Reconstruction of 1,000 Projection Neurons Reveals New Cell Types and Organization of Long-Range Connectivity in the Mouse Brain.

Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons constitute more than 85 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

Inhibition of the mPTP and Lipid Peroxidation Is Additively Protective Against I/R Injury.

BACKGROUND: During myocardial ischemia/reperfusion (I/R) injury, high levels of matrix Ca2+ and reactive oxygen species (ROS) induce the opening of the mitochondrial permeability transition pore (mPTP), which causes mitochondrial dysfunction and ultimately necrotic death. However, the mechanisms of how these triggers individually or cooperatively open the pore have yet to be determined. METHODS: Here, we use a combination of isolated mitochondrial assays and in vivo I/R surgery in mice. We challenged isolated liver and heart mitochondria with Ca2+, ROS, and Fe2+ to induce mitochondrial swelling. Using inhibitors of the mPTP (cyclosporine A or ADP) lipid peroxidation (ferrostatin-1, MitoQ), we determined how the triggers elicit mitochondrial damage. Additionally, we used the combination of inhibitors during I/R injury in mice to determine if dual inhibition of these pathways is additivity protective. RESULTS: In the absence of Ca2+, we determined that ROS fails to trigger mPTP opening. Instead, high levels of ROS induce mitochondrial dysfunction and rupture independently of the mPTP through lipid peroxidation. As expected, Ca2+ in the absence of ROS induces mPTP-dependent mitochondrial swelling. Subtoxic levels of ROS and Ca2+ synergize to induce mPTP opening. Furthermore, this synergistic form of Ca2+- and ROS-induced mPTP opening persists in the absence of CypD (cyclophilin D), suggesting the existence of a CypD-independent mechanism for ROS sensitization of the mPTP. These ex vivo findings suggest that mitochondrial dysfunction may be achieved by multiple means during I/R injury. We determined that dual inhibition of the mPTP and lipid peroxidation is significantly more protective against I/R injury than individually targeting either pathway alone. CONCLUSIONS: In the present study, we have investigated the relationship between Ca2+ and ROS, and how they individually or synergistically induce mitochondrial swelling. Our findings suggest that Ca2+ mediates mitochondrial damage through the opening of the mPTP, although ROS mediates its damaging effects through lipid peroxidation. However, subtoxic levels both Ca2+ and ROS can induce mPTP-mediated mitochondrial damage. Targeting both of these triggers to preserve mitochondria viability unveils a highly effective therapeutic approach for mitigating I/R injury.

A pragmatic randomized trial of mailed fecal immunochemical testing to increase colorectal cancer screening among low-income and minoritized populations.

BACKGROUND: Colorectal cancer (CRC) screening is underused, particularly among low-income and minoritized populations, for whom the coronavirus disease 2019 (COVID-19) pandemic has challenged progress in achieving equity. METHODS: A hub-and-spoke model was used. The hub was a nonacademic organization and the spokes were three community health center (CHC) systems overseeing numerous clinic sites. Via a cluster-randomized trial design, nine clinic sites were randomized to intervention and 16 clinic sites were randomized to usual care. Patient-level interventions included invitation letters, mailed fecal immunochemical tests (FITs), and call/text-based reminders. Year 1 intervention impact, which took place during the COVID-19 pandemic, was assessed as the proportion completing screening among individuals not up to date at baseline, which compared intervention and nonintervention clinics accounting for intraclinic cluster variation; confidence intervals (CIs) around differences not including 0 were interpreted as statistically significant. RESULTS: Among 26,736 patients who met eligibility criteria, approximately 58% were female, 55% were Hispanic individuals, and 44% were Spanish speaking. The proportion completing screening was 11.5 percentage points (ppts) (95% CI, 6.1-16.9 ppts) higher in intervention versus usual care clinics. Variation in differences between intervention and usual care clinics was observed by sex (12.6 ppts [95% CI, 7.2-18.0 ppts] for females; 8.8 ppts [95% CI, 4.7-13.9 ppts] for males) and by racial and ethnic group (13.8 ppts [95% CI, 7.0-20.6 ppts] for Hispanic individuals; 13.0 ppts [95% CI, 3.6-22.4 ppts] for Asian individuals; 11.3 ppts [95% CI, 5.8-16.8 ppts] for non-Hispanic White individuals; 6.1 ppts [95% CI, 0.8-10.4 ppts] for Black individuals). CONCLUSIONS: A regional mailed FIT intervention was effective for increasing CRC screening rates across CHC systems serving diverse, low-income populations.

Patients' Perspectives on Health-Related Social Needs and Recommendations for Interventions: A Qualitative Study.

RATIONALE & OBJECTIVE: People with low socioeconomic status are disproportionately affected by kidney failure, and their adverse outcomes may stem from unmet health-related social needs. This study explored hemodialysis patient perspectives on health-related social needs and recommendations for intervention. STUDY DESIGN: Qualitative study using semistructured interviews. SETTINGS & PARTICIPANTS: Thirty-two people with low socioeconomic status receiving hemodialysis at 3 hemodialysis facilities in Austin, Texas. ANALYTICAL APPROACH: Interviews were analyzed for themes and subthemes using the constant comparative method. RESULTS: Seven themes and 21 subthemes (in parentheses) were identified: (1) kidney failure was unexpected (never thought it would happen to me; do not understand dialysis); (2) providers fail patients (doctors did not act; doctors do not care); (3) dialysis is detrimental (life is not the same; dialysis is all you do; dialysis causes emotional distress; dialysis makes you feel sick); (4) powerlessness (dependent on others; cannot do anything about my situation); (5) financial resource strain (dialysis makes you poor and keeps you poor; disability checks are not enough; food programs exist but are inconsistent; eat whatever food is available; not enough affordable housing; unstable housing affects health and well-being); (6) motivation to keep going (faith, support system, will to live); and (7) interventions should promote self-efficacy (navigation of community resources, support groups). LIMITATIONS: Limited quantitative data such as on dialysis vintage, and limited geographic representation. CONCLUSIONS: Dialysis exacerbates financial resource strain, and health-related social needs exacerbate dialysis-related stress. The participants made recommendations to address social needs with an emphasis on increasing support and community resources for this population. PLAIN-LANGUAGE SUMMARY: People receiving dialysis often experience health-related social needs, such as food and housing needs, but little is known about how these impact patients' health and well-being or how to best address them. We interviewed people receiving dialysis about how health-related social needs affect them and what they think dialysis facilities can do to help them address those needs. The participants reported that they often lose their independence after starting dialysis and health-related social needs are common, exacerbate their stress and emotional distress, and reduce their sense of well-being. Dialysis facilities may be able to enhance the experience of these patients by facilitating connections with local resources and providing opportunities for patients to support one another.

Clinical characteristics and outcomes of aortic prosthetic valve endocarditis: comparison between transcatheter and surgical bioprostheses.

PURPOSE: Most data regarding infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) comes from TAVI registries, rather than IE dedicated cohorts. The objective of our study was to compare the clinical and microbiological profile, imaging features and outcomes of patients with IE after SAVR with a biological prosthetic valve (IE-SAVR) and IE after TAVI (IE-TAVI) from 6 centres with an Endocarditis Team (ET) and broad experience in IE. METHODS: Retrospective analysis of prospectively collected data. From the time of first TAVI implantation in each centre to March 2021, all consecutive patients admitted for IE-SAVR or IE-TAVI were prospectively enrolled. Follow-up was monitored during admission and at 12 months after discharge. RESULTS: 169 patients with IE-SAVR and 41 with IE-TAVI were analysed. Early episodes were more frequent among IE-TAVI. Clinical course during hospitalization was similar in both groups, except for a higher incidence of atrioventricular block in IE-SAVR. The most frequently causative microorganisms were S. epidermidis, Enterococcus spp. and S. aureus in both groups. Periannular complications were more frequent in IE-SAVR. Cardiac surgery was performed in 53.6% of IE-SAVR and 7.3% of IE-TAVI (p=0.001), despite up to 54.8% of IE-TAVI patients had an indication. No differences were observed about death during hospitalization (32.7% vs 35.0%), and at 1-year follow-up (41.8% vs 37.5%), regardless of whether the patient underwent surgery or not. CONCLUSION: Patients with IE-TAVI had a higher incidence of early prosthetic valve IE. Compared to IE-SAVR, IE-TAVI patients underwent cardiac surgery much less frequently, despite having surgical indications. However, in-hospital and 1-year mortality rate was similar between both groups.

Interfacial host-guest complexation for inverted perovskite solar cells.

Perovskite solar cells have demonstrated exceptional development over the past decade, but their stability remains a challenge toward the application of this technology. Several strategies have been used to address this, and the use of host-guest complexation has recently attracted more interest. However, this approach has primarily been exploited in conventional perovskite solar cells based on n-i-p architectures, while its use in inverted p-i-n devices remains unexplored. Herein, we employ representative crown ether, dibenzo-24-crown-8, for interfacial host-guest complexation in inverted perovskite solar cells based on methylammonium and methylammonium-free formamidinium-cesium halide perovskite compositions. Upon post-treatment of the perovskite films, we observed nanostructures on the surface that were associated with the reduced amount of trap states at the interface with the electron transport layer. As a result, we demonstrate improved efficiencies and operational stabilities following ISOS-D-2I and ISOS-L-2I protocols, demonstrating the viability of this approach to advance device stability.

Antioxidant Enzymes and Their Potential Use in Breast Cancer Treatment.

According to the World Health Organization (WHO), breast cancer (BC) is the deadliest and the most common type of cancer worldwide in women. Several factors associated with BC exert their effects by modulating the state of stress. They can induce genetic mutations or alterations in cell growth, encouraging neoplastic development and the production of reactive oxygen species (ROS). ROS are able to activate many signal transduction pathways, producing an inflammatory environment that leads to the suppression of programmed cell death and the promotion of tumor proliferation, angiogenesis, and metastasis; these effects promote the development and progression of malignant neoplasms. However, cells have both non-enzymatic and enzymatic antioxidant systems that protect them by neutralizing the harmful effects of ROS. In this sense, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), thioredoxin reductase (TrxR), and peroxiredoxin (Prx) protect the body from diseases caused by oxidative damage. In this review, we will discuss mechanisms through which some enzymatic antioxidants inhibit or promote carcinogenesis, as well as the new therapeutic proposals developed to complement traditional treatments.

The rs1477196 SNP of the FTO Gene is Associated with Primary Knee Osteoarthritis in a Female Population from Northern Mexico.

Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.

Target protein deglycosylation in living cells by a nanobody-fused split O-GlcNAcase.

O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification that is presented on thousands of nucleocytoplasmic proteins. Interrogating the role of O-GlcNAc on a single target protein is crucial, yet challenging to perform in cells. Herein, we developed a nanobody-fused split O-GlcNAcase (OGA) as an O-GlcNAc eraser for selective deglycosylation of a target protein in cells. After systematic cellular optimization, we identified a split OGA with reduced inherent deglycosidase activity that selectively removed O-GlcNAc from the desired target protein when directed by a nanobody. We demonstrate the generality of the nanobody-fused split OGA using four nanobodies against five target proteins and use the system to study the impact of O-GlcNAc on the transcription factors c-Jun and c-Fos. The nanobody-directed O-GlcNAc eraser provides a new strategy for the functional evaluation and engineering of O-GlcNAc via the selective removal of O-GlcNAc from individual proteins directly in cells.

Palliative care utilization across health sectors for patients with gynecologic malignancies in Ontario, Canada from 2006 to 2018.

OBJECTIVE: Early palliative care (PC) is associated with improved patient quality of life, less aggressive end-of-life care, and prolonged survival. We evaluated patterns of PC delivery in gynecologic oncology. METHODS: We conducted a population-based, retrospective cohort study of gynecologic cancer decedents in Ontario from 2006 to 2018 using linked administrative health care data. RESULTS: The cohort included 16,237 decedents; 51.1% died of ovarian cancer, 30.3% uterine cancer, 12.1% cervical cancer, and 6.5% vulvar/vaginal cancers. Palliative care was most often delivered in the hospital inpatient setting in 81%, and 53% received specialist PC. PC was first received during hospital admission in 53%, and by outpatient physician care in only 23%. Palliative care was initiated a median 193 days prior to death, with the lowest two quintiles initiating care ≤70 days before death. The average user of PC resources (third quintile) received 68 days of PC. While cumulative use of community PC gradually increased over the final year of life, institutional palliative care use exponentially rose from 12 weeks until death. On multivariable analyses, predictors of initiating palliative care during a hospital admission included age ≥70 years at death, ≤3 month cancer survival, having cervical or uterine cancer, not having a primary care provider, or being in the lowest 3 income quintiles. CONCLUSION: Most palliative care is initiated and delivered during hospital admission, and is initiated late in a significant proportion. Strategies to increase access to anticipatory and integrated palliative care may improve the quality of the disease course and the end of life.

Seeking utopia: Psychologies' waves toward decoloniality.

This paper provides a review of empirical studies published with a decolonial epistemic approach in psychology. Our goal was to better understand how decolonial approaches are being practiced empirically in psychology, with an emphasis on community-social psychology. We first discuss the context of colonization and coloniality in the research process as orienting information. We identified 17 peer-reviewed empirical articles with a decolonial approach to psychology scholarship and discerned four waves that characterize the articles: relationally-based research to transgress fixed hierarchies and unsettle power, research from the heart, sociohistorical intersectional consciousness, and desire-based future-oriented research to rehumanize and seek utopia. Community-social psychology research with a decolonial approach has the potential to remember grassroots efforts, decolonizing our world.

Patient-derived xenografts and in vitro model show rationale for imatinib mesylate repurposing in HEY1-NCoA2-driven mesenchymal chondrosarcoma.

Mesenchymal chondrosarcoma (MCS) is a high-grade malignancy that represents 2-9% of chondrosarcomas and mostly affects children and young adults. HEY1-NCoA2 gene fusion is considered to be a driver of tumorigenesis and it has been identified in 80% of MCS tumors. The shortage of MCS samples and biological models creates a challenge for the development of effective therapeutic strategies to improve the low survival rate of MCS patients. Previous molecular studies using immunohistochemical staining of patient samples suggest that activation of PDGFR signaling could be involved in MCS tumorigenesis. This work presents the development of two independent in vitro and in vivo models of HEY1-NCoA2-driven MCS and their application in a drug repurposing strategy. The in vitro model was characterized by RNA sequencing at the single-cell level and successfully recapitulated relevant MCS features. Imatinib, as well as specific inhibitors of ABL and PDGFR, demonstrated a highly selective cytotoxic effect targeting the HEY1-NCoA2 fusion-driven cellular model. In addition, patient-derived xenograft (PDX) models of MCS harboring the HEY1-NCoA2 fusion were developed from a primary tumor and its distant metastasis. In concordance with in vitro observations, imatinib was able to significantly reduce tumor growth in MCS-PDX models. The conclusions of this study serve as preclinical results to revisit the clinical efficacy of imatinib in the treatment of HEY1-NCoA2-driven MCS.

Large-scale provocation studies identify maladaptive responses to ubiquitous aeroallergens as a correlate of severe allergic rhinoconjunctivitis and asthma.

BACKGROUND: Allergic asthma (AA) and allergic rhinoconjunctivitis (ARC) are common comorbid environmentally triggered diseases. We hypothesized that severe AA/ARC reflects a maladaptive or unrestrained response to ubiquitous aeroallergens. METHODS: We performed provocation studies wherein six separate cohorts of persons (total n = 217) with ARC, with or without AA, were challenged once or more with fixed concentrations of seasonal or perennial aeroallergens in an aeroallergen challenge chamber (ACC). RESULTS: Aeroallergen challenges elicited fully or partially restrained vs. unrestrained evoked symptom responsiveness, corresponding to the resilient and adaptive vs. maladaptive AA/ARC phenotypes, respectively. The maladaptive phenotype was evoked more commonly during challenge with a non-endemic versus endemic seasonal aeroallergen. In an AA cohort, symptom responses evoked after house dust mite (HDM) challenges vs. recorded in the natural environment were more accurate and precise predictors of asthma severity and control, lung function (FEV1), and mechanistic correlates of maladaptation. Correlates included elevated levels of peripheral blood CD4+ and CD8+ T-cells, eosinophils, and T-cell activation, as well as gene expression proxies for ineffectual epithelial injury/repair responses. Evoked symptom severity after HDM challenge appeared to be more closely related to levels of CD4+ and CD8+ T-cells than eosinophils, neutrophils, or HDM-specific IgE. CONCLUSIONS: Provocation studies support the concept that resilience, adaptation, and maladaptation to environmental disease triggers calibrate AA/ARC severity. Despite the ubiquity of aeroallergens, in response to these disease triggers in controlled settings (ie, ACC), most atopic persons manifest the resilient or adaptive phenotype. Thus, ARC/AA disease progression may reflect the failure to preserve the resilient or adaptive phenotype. The triangulation of CD8+ T-cell activation, airway epithelial injury/repair processes and maladaptation in mediating AA disease severity needs more investigation.

Photophysical and Photoelectrochemical Properties of CsPbBr3 Films Grown by Electrochemically Assisted Deposition.

Perovskite have had a great impact on the solid-state physics world in the last decade not only achieving great success in photovoltaics but, more recently, also in the implementation of other optoelectronic devices. One of the main obstacles for the adoption of Pb-based perovskite technologies are the high amounts of Pb needed in the conventional preparation methods. Here we present for the first time a detailed analysis of the photophysical and photoelectrochemical properties of CsPbBr3 films directly grown on fluorine-doped tin oxide (FTO) coated glass through a novel technique based in the electrodeposition of PbO2 as CsPbBr3 precursor. This technique allows to save up to 90 % of the Pb used compared to traditional methods and can be scalable compared with the commonly used spin-coating process. The low temperature analysis of their photoluminescence spectra, performed in both steady state and time dependence, revealed a strong interaction between electrons and longitudinal optical (LO) phonons dominant at high temperatures. On the other hand, the electrochemical and photoelectrochemical analysis proves that CsPbBr3 prepared using this new method has state-of-the-art features, showing a p-type behavior under depletion regime. This is also confirmed by photoelectrochemical measurements using p-benzoquinone as target molecule. These results prove that the proposed method can be used to produce excellent CsPbBr3 films, saving much of the lead waste.

Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases.

BACKGROUND: Signifying the 2-compartments/1-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (eg, house dust mites [HDMs]). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resilience or adaptation. OBJECTIVE: We sought to determine whether ARC/AA severity relates to maladaptive responses to disease triggers. METHODS: Adults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber. Mechanistic traits associated with disease severity were identified. RESULTS: HDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity associated with CD8+ T cells, whereas airway inflammation associated with both CD8+ T cells and eosinophils. Hallmark peripheral blood maladaptive traits were increased natural killer and CD8+ T cells, lower CD4+ mucosal-associated invariant T cells, and deficiencies along the TLR-IRF-IFN antiviral pathway. Maladaptive traits tracking HDM-associated ARC also contributed to AA risk and severity models. CONCLUSIONS: Repetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.

Integration of Maps Enables a Cytogenomics Analysis of the Complete Karyotype in Solea senegalensis.

The Pleuronectiformes order, which includes several commercially-important species, has undergone extensive chromosome evolution. One of these species is Solea senegalensis, a flatfish with 2n = 42 chromosomes. In this study, a cytogenomics approach and integration with previous maps was applied to characterize the karyotype of the species. Synteny analysis of S. senegalensis was carried out using two flatfish as a reference: Cynoglossus semilaevis and Scophthalmus maximus. Most S. senegalensis chromosomes (or chromosome arms for metacentrics and submetacentrics) showed a one-to-one macrosyntenic pattern with the other two species. In addition, we studied how repetitive sequences could have played a role in the evolution of S. senegalensis bi-armed (3, and 5-9) and acrocentric (11, 12 and 16) chromosomes, which showed the highest rearrangements compared with the reference species. A higher abundance of TEs (Transposable Elements) and other repeated elements was observed adjacent to telomeric regions on chromosomes 3, 7, 9 and 16. However, on chromosome 11, a greater abundance of DNA transposons was detected in interstitial BACs. This chromosome is syntenic with several chromosomes of the other two flatfish species, suggesting rearrangements during its evolution. A similar situation was also found on chromosome 16 (for microsatellites and low complexity sequences), but not for TEs (retroelements and DNA transposons). These differences in the distribution and abundance of repetitive elements in chromosomes that have undergone remodeling processes during the course of evolution also suggest a possible role for simple repeat sequences in rearranged regions.

Acid spill impact on Sonora River basin. Part I. sediments: Affected area, pollutant geochemistry and health aspects.

The Sonora River and its tributary streams (Tinajas, Bacanuchi) were impacted in 2014 by an acid solution spill (approximately 40,000 m3). This study aims to presents a clear and supported overview to determining the spill's consequences on the environment and the people inhabiting the area. The elements quantified were those found in the spilled solution: Al, As, Cu, Fe, Mn, Pb, and Zn. Potential Toxic Element (PTE) concentration means from 187 sediment samples were, in mg.kg-1: Al = 7,307, As = 16.6, Ba = 128 Cu = 106 Fe = 15,764, Mn = 566, Pb = 46 and Zn = 99. Differences between PTE concentrations in the most impacted sediments and those of the local baseline, sampled in streams not affected by the spill and regional baseline values, were not statistically significant. The similarity of PTE concentrations among sediments may be explained by natural geological enrichment, historical mining impacts, and a low increase of PTE in sediments after the acid spill because of natural and anthropogenic attenuation. Mainly heavy rains, natural pedogenic carbonates, and remedial work done by the mining company (retaining dam, adding lime; precipitation, collecting formed solids, and transport to the mine). The Contamination Factor (C.F.), Enrichment Factor (E.F.), and Geo-accumulation Index (Igeo) were determined. The C.F. indicated low and moderate contamination in all elements. Cu exhibited the highest E.F., from moderate to significant enrichment. The Igeo generally ranged from -0.02 to 0.15. Cu and Zn were classified as moderately to heavily contaminated. In local baseline sediments, the Cu C.F. varied from moderate to very high contamination, the Cu E.F. from moderate to significant enrichment, while the As, and Pb Igeo ranged from uncontaminated to moderately contaminated. In general, normalization demonstrated a high degree of Cu enrichment at sites 1-14. Sequential extractions indicated that only Cu was found in all fractions, including a significant exchangeable fraction in the very impacted sediments (1-14). The other PTEs were distributed between the Fe/Mn oxide fraction and the residual phase. Principal Components Analysis for PTE concentrations indicated three different groups with similar geochemical patterns and allowing to identify the PTE potentially sources: the first sediments from sites 1-14 were the impacted sediments in accordance with pH and electrical conductivity results, the second group from sites 15-20 showed characteristics of the mineralized environment, and the third from sites 21-30 were unrelated to the spillage. The area impacted by the acid solution spill reached approximately 30 km downstream, just roughly 15% of the initially considered area.

Effects of landscape characteristics, anthropogenic factors, and seasonality on water quality in Portland, Oregon.

Urban areas often struggle with deteriorated water quality because of complex interactions between landscape factors and climatic variables. However, few studies have considered the effects of landscape variables on water quality at a sub-500-m scale. We conducted a spatial statistical analysis of six pollutants for 128 water quality stations in four watersheds around Portland, Oregon, using data from 2015 to 2021 for the wet season at two microscales (100 m and 250 m buffers). E. coli was associated with land cover, soil type, topography, and pipe length, while lead variations were best explained by topographic variables. Developed land cover and impervious surface explained variations in nitrate, while orthophosphate was associated with mean elevation. Models for zinc included land cover and topographic variables in addition to pipe length. Spatial regression models better explain variations in water quality than ordinary least squares models, indicating strong spatial autocorrelation for some variables. Our findings provide valuable insights to city planners and researchers seeking to improve water quality in metropolitan areas by manipulating city landscapes.

Impact of the droplet size of canola oil-in-water emulsions on the rheology and sensory acceptability of reduced-milk fat stirred yogurt.

A coarse canola oil-in-water (O/W) emulsion (dispersed mass fraction 0.1) was prepared by adding oil to whey protein hydrolysate (WPH)-citric pectin (CP) soluble complex (1% total biopolymer weight; WPH to CP mass ratio 6:1; pH 4.25) aqueous phase using a high shear homogenizer (4000 rpm, 2 min). The coarse O/W emulsion was further homogenized to obtain emulsions (Ex) with different mean droplet sizes (4000, 3000, 120 and 60 nm). A full-fat yogurt (YC; 26 ± 0.3 g milk fat L-1) was prepared from reconstituted whole milk powder (WMP, 3% milk fat) and skim milk powder (SMP, 0.01% milk fat). Reduced-milk fat yogurt (YEx 13 ± 0.3 g milk fat L-1) variations were prepared from WMP + SMP + Ex, where Ex substituted 50% of the milk-fat contained in YC. The viscosity and viscoelastic moduli were lower for YEx than for YC; the effect was more pronounced for E60 and E120. Aroma was non-significantly different between YC and YEx. A multivariate analysis showed that YEx overall acceptability was linked to taste and after taste attributes and to the viscosity perceived in mouth. The loss modulus showed anti-correlation directionality with the overall acceptance. The smaller mean droplet sized YEx exhibited the highest overall acceptability. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05573-3.

Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.

PURPOSE: Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo. METHODS: Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic in KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish. RESULTS: We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressive neurological and neurosensory abnormalities, and variable white matter involvement. We describe novel KARS1-associated signs such as autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement. Loss of kars1 leads to upregulation of p53, tissue-specific apoptosis, and downregulation of neurodevelopmental related genes, recapitulating key tissue-specific disease phenotypes of patients. Inhibition of p53 rescued several defects of kars1-/- knockouts. CONCLUSION: Our work delineates the clinical spectrum associated with KARS1 defects and provides a novel animal model for KARS1-related human diseases revealing p53 signaling components as potential therapeutic targets.