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Objective: To determine the current practice in genetic testing for patients with apparently sporadic motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) and asymptomatic at-risk relatives of familial MND/ALS patients seen in specialized care centers in the UK. Methods: An online survey with 10 questions distributed to specialist healthcare professionals with a role in requesting genetic testing working at MND/ALS care centers. Results: Considerable variation in practice was found. Almost 30% of respondents reported some discomfort in discussing genetic testing with MND/ALS patients and a majority (77%) did not think that all patients with apparently sporadic disease should be routinely offered genetic testing at present. Particular concerns were identified in relation to testing asymptomatic at-risk individuals and the majority view was that clinical genetics services should have a role in supporting genetic testing in MND/ALS, especially in asymptomatic individuals at-risk of carrying pathogenic variants. Conclusions: Variation in practice in genetic testing among MND/ALS clinics may be driven by differences in experience and perceived competence, compounded by the increasing complexity of the genetic underpinnings of MND/ALS. Clear and accessible guidelines for referral pathways between MND/ALS clinics and clinical genetics may be the best way to standardize and improve current practice, ensuring that patients and relatives receive optimal and geographically equitable support. [ABSTRACT FROM AUTHOR]

Aeschynomene (Aeschynomene americana L.) is a warm‐season annual legume forage used in tropical and subtropical regions; however, there is limited information on agronomic and environmental benefits of aeschynomene when overseeded into bahiagrass (Paspalum notatum Flüggé) swards. The objective of this study was to evaluate the effects of overseeding aeschynomene or applying N fertilizer to existing bahiagrass on forage characteristics, atmospheric N fixation, and N2O‐N emissions. The study was conducted in Ona, FL, from April 2019 to March 2021. Treatments were the split‐plot arrangement of bahiagrass‐aeschynomene or bahiagrass monoculture (main plot) and N fertilization level (0 or 60 kg N ha−1; subplot), distributed in a randomized complete block design with four replicates. Nitrogen fixation was estimated in plots receiving no N fertilization. The static chamber technique was used to estimate N2O‐N emissions. Overseeding aeschynomene did not increase forage accumulation (mean = 1300 kg dry matter [DM] ha−1 harvest−1) or N2O emissions (mean = 15 g N2O‐N ha−1 per day), but increased forage crude protein (CP) concentration (from 98 to 108 g kg−1) when compared to bahiagrass monoculture. Nitrogen fertilization increased forage accumulation (from 1200 to 1400 kg DM ha−1 per harvest) but it did not affect aeschynomene N fixation (84% N derived from atmospheric fixation [Ndfa]). Nitrous oxide emissions had significant temporal variability across all treatments; however, there were no differences in accumulated N2O‐N emissions among treatments (mean = 2.4 kg N2O‐N ha−1 per year). Overseeding aeschynomene is an effective management practice to increase forage CP concentration in pastures without increasing N2O‐N emissions. Core Ideas: Overseeding aeschynomene into bahiagrass increased sward bahiagrass‐aeschynomene forage nutritive value.Nitrogen fertilization increased 18% forage accumulation of bahiagrass.Forage accumulation was the main factor affecting legume atmospheric N fixation.Overseeding aeschynomene into bahiagrass pastures had no impact on soil N2O‐N emissions. [ABSTRACT FROM AUTHOR]

Inclusions of pathogenic deposits containing TAR DNA-binding protein 43 (TDP-43) are evident in the brain and spinal cord of patients that present across a spectrum of neurodegenerative diseases. For instance, the majority of patients with sporadic amyotrophic lateral sclerosis (up to 97%) and a substantial proportion of patients with frontotemporal lobar degeneration (~45%) exhibit TDP-43 positive neuronal inclusions, suggesting a role for this protein in disease pathogenesis. In addition, TDP-43 inclusions are evident in familial ALS phenotypes linked to multiple gene mutations including the TDP-43 gene coding (TARDBP) and unrelated genes (eg, C9orf72). While TDP-43 is an essential RNA/DNA binding protein critical for RNA-related metabolism, determining the pathophysiological mechanisms through which TDP-43 mediates neurodegeneration appears complex, and unravelling these molecular processes seems critical for the development of effective therapies. This review highlights the key physiological functions of the TDP-43 protein, while considering an expanding spectrum of neurodegenerative diseases associated with pathogenic TDP-43 deposition, and dissecting key molecular pathways through which TDP-43 may mediate neurodegeneration. [ABSTRACT FROM AUTHOR]

Mutations in TARDBP, encoding Tar DNA binding protein-43 (TDP43), cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Attempts to model TDP43 dysfunction in mice have used knockouts or transgenic overexpressors, which have revealed the difficulties of manipulating TDP43, whose level is tightly controlled by auto-regulation. In a complementary approach, to create useful mouse models for the dissection of TDP43 function and pathology, we have identified a nonsense mutation in the endogenous mouse Tardbp gene through screening an N-ethyl-N-nitrosourea (ENU) mutant mouse archive. The mutation is predicted to cause a Q101X truncation in TDP43. We have characterised TardbpQ101X mice to investigate this mutation in perturbing TDP43 biology at endogenous expression levels. We found the TardbpQ101X mutation is homozygous embryonic lethal, highlighting the importance of TDP43 in early development. Heterozygotes (Tardbp+/Q101X) have abnormal levels of mutant transcript, but we find no evidence of the truncated protein and mice have similar full-length TDP43 protein levels as wildtype littermates. Nevertheless, Tardbp+/Q101X mice have abnormal alternative splicing of downstream gene targets, and limb-clasp and body tone phenotypes. Thus the nonsense mutation in Tardbp causes a mild loss-of-function phenotype and behavioural assessment suggests underlying neurological abnormalities. Due to the role of TDP43 in ALS, we investigated potential interactions with another known causative gene, mutant superoxide dismutase 1 (SOD1). Tardbp+/Q101X mice were crossed with the SOD1G93Adl transgenic mouse model of ALS. Behavioural and physiological assessment did not reveal modifying effects on the progression of ALS-like symptoms in the double mutant progeny from this cross. In summary, the TardbpQ101X mutant mice are a useful tool for the dissection of TDP43 protein regulation, effects on splicing, embryonic development and neuromuscular phenotypes. These mice are freely available to the community. [ABSTRACT FROM AUTHOR]

Background: Thousands of chemical compounds are used in paint products, like pigments, extenders, binders, additives, and solvents (toluene, xylene, ketones, alcohols, esters, and glycol ethers). Paint manufacture workers are potentially exposed to the chemicals present in paint products although the patterns and levels of exposure to individual agents may differ from those of painters. The aim of the present study was to evaluate genome damage induced in peripheral blood lymphocytes and oral mucosa cells of paint industry workers. Materials and Methods: Genotoxicity was evaluated using the alkaline Comet assay in blood lymphocytes and oral mucosa cells, and the Micronucleus test in oral mucosa cells. For the micronucleus test in exfoliated buccal cells, no significant difference was detected between the control and paint industry workers. Results: The Comet assay in epithelia buccal cells showed that the damage index (DI) and damage frequency (DF) observed in the exposed group were significantly higher relative to the control group (P≤0.05). In the same way, the Comet assay data in peripheral blood leukocytes showed that both analysis parameters (DI and DF) were significantly greater than that for the control group (P≤0.05). Conclusions: Chronic occupational exposure to paints may lead to a slightly increased risk of genetic damage among paint industry workers. [ABSTRACT FROM AUTHOR]