual performance. Undergraduate students (n ==  342) attending French University took part in this study (Mage ==  19.40, SD ==  1.21, 60% female). Students worked in small groups on a critical thinking reasoning task, either in the Jigsaw condition or in a cooperative (control) condition without resource interdependence. Working memory was assessed twice, before and during the group activities, by using a complex working memory span task. We analyzed students’ individual score to a quiz on logical fallacies. Multilevel analyses revealed that working memory capacity moderated—but did not mediate—the effect of the Jigsaw classroom. That is, Jigsaw enhanced performance for students with low working memory capacities. These findings offer insight into the potential cognitive mechanisms implied in the success of the Jigsaw method and provide new recommendations for educators on how to redeem the deficit of low working-memory-capacity students on performance.

Determination of optimum extract conditions and evaluation of biological activity potential of Salvia cilicica Boiss

Gut microbiota signatures of the three Mexican primate species, including hybrid populations

Diversity of the gut microbiota has proven to be related with host physiology, health and behavior, influencing host ecology and evolution. Gut microbial community relationships often recapitulate primate phylogeny, suggesting phylosymbiotic associations. Howler monkeys (Alouatta) have been a model for the study of host-gut microbiota relationships, showing the influence of different host related and environmental factors. Differences in life-history traits and feeding behavior with other atelids, like spider monkeys, may reveal distinct patterns of bacterial gut communities, yet few wild populations have been studied; likewise, gut microbiota studies of hybrid populations are mostly lacking. We analyzed diversity and abundance patterns of the gut microbiota of wild populations of the three Mexican primates Ateles geoffroyi, Alouatta palliata and A. pigra from different regions across its distribution in the country, including sympatric localities and the Alouatta hybrid zone. Interspecific differences in gut microbial diversity were higher than intraspecific differences, concordant with phylosymbiosis. Ateles harbored the more differentiated diversity with a major presence of rare taxa, while differences were less strong between Alouatta species. Hybrids had a microbial diversity in-between their parental species, yet also showing unique microbe taxa. Genetic distances between Alouatta individuals correlated positively with their gut microbial dissimilarities. Results show that interspecific and intraspecific overall diversity, abundance and composition patterns are affected by environment, geographic distribution and host genetics. Our study provides the first comprehensive study of gut microbiota of the three Mexican primates and hybrid populations.

Regulating the expression of matrix metalloproteinases to inhibit ovarian carcinoma using isoquinoline alkaloid from Allium ascalonicum

Leveraging machine learning for enhanced and interpretable risk prediction of venous thromboembolism in acute ischemic stroke care

Background Venous thromboembolism (VTE) is a life-threatening complication commonly occurring after acute ischemic stroke (AIS), with an increased risk of mortality. Traditional risk assessment tools lack precision in predicting VTE in AIS patients due to the omission of stroke-specific factors. Methods We developed a machine learning model using clinical data from patients with acute ischemic stroke (AIS) admitted between December 2021 and December 2023. Predictive models were developed using machine learning algorithms, including Gradient Boosting Machine (GBM), Random Forest (RF), and Logistic Regression (LR). Feature selection involved stepwise logistic regression and LASSO, with SHapley Additive exPlanations (SHAP) used to enhance model interpretability. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results Among the 1,632 AIS patients analyzed, 4.17% developed VTE. The GBM model achieved the highest predictive accuracy with an AUC of 0.923, outperforming other models such as Random Forest and Logistic Regression. The model demonstrated strong sensitivity (90.83%) and specificity (93.83%) in identifying high-risk patients. SHAP analysis revealed that key predictors of VTE risk included elevated D-dimer levels, premorbid mRS, and large vessel occlusion, offering clinicians valuable insights for personalized treatment decisions. Conclusion This study provides an accurate and interpretable method to predict VTE risk in patients with AIS using the GBM model, potentially improving early detection rates and reducing morbidity. Further validation is needed to assess its broader clinical applicability.

Hair cortisol as a marker of stress in mild traumatic brain injury: a challenging measure

Signalling strategies and opportunistic behaviour: Insights from dark-net markets

The emergence of social order on darknet markets presents social scientists with a unique puzzle. Because these markets operate outside of conventional regulatory frameworks, there is a lack of legitimate oversight to monitor transactions and protect users from opportunistic behaviour. While existing literature often examines the role of reputation in increasing sales, little attention has been paid to mechanisms that mitigate fraud. This study fills this gap by examining one of the largest known darknet platforms, Alphabay, which was operational from December 2014 to July 2017. Using two Generalised Additive Models (GAMs), results show that costly signals, such as a positive reputation, sellers’ seniority and escrow services, are inversely associated with fraudulent activity on darknet markets. Conversely, cheap signals, such as long product descriptions characterised by complex vocabulary and a positive tone, correlate positively with opportunistic behaviour. The study provides empirical support for signalling theory, by showing that costly signals are more difficult to fake or manipulate and can reduce fraud. Conversely, the study also demonstrates empirically that cheap signals, while potentially effective in initially generating trust among buyers, are associated with an increase in fraud and opportunistic behaviour.

Coastal business perception of coral value and payment for coral restoration

Abstract Coral reefs provide important economic benefits to coastal businesses, supporting recreation and tourism and protecting property from storms. Yet, these benefits are at risk worldwide as corals decline rapidly, and investment in restoration is lacking. With their direct dependence on coral health, coastal businesses may represent an important sector for funding coral restoration; however, it is unclear whether businesses perceive coral reef services as valuable or themselves as reef stewards. We measured business perceptions of coral health and value in Hawaiʻi and identified traits correlated with business decisions to participate in coral restoration at three payment thresholds. We found that businesses see limited economic value in coral reefs. In areas where corals provide substantial ecosystem services (flood protection, tourism revenue), businesses did not consistently rate coral value as high. Nonetheless, businesses showed strong willingness to pay for coral restoration, which was linked to pro-nature motives, reputation, and Native Hawaiian ownership. Results highlight key strategies for engaging private entities in coral restoration.

Livelihood vulnerability index: Assessment of climatic changes in flood affected areas of Mianwali district, Punjab, Pakitan

The world is facing substantial threats from climate change such as extreme weather events, floods, biodiversity loss, sea-level rise, and ecosystem degradation. The objective of this study is to assess the livelihood vulnerability index of communities in flood-prone areas, specifically investigating the reasons behind their vulnerability, their income sources, and the impact of flooding on economic activities. Pakistan is an agrarian country and known to be a climate vulnerable country, flood possess higher threat to rural livelihood. Mianwali district of Punjab, Pakistan was selected as the study area because it is among the poorest districts, and is most severely impacted district during 2010 catastrophe. The study employed qualitative methods like focus group discussions, interviews, and transect walks, alongside quantitative approaches such as the Livelihood Vulnerability Index (LVI). Primary data was collected from 200 households through structured questionnaires by applying simple random sampling technique. Results demonstrated that the overall vulnerability of the local community of Mianwali to flood was high 0.4 score (out of 5) as per Livelihood Vulnerability Index criteria. It was revealed that the exposure factor (0.424) significantly influenced vulnerability and communities had low adaptive capacity (0.077) in the face of flood hazard. While the sensitivity of Mianwali’s community to flood scored 0.088. These findings are crucial for policymakers to assess baseline causes of livelihood vulnerability and formulate adaptation for other rural communities. It can be concluded that addressing these factors effectively in planning strategies may mitigate vulnerability and increase communities’ capacity to deal with potential flooding.

Association between consumption of ultra processed foods and obesity among Jordanian children and adolescents

A riddle of culprit only vs multivessel or immediate vs staged revascularization in patients with non-ST elevation acute coronary syndrome: A meta-analysis

Background Percutaneous coronary intervention (PCI) is a revolutionary breakthrough in saving many lives from myocardial infarction. However, little is known about the PCI strategy in multivessel disease (MVD) Non-ST Elevation Acute Coronary Syndrome (NSTE-ACS) patients. Should complete revascularization be achieved or culprit-only is sufficient, then when the appropriate time of multivessel revascularization is, whether it is staged or immediate. Limited evidence is available on this matter compared to ST-elevation myocardial infarction (STEMI), even though NSTE-ACS patients carry poorer long-term prognoses compared to STEMI. Methods A thorough search for appropriate studies was executed across PubMed, Embase, Medline, Science Direct, and Scopus databases until July 4th, 2023. The risk ratio (RR) underwent analysis through Review Manager 5.4. Results Twenty-six studies with 222,350 MVD NSTE-ACS patients were included. Culprit-only revascularization was significantly related to a higher risk of non-fatal MI (RR: 1.41, 95% CI: 1.04-1.91, p = 0.03, I2: 65%) and all-repeat revascularization (RR 1.86, 95% CI 1.07-3.25, p = 0.03). While multistage multivessel revascularization was related to significantly higher all-cause mortality (RR: 1.73; 95% CI 1.43-2.10; p < 0.01; I2: 0%), TVR repeat (RR 1.38 95% CI 1.11-1.73, I2 =  18%, p = 0.004), and non-TVR repeat (RR 2.59; 95% CI 1,56-4.30; p = 0.0002; I2: 70%). Conclusion Patients with MVD NSTE-ACS treated with multivessel revascularization showed more favorable results than culprit-only. One-stage multivessel revascularization resulted in fewer adverse events than multistage. Additionally, a comprehensive and methodical prospective investigation is required to validate the factors accountable for these outcomes.

Strigolactone insensitivity affects the hormonal homeostasis in barley

Abstract In response to environmental changes, plants continuously make architectural changes in order to optimize their growth and development. The regulation of plant branching, influenced by environmental conditions and affecting hormone balance and gene expression, is crucial for agronomic purposes due to its direct correlation with yield. Strigolactones (SL), the youngest class of phytohormones, function to shape the architecture of plants by inhibiting axillary outgrowth. Barley plants harboring the mutation in the HvDWARF14 (HvD14) gene, which encodes the SL-specific receptor, produce almost twice as many tillers as wild-type (WT) Sebastian plants. Here, through hormone profiling and comparison of transcriptomic and proteomic changes between 2- and 4-week-old plants of WT and hvd14 genotypes, we elucidate a regulatory mechanism that might affect the tillering of SL-insensitive plants. The analysis showed statistically significant increased cytokinin content and decreased auxin and abscisic acid content in ‘bushy’ hvd14 compared to WT, which aligns with the commonly known actions of these hormones regarding branching regulation. Further, transcriptomic and proteomic analysis revealed a set of differentially expressed genes (DEG) and abundant proteins (DAP), among which 11.6% and 14.6% were associated with phytohormone-related processes, respectively. Bioinformatics analyses then identified a series of potential SL-dependent transcription factors (TF), which may control the differences observed in the hvd14 transcriptome and proteome. Comparison to available Arabidopsis thaliana data implicates a sub-selection of these TF as being involved in the transduction of SL signal in both monocotyledonous and dicotyledonous plants.

Clusters and associations of adverse neonatal events with adult risk of multimorbidity: A secondary analysis of birth cohort data

Objective To investigate associations between clustered adverse neonatal events and later-life multimorbidity. Design Secondary analysis of birth cohort data. Setting Prospective birth cohort study of individuals born in Britain in one week of 1970. Population Respondents provided data at birth (n = 17,196), age 34 (n = 11,261), age 38 (n = 9,665), age 42 (n = 9,840), and age 46 (n = 8,580). Methods Mixed components analysis determined included factors, ‘Birthweight’; ‘Neonatal cyanosis’; ‘Neonatal cerebral signs’; ‘Neonatal illnesses’; ‘Neonatal breathing difficulties’; and ‘Prolonged duration to establishment of respiratory rate at birth’, within the composite adverse neonatal event score. Log-binomial regression quantified the unadjusted and covariate-adjusted (paternal employment status and social class; maternal smoking status; maternal age; parity; cohort member smoking status and Body Mass Index) associations between the adverse neonatal event score and risk of multimorbidity in adulthood. Outcome measures Multimorbidity at each adult data sweep, defined as the presence of two or more Long-Term Conditions (LTCs). Results 13.7% of respondents experienced one or more adverse neonatal event(s) at birth. The percentage reporting multimorbidity increased steadily from 14.6% at age 34 to 25.5% at age 46. A significant association was only observed at the 38 years sweep; those who had experienced two or more adverse neonatal events had a 41.0% (95% CI: 1.05 – 1.88) increased risk of multimorbidity, compared to those who had not suffered any adverse neonatal events at birth. This association was maintained following adjustment for parental confounders and adult smoking status. Conclusions Adverse neonatal events at birth may be independently associated with the development of midlife multimorbidity. Programmes and policies aimed at tackling the growing public health burden of multimorbidity may also need to consider interventions to reduce adverse neonatal events at birth.

RETRACTED ARTICLE: Synthesis, antimicrobial, anti-inflammatory, antioxidant and cytotoxicity of new pyrimidine and pyrimidopyrimidine derivatives

Abstract A series of novel pyrimidine and pyrimidopyrimidine analogs were synthesized in good yield from 6-amino-4-aryl-2-oxo-pyrimidine-5-carbonitrile ( 1a-d ). The synthesized compounds were characterized using various spectral studies, including FT-IR, 1 H NMR, 13 C NMR, mass spectrometry, and elemental analysis. Newly synthesized pyrimidopyrimidines and 2-(substituted-pyrazolyl)pyrimidine derivatives were assessed in vitro for their cytotoxic activities against three cancerous cell lines: colorectal carcinoma ( HCT-116 ), mammary gland breast cancer ( MCF-7 ), and hepatocellular carcinoma ( HEPG-2 ), as well as normal fibroblasts ( W138 ). The results indicated that compounds 3b , 10b , and 10c exhibited the highest cytotoxic activities, with IC 50 values very close to those of the reference drug (doxorubicin) across all studied cancerous cell lines, while also demonstrating good safety effects on the normal human lung fibroblast cell line. Furthermore, all the synthesized compounds were examined for their antimicrobial activity against two Gram-positive bacteria ( Staphylococcus aureus and Bacillus subtilis ), one Gram negative bacterium ( Escherichia coli ) and two fungal species ( Candida albicans and Aspergillus flavus ). The antimicrobial results of the synthesized compounds, when compared with the reference drugs ampicillin and clotrimazole, revealed that compounds 3a , 3b , 3d , 4a-d , 9c and 10b exhibited excellent antimicrobial activities. Moreover, membrane stabilization or anti-hemolytic activity was employed as a method to study the in vitro anti-inflammatory activity of the prepared heterocyclic compounds. Antioxidant activities were also assessed by measuring the percentage of free radical scavenging. Compounds 4b , 10c and 11a-c demonstrated strong anti-hemolytic and antioxidant effects, which can be attributed to their ability to protect red blood cells from hemolysis.