Postnatal maternal care moderates the effects of prenatal bisphenol exposure on offspring neurodevelopmental, behavioral, and transcriptomic outcomes.

Bisphenols (BP), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and in rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal bisphenol exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal bisphenol exposure and postnatal maternal care on neurodevelopment and behavior in rats. Our findings suggest that the effects of prenatal bisphenol exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal bisphenol exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal bisphenol exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal bisphenol exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal bisphenol exposure and improve health and well-being in human populations.

Psychometric properties of the Chilean version of the quality of life questionnaire for multiple myeloma.

OBJECTIVES: To evaluate the internal consistency and construct validity of the QLQ-MY20 for assessing the quality of life in multiple myeloma survivors in Chile. METHODS: This was a cross-sectional study conducted between March 2020 and December 2022. It involved 118 individuals from two public hospitals. The QLQ-C30 and QLQ-MY20 questionnaires were used. Internal consistency was assessed using Cronbach's alpha(α), and construct validity was evaluated through hypothesis testing (Mann-Whitney and Spearman correlation). RESULTS: The average age of participants was 67.2 years (SD=9.2). Internal consistency for the complete scale was α=0.779, for the "disease symptoms" dimension α=0.671, for the "side effects of treatments" dimension α=0.538, and for the "future perspective" dimension α=0.670. Four of the five construct validity hypotheses were confirmed: women, individuals with worse performance status, those with pain, and those with worse fatigue showed more symptoms. CONCLUSIONS: The Chilean version of the QLQ-MY20 demonstrates adequate internal consistency and construct validity.

Psychometric properties of the Chilean version of the quality of life questionnaire for multiple myeloma / Propriedades psicométricas da versão chilena do questionário de qualidade de vida para mieloma múltiplo / Propiedades psicométricas de la versión chilena del cuestionario de calidad de vida para mieloma múltiple

ABSTRACT Objectives: To evaluate the internal consistency and construct validity of the QLQ-MY20 for assessing the quality of life in multiple myeloma survivors in Chile. Methods: This was a cross-sectional study conducted between March 2020 and December 2022. It involved 118 individuals from two public hospitals. The QLQ-C30 and QLQ-MY20 questionnaires were used. Internal consistency was assessed using Cronbach's alpha(α), and construct validity was evaluated through hypothesis testing (Mann-Whitney and Spearman correlation). Results: The average age of participants was 67.2 years (SD=9.2). Internal consistency for the complete scale was α=0.779, for the "disease symptoms" dimension α=0.671, for the "side effects of treatments" dimension α=0.538, and for the "future perspective" dimension α=0.670. Four of the five construct validity hypotheses were confirmed: women, individuals with worse performance status, those with pain, and those with worse fatigue showed more symptoms. Conclusions: The Chilean version of the QLQ-MY20 demonstrates adequate internal consistency and construct validity.

RESUMO Objetivos: Avaliar consistência interna e validade de construto do QLQ-MY20 para avaliação da qualidade de vida em sobreviventes de mieloma múltiplo no Chile. Métodos: Estudo transversal, realizado entre março de 2020 e dezembro de 2022. Participaram 118 pessoas de dois hospitais públicos. Foram utilizados questionários QLQ-C30 e QLQ-MY20. A consistência interna foi avaliada com alfa de Cronbach(α) e a validade de construto através de testes de hipóteses (Mann Whitney e correlação de Spearman). Resultados: A idade média dos participantes era de 67,2 (DP=9,2) anos. Consistência interna para escala completa (α=0,779), dimensão "sintomas da doença" (α=0,671), dimensão "efeitos colaterais dos tratamentos" (α=0,538) e dimensão "perspectiva de futuro" (α=0,670). Quatro das cinco hipóteses de validade de construto foram confirmadas: as mulheres apresentaram mais sintomas, assim como pessoas com pior estado de desempenho, com dor e com maior fadiga. Conclusões: A versão chilena do QLQ-MY20 apresenta consistência interna adequada e validade de construto.

RESUMEN Objetivos: Evaluar consistencia interna y validez de constructo del QLQ-MY20 para valoración de calidad de vida en sobrevivientes de mieloma múltiple en Chile. Métodos: Estudio transversal, realizado entre marzo 2020 y diciembre 2022. Participaron 118 personas de dos hospitales públicos. Se utilizaron los cuestionarios QLQ-C30 y QLQ-MY20. Fueron evaluadas la consistencia interna con alfa de Cronbach (α) y validez de constructo mediante pruebas de hipótesis (Mann Whitney y correlación de Spearman). Resultados: El promedio de edad de los participantes era 67,2 (DE=9,2) años. Consistencia interna para escala completa (α=0,779), dimensión "síntomas de la enfermedad" (α=0,671), dimensión "efectos secundarios de los tratamientos" (α=0,538) y dimensión "perspectiva de futuro" (α=0,670). Se comprobaron cuatro de las cinco hipótesis de la validez de constructo: presentaron más síntomas las mujeres, personas con peor performance estatus, con dolor y con peor fatiga. Conclusiones: La versión chilena del QLQ-MY20 presenta adecuada consistencia interna y validez de constructo.

Postnatal maternal care moderates the effects of prenatal bisphenol exposure on offspring neurodevelopmental, behavioral, and transcriptomic outcomes.

Bisphenols (BPs), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal BP exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal BP exposure and postnatal maternal care on neurodevelopment and behavior. Our findings suggest that the effects of prenatal BP exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal BP exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal BP exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal BP exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal BP exposure and improve health and well-being in human populations.

Automated maternal behavior during early life in rodents (AMBER) pipeline.

Mother-infant interactions during the early postnatal period are critical for infant survival and the scaffolding of infant development. Rodent models are used extensively to understand how these early social experiences influence neurobiology across the lifespan. However, methods for measuring postnatal dam-pup interactions typically involve time-consuming manual scoring, vary widely between research groups, and produce low density data that limits downstream analytical applications. To address these methodological issues, we developed the Automated Maternal Behavior during Early life in Rodents (AMBER) pipeline for quantifying home-cage maternal and mother-pup interactions using open-source machine learning tools. DeepLabCut was used to track key points on rat dams (32 points) and individual pups (9 points per pup) in postnatal day 1-10 video recordings. Pose estimation models reached key point test errors of approximately 4.1-10 mm (14.39 pixels) and 3.44-7.87 mm (11.81 pixels) depending on depth of animal in the frame averaged across all key points for dam and pups respectively. Pose estimation data and human-annotated behavior labels from 38 videos were used with Simple Behavioral Analysis (SimBA) to generate behavior classifiers for dam active nursing, passive nursing, nest attendance, licking and grooming, self-directed grooming, eating, and drinking using random forest algorithms. All classifiers had excellent performance on test frames, with F1 scores above 0.886. Performance on hold-out videos remained high for nest attendance (F1 = 0.990), active nursing (F1 = 0.828), and licking and grooming (F1 = 0.766) but was lower for eating, drinking, and self-directed grooming (F1 = 0.534-0.554). A set of 242 videos was used with AMBER and produced behavior measures in the expected range from postnatal 1-10 home-cage videos. This pipeline is a major advancement in assessing home-cage dam-pup interactions in a way that reduces experimenter burden while increasing reproducibility, reliability, and detail of data for use in developmental studies without the need for special housing systems or proprietary software.

Investigation of Somatic Mutations in Human Brains Targeting Genes Associated With Parkinson's Disease.

Background: Somatic single nucleotide variant (SNV) mutations occur in neurons but their role in synucleinopathies is unknown. Aim: We aimed to identify disease-relevant low-level somatic SNVs in brains from sporadic patients with synucleinopathies and a monozygotic twin carrying LRRK2 G2019S, whose penetrance could be explained by somatic variation. Methods and Results: We included different brain regions from 26 Parkinson's disease (PD), one Incidental Lewy body, three multiple system atrophy cases, and 12 controls. The whole SNCA locus and exons of other genes associated with PD and neurodegeneration were deeply sequenced using molecular barcodes to improve accuracy. We selected 21 variants at 0.33-5% allele frequencies for validation using accurate methods for somatic variant detection. Conclusions: We could not detect disease-relevant somatic SNVs, however we cannot exclude their presence at earlier stages of degeneration. Our results support that coding somatic SNVs in neurodegeneration are rare, but other types of somatic variants may hold pathological consequences in synucleinopathies.

First Report of Fusarium armeniacum Causing Fusarium Head Blight on Soft Red Winter Wheat in Illinois.

In the summer of 2016, while surveying the diversity of the Fusarium head blight (FHB) causal agent on soft red winter wheat (Triticum aestivum) in Illinois, we identified hundreds of naturally infected plants in five locations. Samples with characteristic symptoms of FHB (bleaching, accompanied by pink/white mycelium) were collected one to three weeks after anthesis. The collected glumes and developing kernels were surface sterilized and plated on sterile media. Single conidia isolates were derived for further work. All isolates were deposited to the USDA-ARS Mycotoxin Prevention and Applied Microbiology Research Unit in Peoria, IL. Among the collection, isolate CMR105 showed characteristics of F. armeniacum growing on PDA with abundant white mycelia and pigments of orange to pink (Suppl. Figure 1B). The CMR105 macroconidia were prominently curved, long, and tapering with a distinct foot shape typical of F. armeniacum (Leslie and Summerell, 2006). CMR105 conidia were produced quickly and abundantly compared to typical isolates such as BMR001, which were rare and slow-growing. The translation elongation factor 1-alpha (EF1-α), RNA polymerase 2 (RPB2), ß-tubulin, and the internal transcribed spacer (ITS) genes were sequenced from selected isolates, including CMR105. The resulting DNA sequences were trimmed and aligned using blast on the Fusarium ID database and NCBI's nr database. For all the genes, isolate CMR105 had a 99% or higher similarity to multiple F. armeniacum accessions (Suppl. Table 1). We then conducted a phylogenetic analysis using the DNA sequences of three concatenated genes (RPB2, ß-tubulin, and ITS). A maximum likelihood tree supported that isolate CMR105 is F. armeniacum (Suppl. Figure 1E). Koch's postulates were carried out in greenhouse experiments on spring wheat cultivar 'Norm'. At anthesis, a spore suspension of 5 x 104 spores per ml was injected into the central spikelet of wheat heads. Three plants were inoculated per isolate and a mock control consisting of water. The inoculated plants were placed into a mist chamber for 48 hours. Symptoms consisting of premature bleaching of multiple spikelets and pink/white coloration were observed one-week post-inoculation. No symptoms were observed on the control. Two weeks post-inoculation, kernels from the wheat heads were collected, surface sterilized with 10% bleach, and plated on PDA. The recovered isolates showed similar colony morphology to the inoculum. Similar results were obtained on field inoculations on soft red winter wheat. F. armeniacum has been reported from the United States, Australia, South Africa, China, and Argentina (Kommedahl et al., 1979; Nichea et al., 2015). To date, F. armeniacum has been reported to cause seed and root rot on soybeans, has been recovered from asymptomatic corn, and more commonly found as a soil saprophyte (Ellis et al., 2012; Leslie and Summerell, 2006; Nichea et al., 2015). We have shown here for the first time that F. armeniacum also causes FHB on wheat in Illinois. In both field and greenhouse assays, our F. armeniacum strain was less aggressive than F. graminearum strains. Recently, F. armeniacum was reported to cause FHB on emmer and spring wheat in New York (Fulcher and Bergstrom, 2020). It is important to note that many species of the genus Fusarium cause FHB. In this report, we show evidence that F. armeniacum is another causal agent of FHB in Illinois and warrants further study and surveillance.

Arachidonyl-2'-chloroethylamide (ACEA), a synthetic agonist of cannabinoid receptor, increases CB1R gene expression and reduces dyskinesias in a rat model of Parkinson's disease.

l-Dopa is the most effective drug used for Parkinson's disease (PD), but after long-term treatment, the vast majority of PD patients develop abnormal involuntary movements (AIMs) termed l-Dopa-induced dyskinesia (LID). Cannabinoid receptors in the basal ganglia can modulate motor functions, but their role in the treatment of LID is controversial. Therefore, the aim of this study is to evaluate the motor behavior and mRNA expression of the cannabinoid receptor-1 (CB1R), encoded by the Cnr1 gene, in the striatum and globus pallidus of a 6-hydroxydopamine rat model of PD. The evaluated rats had 6-hydroxydopamine-induced injury, LID, and LID treated with arachidonyl-2'-chloroethylamide (ACEA), a cannabinoid receptor agonist. Contralateral turns and AIMs were recorded to assess motor behavior. Gene expression was quantified by reverse transcription coupled with quantitative polymerase chain reaction using TaqMan probes. Behavioral evaluations demonstrated that dyskinetic rats treated with ACEA had a significant reduction in AIMs compared to the dyskinetic group. The expression of CB1R mRNA was significantly decreased in the 6-hydroxydopamine-injured and dyskinetic rats, compared to intact rats. The striata of dyskinetic rats treated with ACEA exhibited highly significant increases in CB1R mRNA expression. Contrary to results in the striatum, a lower CB1R expression was observed in globus pallidus from dyskinetic ACEA-treated group. In summary, significant differences in mRNA expression of CB1R were found between the evaluated groups of rats, suggesting the occurrence of compensatory mechanisms that may result in the ACEA-mediated reduction of dyskinesias in a rat model of PD.

Investigation of somatic CNVs in brains of synucleinopathy cases using targeted SNCA analysis and single cell sequencing.

Synucleinopathies are mostly sporadic neurodegenerative disorders of partly unexplained aetiology, and include Parkinson's disease (PD) and multiple system atrophy (MSA). We have further investigated our recent finding of somatic SNCA (α-synuclein) copy number variants (CNVs, specifically gains) in synucleinopathies, using Fluorescent in-situ Hybridisation for SNCA, and single-cell whole genome sequencing for the first time in a synucleinopathy. In the cingulate cortex, mosaicism levels for SNCA gains were higher in MSA and PD than controls in neurons (> 2% in both diseases), and for MSA also in non-neurons. In MSA substantia nigra (SN), we noted SNCA gains in > 3% of dopaminergic (DA) neurons (identified by neuromelanin) and neuromelanin-negative cells, including olig2-positive oligodendroglia. Cells with CNVs were more likely to have α-synuclein inclusions, in a pattern corresponding to cell categories mostly relevant to the disease: DA neurons in Lewy-body cases, and other cells in the striatonigral degeneration-dominant MSA variant (MSA-SND). Higher mosaicism levels in SN neuromelanin-negative cells may correlate with younger onset in typical MSA-SND, and in cingulate neurons with younger death in PD. Larger sample sizes will, however, be required to confirm these putative findings. We obtained genome-wide somatic CNV profiles from 169 cells from the substantia nigra of two MSA cases, and pons and putamen of one. These showed somatic CNVs in ~ 30% of cells, with clonality and origins in segmental duplications for some. CNVs had distinct profiles based on cell type, with neurons having a mix of gains and losses, and other cells having almost exclusively gains, although control data sets will be required to determine possible disease relevance. We propose that somatic SNCA CNVs may contribute to the aetiology and pathogenesis of synucleinopathies, and that genome-wide somatic CNVs in MSA brain merit further study.

Field pathogenomics of Fusarium head blight reveals pathogen transcriptome differences due to host resistance.

Fusarium head blight (FHB), caused by Fusarium graminearum and other Fusarium species, is a detrimental disease that affects small grains such as wheat around the world. Management of FHB is difficult, and surveillance as well as a better understanding of pathogen aggressiveness is needed for improved control. F. graminearum disease severity varies depending on the resistance of the host genotype. In this study, we used the field pathogenomics method to investigate gene expression and population structure of isolates collected from wheat lines of varying resistance levels (susceptible, intermediate, and resistant) as well as an axenic control. Differential gene expression was found among isolates collected from different host genotypes. Candidate gene sets were identified for both F. graminearum infection of specific host genotypes and general infection to wheat. Population structure of isolates from different resistance level sources was the same, with all isolates belonging to the NA1 population.

Evaluation of the detection of GBA missense mutations and other variants using the Oxford Nanopore MinION.

BACKGROUND: Mutations in GBA cause Gaucher disease when biallelic and are strong risk factors for Parkinson's disease when heterozygous. GBA analysis is complicated by the nearby pseudogene. We aimed to design and validate a method for sequencing GBA using long reads. METHODS: We sequenced GBA on the Oxford Nanopore MinION as an 8.9 kb amplicon from 102 individuals, including patients with Parkinson's and Gaucher diseases. We used NanoOK for quality metrics, NGMLR to align data (after comparing with GraphMap), Nanopolish and Sniffles to call variants, and WhatsHap for phasing. RESULTS: We detected all known missense mutations in these samples, including the common p.N409S (N370S) and p.L483P (L444P) in multiple samples, and nine rarer ones, as well as a splicing and a truncating mutation, and intronic SNPs. We demonstrated the ability to phase mutations, confirm compound heterozygosity, and assign haplotypes. We also detected two known risk variants in some Parkinson's patients. Rare false positives were easily identified and filtered, with the Nanopolish quality score adjusted for the number of reads a very robust discriminator. In two individuals carrying a recombinant allele, we were able to detect and fully define it in one carrier, where it included a 55-base pair deletion, but not in another one, suggesting a limitation of the PCR enrichment method. Missense mutations were detected at the correct zygosity, except for the case where the RecNciI one was missed. CONCLUSION: The Oxford Nanopore MinION can detect missense mutations and an exonic deletion in this difficult gene, with the added advantages of phasing and intronic analysis. It can be used as an efficient research tool, but additional work is required to exclude all recombinants.

Influence of race, acculturation, and socioeconomic status on tendency toward overweight in Asian-American and Mexican-American early adolescent females.

BACKGROUND: Health disparities in chronic disease prevalence exist in the United States among racial/ethnic groups. This study explores relationships between physical, socioeconomic, and cultural characteristics of a multi-ethnic sample of early adolescent females which may assist health educators in designing programs targeting these groups. METHODS: Mexican-American and Asian-American sixth grade females (n = 144) were enrolled in Adequate Calcium Today. Physical measurements included weight, height, and BMI. Dual energy X-ray absorptiometry determined percent body fat (%BF). Socioeconomic status was determined by enrollment in free or reduced meal program (FRMP). An adapted Acculturation Rating Scale for Mexican-Americans-II (ARSMA-II) measured acculturation. RESULTS: Mexican-Americans had greater height, BMI, %BF, and a greater tendency toward overweight (P < 0.01) than Asian-American. Asian-Americans were more acculturated than MA (P < 0.005), attributed to a lower ethnic orientation scale score. Within Asian-Americans, %BF was higher among FRMP participants than non-participants (P < 0.05). DISCUSSION: Income and acculturation may affect tendency toward chronic disease.