Miracle-dz/UniFAR-FTUs huggingface dataset:
Wnt-Ror-Dvl signalling and the dystrophin complex organize planar-polarized membrane compartments in C. elegans muscles

Cell polarity mechanisms allow the formation of specialized membrane domains with unique protein compositions, signalling properties, and functional characteristics. By analysing the localization of potassium channels and proteins belonging to the dystrophin-associated protein complex, we reveal the existence of distinct planar-polarized membrane compartments at the surface of C. elegans muscle cells. We find that muscle polarity is controlled by a non-canonical Wnt signalling cascade involving the ligand EGL-20/Wnt, the receptor CAM-1/Ror, and the intracellular effector DSH-1/Dishevelled. Interestingly, classical planar cell polarity proteins are not required for this process. Using time-resolved protein degradation, we demonstrate that –while it is essentially in place by the end of embryogenesis– muscle polarity is a dynamic state, requiring continued presence of DSH-1 throughout post-embryonic life. Our results reveal the unsuspected complexity of the C. elegans muscle membrane and establish a novel genetically tractable model system to study cellular polarity and membrane compartmentalization in vivo.
Phospho-seq: Integrated, multi-modal profiling of intracellular protein dynamics in single cells

Cell signaling plays a critical role in regulating cellular behavior and fate. While multimodal single-cell sequencing technologies are rapidly advancing, scalable and flexible profiling of cell signaling states alongside other molecular modalities remains challenging. Here we present Phospho-seq, an integrated approach that aims to quantify phosphorylated intracellular and intranuclear proteins, and to connect their activity with cis-regulatory elements and transcriptional targets. We utilize a simplified benchtop antibody conjugation method to create large custom antibody panels for simultaneous protein and scATAC-seq profiling on whole cells, and integrate this information with scRNA-seq datasets via bridge integration. We apply our workflow to cell lines, induced pluripotent stem cells, and 3-month-old brain organoids to demonstrate its broad applicability. We demonstrate that Phospho-seq can define cellular states and trajectories, reconstruct gene regulatory relationships, and characterize the causes and consequences of heterogeneous cell signaling in neurodevelopment.
Analysis of an accessibility strategy for deaf people: Videos on a traveling science center

Introduction Brazilian traveling science centers have difficulties in providing sign language accessibility to the deaf people that visit them. The main objective of this study was to analyze the contribution of accessible video guides in Brazilian Sign Language (BSL) in helping deaf visitors understand the activities proposed by the traveling science center “Ciências Sob Tendas”. Methods This research used a critical quali-quantitative approach that involved 128 deaf students from middle and high schools. Data were gathered via an online survey and video recording. Results and discussion The results indicated successful use of the video guides by deaf participants. Within this specific research, in which 745 questionnaires were answered, we found that the videos, along with interactive activities, contributed to the interest, curiosity, and understanding of the themes presented. Furthermore, the return visits of deaf people to revisit activities a second and third time may indicate the potential of this science communication strategy to stimulate their interest in scientific knowledge. However, 15% of responses showed that they had some difficulty understanding the video's explanation. This may indicate that, although videos are a well-accepted alternative for accessibility, the presence of an interpreter guide or a deaf visitor guide, when possible, is ideal. Essentially, a professional interpreter can use several BSL resources and strategies to make themselves understood. Conclusion Thus, we considered that accessible video guides in BSL are a viable resource for providing accessibility to deaf people in traveling science centers.
Targeted insertion of regulatory elements enables translational enhancement in rice

In-locus editing of agronomically-important genes to optimize their spatiotemporal expression is becoming an important breeding approach. Compared to intensive studies on mRNA transcription, manipulating protein translation by genome editing has not been well exploited. Here, we found that precise knock-in of a regulating element into the 5’UTR of a target gene could efficiently increase its protein abundance in rice. We firstly screened a translational enhancer (AMVE) from alfalfa mosaic virus using protoplast-based luciferase assays with an 8.5-folds enhancement. Then the chemically modified donor of AMVE was synthesized and targeted inserted into the 5’UTRs of two genes (WRKY71 and SKC1) using CRISPR/Cas9. Following the in-locus AMVE knock-in, we observed up to a 2.8-fold increase in the amount of WRKY71 protein. Notably, editing of SKC1, a sodium transporter, significantly increased salt tolerance in T2 seedlings, indicating the expected regulation of AMVE knock-in. These data demonstrated the feasibility of such in-locus editing to enhance protein expression, providing a new approach to manipulating protein translation for crop breeding.
Metagenomic assessment of nitrate-contaminated mine wastewaters and optimization of complete denitrification by indigenous enriched bacteria

Nitrate contamination in water remains to be on the rise globally due to continuous anthropogenic activities, such as mining and farming, which utilize high amounts of ammonium nitrate explosives and chemical-NPK-fertilizers, respectively. This study presents insights into the development of a bioremediation strategy to remove nitrates (NO3 −) using consortia enriched from wastewater collected from a diamond mine in Lesotho and a platinum mine in South Africa. A biogeochemical analysis was conducted on the water samples which aided in comparing and elucidating their unique physicochemical parameters. The chemical analysis uncovered that both wastewater samples contained over 120 mg/L of NO3 − and over 250 mg/L of sulfates (SO4 2-), which were both beyond the acceptable limit of the environmental surface water standards of South Africa. The samples were atypical of mine wastewaters as they had low concentrations of dissolved heavy metals and a pH of over 5. A metagenomic analysis applied to study microbial diversities revealed that both samples were dominated by the phyla Proteobacteria and Bacteroidetes, which accounted for over 40% and 15%, respectively. Three consortia were enriched to target denitrifying bacteria using selective media and then subjected to complete denitrification experiments. Denitrification dynamics and denitrifying capacities of the consortia were determined by monitoring dissolved and gaseous nitrogen species over time. Denitrification optimization was carried out by changing environmental conditions, including supplementing the cultures with metal enzyme co-factors (iron and copper) that were observed to promote different stages of denitrification. Copper supplemented at 50 mg/L was observed to be promoting complete denitrification of over 500 mg/L of NO3 −, evidenced by the emission of nitrogen gas (N2) that was more than nitrous oxide gas (N2O) emitted as the terminal by-product. Modification and manipulation of growth conditions based on the microbial diversity enriched proved that it is possible to optimize a bioremediation system that can reduce high concentrations of NO3 −, while emitting an environmentally-friendly N2 instead of N2O, that is, a greenhouse gas. Data collected and discussed in this research study can be used to model an upscale NO3 − bioremediation system aimed to remove nitrogenous and other contaminants without secondary contamination.
Cardiovascular outcomes after curative prostate cancer treatment: A population-based cohort study

Objective To investigate differences in cardiovascular disease (CVD) morbidity and mortality after radical prostatectomy or definitive radiotherapy with or without androgen deprivation therapy (ADT). Materials and methods We used population-based data from the Cancer Registry of Norway, the Norwegian Patient Registry and the Norwegian Cause of Death Registry including 19 289 men ≤80 years diagnosed with non-metastatic prostate cancer during 2010-2019. Patients were treated with radical prostatectomy or definitive radiotherapy. We used competing risk models to compare morbidity from overall CVD, acute myocardial infarction (AMI), cerebral infarction, thromboembolism, and CVD-specific mortality for the overall cohort and stratified by prognostic risk groups. Results After a median follow-up time of 5.4 years (IQR 4.6 years), there were no differences in adjusted rates of AMI, cerebral infarction, and CVD-specific death between radical prostatectomy and definitive radiotherapy in any of the prognostic risk groups. Rates of overall CVD (0.82; 95% CI 0.76-0.89) and thromboembolism (0.30; 95% CI 0.20-0.44) were lower for definitive radiotherapy than radical prostatectomy during the first year of follow-up. After this overall CVD rates (1.19; 95% CI 1.11-1.28) were consistently higher across all risk groups in patients treated with definitive radiotherapy, but there were no differences regarding thromboembolism. Conclusions During the first years after treatment, no differences were found in rates of AMI, cerebral infarction, and CVD-specific death between radiotherapy and radical prostatectomy in any of the prognostic risk groups. This suggests that ADT use in combination with radiotherapy may not increase the risks of these outcomes in a curative setting. The increased overall CVD rate for definitive radiotherapy after the first year indicates a possible relationship between definitive radiotherapy and other CVDs than AMI and cerebral infarction.
Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients

Background Kidney transplant recipients (KTRs) are at high risk for a severe course of coronavirus disease 2019 (COVID-19); thus, effective vaccination is critical. However, the achievement of protective immunogenicity is hampered by immunosuppressive therapies. We assessed cellular and humoral immunity and breakthrough infection rates in KTRs vaccinated with homologous and heterologous COVID-19 vaccination regimens. Method We performed a comparative in-depth analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific T-cell responses using multiplex Fluorospot assays and SARS-CoV-2-specific neutralizing antibodies (NAbs) between three-times homologously (n = 18) and heterologously (n = 8) vaccinated KTRs. Results We detected SARS-CoV-2-reactive T cells in 100% of KTRs upon third vaccination, with comparable frequencies, T-cell expression profiles, and relative interferon γ and interleukin 2 production per single cell between homologously and heterologously vaccinated KTRs. SARS-CoV-2-specific NAb positivity rates were significantly higher in heterologously (87.5%) compared to homologously vaccinated (50.0%) KTRs (P < 0.0001), whereas the magnitudes of NAb titers were comparable between both subcohorts after third vaccination. SARS-CoV-2 breakthrough infections occurred in equal numbers in homologously (38.9%) and heterologously (37.5%) vaccinated KTRs with mild-to-moderate courses of COVID-19. Conclusion Our data support a more comprehensive assessment of not only humoral but also cellular SARS-CoV-2-specific immunity in KTRs to provide an in-depth understanding about the COVID-19 vaccine–induced immune response in a transplant setting.
Fixed Point Free Involutions on the 3-Sphere

In [1], P. A. Smith has proved that the set of fixed points of a periodic homeomorphism T of the 3-sphere S3 onto itself is an i-sphere imbedded in S3, i = -1, 0, 1, or 2, where the -1-sphere denotes the empty set. In trying to prove that an involution (map of period 2) on S3 is conjugate, in the group of all homeomorphisms of S3 onto itself, to an orthogonal involution, it is natural to divide the problem into four cases, as the dimension, n, of the fixed point sphere is -1, 0, 1, or 2, respectively. R. H. Bing, [2], has settled the case n=2 in the negative, unless one assumes that the 2-sphere of fixed points is tamely imbedded. Regarding the case n= 1, Montgomery and Samelson, [3], have shown that, if T is semi-linear, the circle of fixed points cannot be a knotted torus knot of type (p, 2), and moreover, that if the circle of fixed points is not knotted, then the involution, T, is conjugate to an orthogonal involution. This latter result suggests an approach for the case n = -1. An invariant set will mean a set mapped onto itself by the involution. In the absence of fixed points, the invariant circles become important. In fact, we have:
Physiological and life history responses in a mayfly (Callibaetis floridanus) inhabiting ponds with saltwater intrusion

Freshwater salinity varies in natural systems and plays a role in species distribution. Anthropogenic alterations to freshwater salinity regimes include sea level rise and subsequent intrusion of saline waters to inland habitats. While mayflies are generalized to be sensitive to increasing salinity, we still know remarkably little about the physiological processes (and their plasticity) that determine the performance of species in a changing world. Here, we explored life-history outcomes and physiological plasticity in a population of Callibaetis floridanus (Ephemeroptera: Baetidae) from a coastal pond that routinely experiences saltwater intrusion. We reared naiads from egg hatch to adulthood across a gradient of increasing salinities (113, 5,020, 9,921 μS/cm). Radiotracer flux studies (22Na, 35SO4, and 45Ca) were conducted in naiads reared at each salinity, revealing a positive association between ionic concentration and uptake rates. However, the influence of rearing history on ionic influx rates was apparent when naiads were transferred from their respective rearing water to the other experimental conditions. For example, we observed that naiads reared in the low salinity treatment (113 μS/cm) had 10.8-fold higher Na uptake rates than naiads reared at 9,921 μS/cm and transferred to 113 μS/cm. Additionally, naiads acclimated to the higher salinity water exhibited reduced uptake in ion-rich water relative to those reared in more dilute conditions (e.g., in 9,921 μS/cm water, 113 and 5,020 μS/cm acclimated naiads had 1.5- and 1.1-fold higher Na uptake rates than 9,921 μS/cm acclimated naiads, respectively). We found no significant changes in survival (80 ± 4.4%, mean ± s.e.m.) or naiad development time (24 ± 0.3 days, mean ± s.e.m.) across these treatments but did observe a 27% decrease in subimago female body weight in the most dilute condition. This reduction in female weight was associated with higher oxygen consumption rates in naiads relative to the other rearing conditions. Collectively, these data suggests that saline adapted C. floridanus may be more energetically challenged in dilute conditions, which differs from previous observations in other mayfly species.
European dietitians as key agents of the green transition: An exploratory study of their knowledge, attitudes, practices, and training

Introduction How food systems are currently provisioning food to the population is a matter of debate worldwide. Food systems, driven by widespread and increasing adherence to a westernized dietary pattern, are failing to meet people’s basic needs and are draining natural resources. There is a push to make food systems more healthy, fair, and sustainable. To this end, action from all players is needed to meet the international agenda. In this regard, dietitians play a crucial role, as they can provide advice and promote actions that foster the adoption of more sustainable dietary patterns (SDP) as well as the promotion of sustainable food systems. As an emerging requirement in their training, it is crucial to know what dietitians know about SDP as well as their attitudes and current practices in this field in order to strengthen their competences and be key agents for the green transition. For this reason, the aim of the present study is to explore the knowledge, attitudes, practices, and training (KAPT) of European dietitians on SDP by administering an online survey. Methods Cross-sectional survey administered between April-August 2021 to dietitians based in the European countries with National Dietetic Associations or Education Associate Members affiliated to the European Federation of Associations of Dietitians (EFAD). Results were analyzed based on European region of professional practice (Northern/Southern/Western/South-East Europe), area of expertise and years of experience. Results Responses from 2211 dietitians from 25 countries were received, although the analysis was based on those that responded at least 90% of the survey (n=208). European dietitians are lacking training on SDP but are willing to learn more about it. Most dietitians perceive themselves as able to define an SDP, although aspects concerning social and economic sustainability were underestimated. Dietitians concur that barriers exist to the promotion of SDP, such as the lack of updated national food-based dietary guidelines and the absence of support from peers and managers. The country of professional activity seemed to be key to influencing dietitians’ KAPT. Discussion These results emphasize the need to strengthen European dietitians’ training in SDP and increase public/private commitment to consider dietitians as key professionals for the transition towards SDP.
No association of the dopamine D2 receptor genetic bilocus score (rs1800497/rs1799732) on food addiction and food reinforcement in Chilean adults

Purpose: Different systems regulate food intake. In the reward system, dopamine (DA) is the main neurotransmitter, and a variety of genetic variants (rs1799732 and rs1800497) are associated with addiction. Addiction is a highly polygenic disease, where each allelic variant adds a small amount of vulnerability. Polymorphisms rs1799732 and rs1800497 are associated with eating behavior and hedonic hunger, but links to food addiction remain unclear. Aim: To evaluate the association between the bilocus profile (rs1799732-rs1800497) of the dopaminergic pathway with food reinforcement and food addiction in Chilean adults. Methods: A cross-sectional study recruited a convenience sample of 97 obese, 25 overweight, and 99 normal-weight adults (18–35 years). Anthropometric measurements were performed by standard procedures and eating behavior was assessed using the: Food Reinforcement Value Questionnaire (FRVQ) and Yale Food Addiction scale (YFAS). The DRD2 genotypes were determined by TaqMan assays (rs1800497 and rs1799732). A bilocus composite score was calculated. Results: In the normal weight group, individuals who were heterozygous for the rs1977932 variant (G/del) showed higher body weight (p-value 0.01) and abdominal circumference (p-value 0.01) compared to those who were homozygous (G/G). When analyzing rs1800497, a significant difference in BMI was observed for the normal weight group (p-value 0.02) where heterozygous showed higher BMI. In the obese group, homozygous A1/A1 showed higher BMI in comparison to A1/A2 and A2/A2 (p-value 0.03). Also, a significant difference in food reinforcement was observed in the rs1800497, where homozygous for the variant (A1A1) show less reinforcement (p-value 0.01). In relation to the bilocus score in the total sample, 11% showed “very low dopaminergic signaling”, 24.4% were “under”, 49.7% showed “intermediate signaling”, 12.7% showed “high” and 1.4% showed “very high”. No significant genotypic differences were observed in food reinforcement and food addiction by bilocus score. Conclusions: The results indicate that the genetic variants rs1799732 and rs1800497 (Taq1A) were associated with anthropometric measurements but not with food addiction or food reinforcement in Chilean university students. These results suggest that other genotypes, such as rs4680 and rs6277, which affect DA signaling capacity through a multilocus composite score, should be studied. Level V: Evidence obtained from a cross-sectional descriptive study.
Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can develop 4–6 weeks after a school age child becomes infected by SARS-CoV-2. To date, in the United States more than 8,862 cases of MIS-C have been identified and 72 deaths have occurred. This syndrome typically affects children between the ages of 5–13; 57% are Hispanic/Latino/Black/non-Hispanic, 61% of patients are males and 100% have either tested positive for SARS-CoV-2 or had direct contact with someone with COVID-19. Unfortunately, diagnosis of MIS-C is difficult, and delayed diagnosis can lead to cardiogenic shock, intensive care admission, and prolonged hospitalization. There is no validated biomarker for the rapid diagnosis of MIS-C. In this study, we used Grating-coupled Fluorescence Plasmonic (GCFP) microarray technology to develop biomarker signatures in pediatric salvia and serum samples from patients with MIS-C in the United States and Colombia. GCFP measures antibody-antigen interactions at individual regions of interest (ROIs) on a gold-coated diffraction grating sensor chip in a sandwich immunoassay to generate a fluorescent signal based on analyte presence within a sample. Using a microarray printer, we designed a first-generation biosensor chip with the capability of capturing 33 different analytes from 80 μ L of sample (saliva or serum). Here, we show potential biomarker signatures in both saliva and serum samples in six patient cohorts. In saliva samples, we noted occasional analyte outliers on the chip within individual samples and were able to compare those samples to 16S RNA microbiome data. These comparisons indicate differences in relative abundance of oral pathogens within those patients. Microsphere Immunoassay (MIA) of immunoglobulin isotypes was also performed on serum samples and revealed MIS-C patients had several COVID antigen-specific immunoglobulins that were significantly higher than other cohorts, thus identifying potential new targets for the second-generation biosensor chip. MIA also identified additional biomarkers for our second-generation chip, verified biomarker signatures generated on the first-generation chip, and aided in second-generation chip optimization. Interestingly, MIS-C samples from the United States had a more diverse and robust signature than the Colombian samples, which was also illustrated in the MIA cytokine data. These observations identify new MIS-C biomarkers and biomarker signatures for each of the cohorts. Ultimately, these tools may represent a potential diagnostic tool for use in the rapid identification of MIS-C.