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1.
J Chem Phys ; 160(18)2024 May 14.
Article in English | MEDLINE | ID: mdl-38721903

ABSTRACT

We present a technique for measuring the interactions between pairs of colloidal particles in two optical traps. This method is particularly suitable for measuring strongly attractive potentials, an otherwise challenging task. The interaction energy is calculated from the distribution of inter-particle separations by accounting for the contribution from the optical traps with arbitrary trap profiles. The method is simple to implement and applicable to different types of pair potentials and optical trapping geometries. We apply the method to measure dipolar pair interactions in experiments with paramagnetic colloids in external magnetic fields. We obtain consistent and accurate results in all regimes, from strongly attractive to repulsive potentials. By means of computer simulations, we demonstrate that the proposed method can be successfully applied to systems with complex pair interactions characterized by multiple attractive and repulsive regimes, which are ubiquitous in soft and biological matter.

2.
Hosp Pediatr ; 14(5): 348-355, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38572566

ABSTRACT

OBJECTIVE: To determine if electronic medical record (EMR) changes and implementation of a study on firearm storage practices changed identification of firearm exposure in children presenting to a pediatric emergency department (PED) with mental health complaints. We also sought to determine the accuracy of information collected on firearm storage practices. METHODS: Retrospective study of EMR documentation of firearm exposure in PED patients with mental health complaints from January 20, 2015 until November 20, 2017. EMR changes occurred on January 20, 2016 and the firearms study began on February 13, 2016. The primary outcome was documentation of firearm exposure. Secondary outcomes were documentation of unsafe firearm storage practices. We also examined differences between clinical and research documentation of unsafe firearm storage practices post-intervention. We compared groups using descriptive statistics and chi-squared tests. We used statistical process control to examine the relationship between interventions and changes in outcomes. RESULTS: 5582 encounters were examined. Identification of firearm exposure increased from 11 to 17% postintervention. Identification of unsafe storage practices increased from 1.9% to 4.4% across all encounters. Special cause variation in both metrics occurred concurrently with the interventions. Postintervention, unsafe firearms storage practices in firearm owning families were under-identified (39% identified as not triple-safe in clinical data vs 75% in research data). CONCLUSIONS: EMR changes and implementation of a firearms study improved identification of firearm exposure and unsafe storage practices in families of PED patients being evaluated for mental health complaints. However, unsafe storage practices continued to be under-identified in firearm-owning families.


Subject(s)
Emergency Service, Hospital , Firearms , Humans , Retrospective Studies , Child , Male , Female , Emergency Service, Hospital/statistics & numerical data , Electronic Health Records , Adolescent , Mental Disorders/diagnosis
3.
Viruses ; 16(4)2024 04 07.
Article in English | MEDLINE | ID: mdl-38675911

ABSTRACT

Zika virus (ZIKV) remains a public health concern, with epidemics in endemic regions and sporadic outbreaks in new areas posing significant threats. Several mosquito-borne flaviviruses that can cause human illness, including West Nile, Usutu, and St. Louis encephalitis, have associations with birds. However, the susceptibility of chickens to ZIKV and their role in viral epidemiology is not currently known. We investigated the susceptibility of chickens to experimental ZIKV infection using chickens ranging from 1-day-old chicks to 6-week-old birds. ZIKV caused no clinical signs in chickens of all age groups tested. Viral RNA was detected in the blood and tissues during the first 5 days post-inoculation in 1-day and 4-day-old chicks inoculated with a high viral dose, but ZIKV was undetectable in 6-week-old birds at all timepoints. Minimal antibody responses were observed in 6-week-old birds, and while present in younger chicks, they waned by 28 days post-infection. Innate immune responses varied significantly between age groups. Robust type I interferon and inflammasome responses were measured in older chickens, while limited innate immune activation was observed in younger chicks. Signal transducer and activator of transcription 2 (STAT2) is a major driver of host restriction to ZIKV, and chicken STAT2 is distinct from human STAT2, potentially contributing to the observed resistance to ZIKV infection. The rapid clearance of the virus in older chickens coincided with an effective innate immune response, highlighting age-dependent susceptibility. Our study indicates that chickens are not susceptible to productive ZIKV infection and are unlikely to play a role in the ZIKV epidemiology.


Subject(s)
Chickens , Immunity, Innate , Poultry Diseases , Zika Virus Infection , Zika Virus , Animals , Chickens/virology , Zika Virus Infection/immunology , Zika Virus Infection/virology , Zika Virus/immunology , Disease Susceptibility , Poultry Diseases/virology , Poultry Diseases/immunology , Age Factors , Antibodies, Viral/blood , RNA, Viral/genetics
4.
J Endocrinol Invest ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38436903

ABSTRACT

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, and for this reason, all guidelines for CV risk management provide the same targets in controlling traditional CV risk factors in patients with type 1 or type 2 diabetes at equal CV risk class. Aim of our study was to evaluate and compare CV risk management in patients with type 1 and type 2 diabetes included in AMD Annals Database paying particular attention to indicators of clinical inertia. METHODS: This was a multicenter, observational, retrospective study of AMD Annals Database during year 2022. Patients with diabetes were stratified on the basis of their cardiovascular risk, according to ESC-EASD guidelines. The proportion of patients not treated with lipid-lowering despite LDL cholesterol > to 100 mg/dl or the proportion of patients not treated with antihypertensive drug despite BP > 140/90 mmhg and proportion of patients with proteinuria not treated with angiotensin converting enzyme inhibitors or angiotensinogen receptor blockers (ACE/ARBs) were considered indicators of clinical inertia. The proportion of patients reaching at the same time HbA1c < 7% LDL < 70 mg/dl and BP < 130/80 mmhg were considered to have good multifactorial control. Overall quality of health care was evaluated by the Q-score. RESULTS: Using the inclusion criteria and stratifying patients by ESC/EASD Cardiovascular Risk categories, we included in the analysis 118.442 patients at High Cardiovascular risk and 416.246 patients at Very High Cardiovascular risk. The proportion of patients with good multifactorial risk factor control was extremely low in both T1D and T2D patients in each risk class. At equal risk class, the patients with T1D had lower proportion of subjects reaching HbA1c, LDL, or Blood Pressure targets. Indicators of clinical inertia were significantly higher compared with patients with T2D at equal risk class. Data regarding patients with albuminuria not treated with RAAS inhibitors were available only for those at Very High risk and showed that the proportion of patients not treated was again significantly higher in patients with T1DM. CONCLUSIONS: In conclusion, this study provides evidence of wide undertreatment of traditional cardiovascular risk factors among patients with diabetes included in AMD Annals Database. Undertreatment seems to be more pronounced in individuals with T1D compared to those with T2D and is frequently due to clinical inertia.

5.
Lab Chip ; 24(6): 1685-1701, 2024 03 12.
Article in English | MEDLINE | ID: mdl-38317604

ABSTRACT

Geometry and mechanical characteristics of the environment surrounding the Engineered Heart Tissues (EHT) affect their structure and function. Here, we employed a 3D tissue culture platform fabricated using two-photon direct laser writing with a high degree of accuracy to control parameters that are relevant to EHT maturation. Using this platform, we first explore the effects of geometry based on two distinct shapes: a rectangular seeding well with two attachment sites, and a stadium-like seeding well with six attachment sites that are placed symmetrically along hemicylindrical membranes. The former geometry promotes uniaxial contraction of the tissues; the latter additionally induces diagonal fiber alignment. We systematically increase the length of the seeding wells for both configurations and observe a positive correlation between fiber alignment at the center of the EHTs and tissue length. With increasing length, an undesirable thinning and "necking" also emerge, leading to the failure of longer tissues over time. In the second step, we optimize the stiffness of the seeding wells and modify some of the attachment sites of the platform and the seeding parameters to achieve tissue stability for each length and geometry. Furthermore, we use the platform for electrical pacing and calcium imaging to evaluate the functional dynamics of EHTs as a function of frequency.


Subject(s)
Myocytes, Cardiac , Tissue Engineering , Tissue Engineering/methods , Lasers , Myocardial Contraction
8.
Equine Vet J ; 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38301732

ABSTRACT

BACKGROUND: Equine grass sickness (EGS) is a frequently fatal multisystem neuropathy of equids. The aetiology is unknown; proposed causes include toxicoinfection with Clostridium botulinum and a mycotoxicosis. The effect of EGS on the organisation and structural integrity of the skeletal neuromuscular junction (NMJ), the target of botulinum neurotoxins (BoNTs), is unknown. OBJECTIVES: To compare the organisation and structural integrity of skeletal NMJs from EGS horses, control horses and one horse with a presumptive diagnosis of botulism. STUDY DESIGN: Blinded, retrospective case control. METHODS: NMJs in samples of diaphragm or intercostal muscle from six EGS horses, three control horses and one equine botulism case were compared using electron microscopy, morphometry and confocal light microscopy. RESULTS: A significantly higher percentage of EGS NMJs had abnormal morphology (EGS 72.2%, 95% CI 55.6-84.4; Controls 6.9%, 1.7-23.8; OR 35.1, 8.47-244.8; p < 0.001). EGS NMJs had a significantly lower mean volume fraction occupied by synaptic vesicles (SVs) (EGS 18.7%, 12.6-28.0; Controls 36.3%, 20.8-63.4; p = 0.024). EGS NMJs had evidence of accelerated SV exocytosis and SV depletion, accumulation of neurofilament-like material in terminal boutons and/or bouton degeneration. NMJs from the botulism horse had dense packing of SVs towards the presynaptic membrane active zone, consistent with BoNT intoxication, but had absence of the abnormalities identified in EGS NMJs. MAIN LIMITATIONS: Group sizes were limited by difficulties obtaining suitably processed samples. Ages of control and EGS horses differed. Botulism was diagnosed based on clinical and post mortem findings. CONCLUSIONS: EGS is associated with major changes in skeletal NMJ ultrastructure that are inconsistent with the effects of BoNTs. SV depletion may reflect increased exocytosis coupled with reduced repopulation of SVs via anterograde axonal transport and endocytosis, consistent with the action of an excitatory presynaptic toxin and/or neurotransmitter reuptake inhibitor. Skeletal NMJs represent a previously unrecognised target for the toxin that causes EGS.

9.
HIV Med ; 25(4): 424-439, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38092529

ABSTRACT

INTRODUCTION: Advancements in and accessibility to effective antiretroviral therapy has improved the life expectancy of people living with HIV, increasing the proportion of people living with HIV reaching older age (≥60 years), making this population's health-related quality of life (HRQoL) more relevant. Our aim was to identify the determinants of poor HRQoL in people living with HIV aged ≥60 years and compare them with those of their younger counterparts. METHODS: We used data from the 'Vive+' study, a cross-sectional survey conducted between October 2019 and March 2020, nested within the PISCIS cohort of people living with HIV in Catalonia and the Balearic Islands, Spain. We used the 12-item short-form survey (SF-12), divided into a physical component summary (PCS) and a mental component summary (MCS), to evaluate HRQoL. We used the least absolute shrinkage and selection operator for variable selection and used multivariable regression models to identify predictors. RESULTS: Of the 1060 people living with HIV (78.6% males) who participated in the study, 209 (19.7%) were aged ≥60 years. When comparing older people living with HIV (≥60 years) and their younger counterparts, older people exhibited a worse PCS (median 51.3 [interquartile range {IQR} 46.0-58.1] vs. 46.43 [IQR 42.5-52.7], p < 0.001) but a similar MCS (median 56.0 [IQR 49.34-64.7] vs. 57.0 [IQR 48.9-66.3], p = 0.476). In the multivariable analysis, cognitive function correlated with a PCS (ß correlation factor [ß] -0.18, p = 0.014), and depressive symptoms and satisfaction with social role correlated with an MCS (ß 0.61 and ß -0.97, respectively, p < 0.001) in people living with HIV aged ≥60 years. CONCLUSION: Depressive symptoms, poor cognitive function, and lower satisfaction with social roles predict poorer HRQoL in older people living with HIV. These factors need to be considered when designing targeted interventions.


Subject(s)
HIV Infections , Quality of Life , Male , Humans , Aged , Female , Quality of Life/psychology , Cross-Sectional Studies , HIV Infections/drug therapy , HIV Infections/psychology , Surveys and Questionnaires , Cognition
10.
Proc Nutr Soc ; 83(1): 17-27, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37415490

ABSTRACT

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) improves functional bowel symptoms and is a second-line dietary management strategy for the treatment of irritable bowel syndrome (IBS). The diet is complex and involves three stages: restriction, reintroduction and personalisation and clinical effectiveness is achieved with dietitian-led education; however, this is not always available. The aim of this review is to provide an update on the evidence for using the low FODMAP diet, with a focus on the impact of FODMAP restriction and reintroduction considering long-term management of IBS in a clinical setting. Randomised controlled trials have assessed symptom response, quality of life, dietary intake and changes to the gut microbiota during FODMAP restriction. Systematic reviews and meta-analyses consistently report that FODMAP restriction has a better symptom response compared with control diets and a network analysis reports the low FODMAP diet is superior to other dietary treatments for IBS. Research focused on FODMAP reintroduction and personalisation is limited and of lower quality, however common dietary triggers include wheat, onion, garlic, pulses and milk. Dietitian-led delivery of the low FODMAP diet is not always available and alternative education delivery methods, e.g. webinars, apps and leaflets, are available but remove the personalised approach and may be less acceptable to patients and may introduce safety concerns in terms of nutritional adequacy. Predicting response to the low FODMAP diet using symptom severity or a biomarker is of great interest. More evidence on less restrictive approaches and non-dietitian-led education delivery methods are needed.


Subject(s)
Disaccharides , Irritable Bowel Syndrome , Humans , Monosaccharides/therapeutic use , Quality of Life , FODMAP Diet , Diet , Oligosaccharides , Fermentation
11.
bioRxiv ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-37645953

ABSTRACT

Genome-wide association studies implicate multiple loci in risk for systemic lupus erythematosus (SLE), but few contain exonic variants, rendering systematic identification of non-coding variants essential to decoding SLE genetics. We utilized SNP-seq and bioinformatic enrichment to interrogate 2180 single-nucleotide polymorphisms (SNPs) from 87 SLE risk loci for potential binding of transcription factors and related proteins from B cells. 52 SNPs that passed initial screening were tested by electrophoretic mobility shift and luciferase reporter assays. To validate the approach, we studied rs2297550 in detail, finding that the risk allele enhanced binding to the transcription factor Ikaros (IKZF1), thereby modulating expression of IKBKE. Correspondingly, primary cells from genotyped healthy donors bearing the risk allele expressed higher levels of the interferon / NF-κB regulator IKKϵ. Together, these findings define a set of likely functional non-coding lupus risk variants and identify a new regulatory pathway involving rs2297550, Ikaros, and IKKϵ implicated by human genetics in risk for SLE.

12.
Neuro Oncol ; 26(3): 528-537, 2024 03 04.
Article in English | MEDLINE | ID: mdl-37904541

ABSTRACT

BACKGROUND: Patients with low-grade gliomas (LGG) treated with surgery, generally function well and have a favorable prognosis. However, LGG can affect neurocognitive functioning. To date, little is known about social cognition (SC) in these patients, although impaired SC is related to social-behavioral problems and poor societal participation. Frontal brain areas are important for SC and LGG frequently have a frontal location. Therefore, the aim of the present study was to investigate whether emotion recognition, a key component of SC, was impaired, and related to general cognition, tumor location, laterality, tumor volume, and histopathological characteristics in patients with LGG, postsurgery, and before start of adjuvant therapy. METHODS: A total of 121 patients with LGG were matched with 169 healthy controls (HC). Tumor location [including (frontal) subregions; insula, anterior cingulate cortex, lateral prefrontal cortex (LPFC), orbitofrontal-ventromedial PFC] and tumor volume were determined on MRI scans. Emotion recognition was measured with the Ekman 60 faces test of the Facial Expressions of Emotion-Stimuli and Tests (FEEST). RESULTS: Patients with LGG performed significantly lower on the FEEST than HC, with 33.1% showing impairment compared to norm data. Emotion recognition was not significantly correlated to frontal tumor location, laterality, and histopathological characteristics, and significantly but weakly with general cognition and tumor volume. CONCLUSIONS: Emotion recognition is impaired in patients with LGG but not (strongly) related to specific tumor characteristics or general cognition. Hence, measuring SC with individual neuropsychological assessment of these patients is crucial, irrespective of tumor characteristics, to inform clinicians about possible impairments, and consequently offer appropriate care.


Subject(s)
Cognitive Dysfunction , Glioma , Humans , Emotions , Cognition , Recognition, Psychology , Neuropsychological Tests , Facial Expression
13.
J Palliat Med ; 27(3): 383-387, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38048291

ABSTRACT

Background: Clinician empathy positively impacts patient outcomes. Few studies have assessed the effects of different types of empathic expression. Objective: To describe how families respond when clinicians express empathy in different ways. Design: Prospective, mixed-methods cohort. Setting/Subjects: English and interpreted pediatric inpatient care conferences at a U.S. quaternary hospital between January 1, 2018 and January 1, 2021. Measurements: Directed content analysis of clinician empathic statements and family responses. Results: Of 29 patient-family dyads, 11 (39%) used language interpretation. In response to 80 clinician empathic statements, families expressed agreement or shared more 84% (67/80) of the time. Families shared more about their perspective in response to explore statements 71.4% (10/14) of the time, in response to validate statements 61% (17/28) of the time, and in response to respect/support statements 39% (11/28) of the time. Conclusion: Certain types of empathic statements may be more effective at prompting families to share more about their perspective, a key element of shared decision-making.


Subject(s)
Communication , Empathy , Humans , Child , Prospective Studies , Language , Decision Making, Shared
14.
Ann Am Thorac Soc ; 21(2): 271-278, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37878995

ABSTRACT

Rationale: Lung transplantation can extend the lives of individuals with advanced cystic fibrosis (CF). Until March 2023, the Lung Allocation Score (LAS) was used in the United States to determine transplant priority. Certain clinical events or attributes ("risk events") that are not included in the LAS (e.g., massive hemoptysis) are relatively common and prognostically important in CF and may prompt an exception request to increase priority for donor lungs. The new Lung Composite Allocation Score (CAS) also allows for exceptions based on the same principles. Objectives: To evaluate the frequency of LAS exceptions in persons with CF (PwCFs) listed for lung transplantation and assess whether LAS exceptions are associated with improved waitlist outcomes for PwCFs compared with similarly "at-risk" individuals without LAS exceptions. Methods: A merged dataset combining data from the CF Foundation Patient Registry and the Organ Procurement and Transplantation Network (2005-2019) was used to identify PwCFs listed for lung transplantation. We compared waitlist outcomes between PwCFs with a LAS exception versus those without an exception despite having a risk event. Risk events were defined as an episode of massive hemoptysis, pneumothorax, at least three moderate/severe pulmonary exacerbations, and/or a decrease in forced expiratory volume in 1 second by ⩾30% predicted (absolute) in the prior 12 months. Analyses were performed using competing risk regression with time to transplantation as the primary outcome and death without a transplant as a competing risk. Results: Of 3,538 listings from 3,309 candidates, 2% of listings (n = 81) had at least one exception. Candidates with an exception and those with a risk event but no exception received lung transplants more slowly than people without an exception or risk event (subdistribution hazard ratio [95% confidence interval]: LAS exception cohort, 0.66 [0.52-0.85]; risk event cohort without exceptions, 0.79 [0.72-0.86]). There was no difference between those with LAS exceptions and those at risk without LAS exceptions: subdistribution hazard ratio, 0.84 (0.66-1.08). Conclusions: LAS exceptions are rare in PwCFs listed for lung transplantation. LAS exceptions resulted in a similar time to transplantation for PwCFs compared with similarly at-risk individuals. As we enter the CAS era, these LAS-based results are pertinent to improve risk stratification among PwCFs being considered for lung transplantation.


Subject(s)
Cystic Fibrosis , Lung Transplantation , Humans , United States/epidemiology , Cystic Fibrosis/complications , Cystic Fibrosis/surgery , Hemoptysis , Lung Transplantation/methods , Proportional Hazards Models , Waiting Lists , Lung , Retrospective Studies
15.
J Aging Soc Policy ; 36(1): 141-155, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-37796766

ABSTRACT

Nursing homes receive complaints when actual care provided to residents misaligns with desired care, suggesting that person-centered care (PCC) and honoring resident preferences in care delivery may help prevent complaints from arising. We explore whether nursing home implementation of a PCC tool, the Preferences for Everyday Living Inventory (PELI), is related to measures of complaints. Publicly available data on Ohio nursing homes was used to examine 1,339 nursing home-year observations. Regression techniques were used to evaluate the relationship between the extent of PELI implementation and four complaint outcomes: any complaint, number of complaints, any substantiated complaint, and number of substantiated complaints. Nursing homes with complete PELI implementation were less likely to have any complaints by 4.7% points (P < .05) and any substantiated complaints by 11.5% points (P < .001) as compared to partial PELI implementers. When complete PELI implementers did have complaints, they were fewer than partial PELI implementers. Complete PELI implementers were not immune from receiving complaints; however, the complaints they did receive were fewer in number and less likely to be substantiated as compared to communities who only partially implemented a PCC tool.


Subject(s)
Nursing Homes , Patient-Centered Care , Humans , Ohio , Patient-Centered Care/methods
16.
Data Brief ; 52: 109828, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38105904

ABSTRACT

Coastal observations along the Texas coast are valuable for many stakeholders in diverse domains. However, the management of the collected data has been limited, creating gaps in hydrological and atmospheric datasets. Among these, water and air temperature measurements are particularly crucial for water temperature predictions, especially during freeze events. These events can pose a serious threat to endangered sea turtles and economically valuable fish, which can succumb to hypothermic stunning, making them vulnerable to cold-related illness or death. Reliable and complete water and air temperature measurements are needed to provide accurate predictions of when cold-stunning events occur. To address these concerns, the focus of this paper is to describe the method used to create a complete 10-year dataset that is representative of the upper Laguna Madre, TX using multiple stations and various gap-filling methods. The raw datasets consist of a decade's worth of air and water temperature measurements within the Upper Laguna Madre from 2012 to 2022 extracted from the archives of the Texas Coastal Ocean Observation Network and the National Park Service. Large portions of data from the multiple stations were missing from the raw datasets, therefore a systematic gap-filling approach was designed and applied to create a near-continuous dataset. The proposed imputation method consists of three steps, starting with a short gap interpolation method, followed by a long gap-filling process using nearby stations, and finalized by a second short gap interpolation method. This systematic data imputation approach was evaluated by creating random artificial gaps within the original datasets, filling them using the proposed data imputation method, and assessing the viability of the proposed methods using various performance metrics. The evaluation results help to ensure the reliability of the newly imputed dataset and the effectiveness of the data imputation method. The newly created dataset is a valuable resource that transcends the local cold-stunning issue, offering viable utility for analyzing temporal variability of air and water temperatures, exploring temperature interdependencies, reducing forecasting uncertainties, and refining natural resource and weather advisory decision-making processes. The cleaned dataset with minimal gaps (<2%) is ready and convenient for artificial intelligence and machine learning applications.

17.
Appl Environ Microbiol ; 89(12): e0063023, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38054732

ABSTRACT

IMPORTANCE: Fusaric acid (FA) is an important virulence factor produced by several Fusarium species. These fungi are responsible for wilt and rot diseases in a diverse range of crops. FA is toxic for animals, humans and soil-borne microorganisms. This mycotoxin reduces the survival and competition abilities of bacterial species able to antagonize Fusarium spp., due to its negative effects on viability and the production of antibiotics effective against these fungi. FA biodegradation is not a common characteristic among bacteria, and the determinants of FA catabolism have not been identified so far in any microorganism. In this study, we identified genes, enzymes, and metabolic pathways involved in the degradation of FA in the soil bacterium Burkholderia ambifaria T16. Our results provide insights into the catabolism of a pyridine-derivative involved in plant pathogenesis by a rhizosphere bacterium.


Subject(s)
Burkholderia cepacia complex , Burkholderia , Fusarium , Mycotoxins , Animals , Humans , Mycotoxins/metabolism , Fusaric Acid/metabolism , Burkholderia/metabolism , Burkholderia cepacia complex/metabolism , Fungi/metabolism , Soil , Fusarium/metabolism , Plant Diseases/microbiology
18.
Cell Genom ; 3(11): 100420, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-38020975

ABSTRACT

TRAF1/C5 was among the first loci shown to confer risk for inflammatory arthritis in the absence of an associated coding variant, but its genetic mechanism remains undefined. Using Immunochip data from 3,939 patients with juvenile idiopathic arthritis (JIA) and 14,412 control individuals, we identified 132 plausible common non-coding variants, reduced serially by single-nucleotide polymorphism sequencing (SNP-seq), electrophoretic mobility shift, and luciferase studies to the single variant rs7034653 in the third intron of TRAF1. Genetically manipulated experimental cells and primary monocytes from genotyped donors establish that the risk G allele reduces binding of Fos-related antigen 2 (FRA2), encoded by FOSL2, resulting in reduced TRAF1 expression and enhanced tumor necrosis factor (TNF) production. Conditioning on this JIA variant eliminated attributable risk for rheumatoid arthritis, implicating a mechanism shared across the arthritis spectrum. These findings reveal that rs7034653, FRA2, and TRAF1 mediate a pathway through which a non-coding functional variant drives risk of inflammatory arthritis in children and adults.

19.
Neurobiol Aging ; 132: 154-174, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37837732

ABSTRACT

Amyloid ß (Aß) accumulation is a hallmark of Alzheimer's disease. In adult Drosophila brains, human Aß overexpression harms climbing and lifespan. It's uncertain whether Aß is intrinsically toxic or activates downstream neurodegeneration pathways. Our study uncovers a novel protective role against Aß toxicity: intra-endoplasmic reticulum (ER) protein accumulation with a focus on laminin and collagen subunits. Despite high Aß, laminin B1 (LanB1) overexpression robustly counters toxicity, suggesting a potential Aß resistance mechanism. Other laminin subunits and collagen IV also alleviate Aß toxicity; combining them with LanB1 augments the effect. Imaging reveals ER retention of LanB1 without altering Aß secretion. LanB1's rescue function operates independently of the IRE1α/XBP1 ER stress response. ER-targeted GFP overexpression also mitigates Aß toxicity, highlighting broader ER protein retention advantages. Proof-of-principle tests in murine hippocampal slices using mouse Lamb1 demonstrate ER retention in transduced cells, indicating a conserved mechanism. Though ER protein retention generally harms, it could paradoxically counter neuronal Aß toxicity, offering a new therapeutic avenue for Alzheimer's disease.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Animals , Mice , Humans , Amyloid beta-Peptides/toxicity , Amyloid beta-Peptides/metabolism , Drosophila , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Endoribonucleases/metabolism , Laminin/metabolism , Protein Serine-Threonine Kinases/metabolism , Endoplasmic Reticulum Stress , Endoplasmic Reticulum/metabolism , Collagen/metabolism
20.
Int J Parasitol Parasites Wildl ; 22: 38-42, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37654698

ABSTRACT

A new coccidian species, Eimeria erythrorhynchosi n. sp. (Apicomplexa: Eimeriidae) collected from the American white pelican Pelecanus erythrorhynchos Gmelin 1789, is reported from Toluca city, Mexico. Sporulated oocysts of the new species are ovoidal, 17.5-19.6 × 14.1-14.8 (18.5 × 14.5) µm, with a length/width (L/W) ratio of 1.0-1.5 (1.25); micropyle present, robust and protruding, W: 4.5-5.5, and polar body (1 or 2), L × W: 2.5 (2-3), associated with the micropyle; oocyst residuum absent. Sporocysts are ovoidal, 10.1-11.2 × 6.4-7.1 (10.7 × 6.8) µm, with a length/width (L/W) ratio of 1.0-1.6 (1.3); Stieda and sub-Stieda bodies are both present, but para-Stieda body is absent; sporocyst residuum of diffuse granules. Sporozoites are vermiform, 9.6 × 2.4 µm. The new species is the seventh species of Eimeria recorded in Pelecaniformes and the third in Pelecanidae.

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