Nucleotide sequence reagents are verifiable experimental reagents in biomedical publications, because their sequence identities can be independently verified and compared with associated text descriptors. We have previously reported that incorrectly identified nucleotide sequence reagents are characteristic of highly similar human gene knockdown studies, some of which have been retracted from the literature on account of possible research fraud. Because of the throughput limitations of manual verification of nucleotide sequences, we developed a semi-automated fact checking tool, Seek & Blastn, to verify the targeting or non-targeting status of published nucleotide sequence reagents. From previously described and unknown corpora of 48 and 155 publications, respectively, Seek & Blastn correctly extracted 304/342 (88.9%) and 1066/1522 (70.0%) nucleotide sequences and a predicted targeting/ non-targeting status. Seek & Blastn correctly predicted the targeting/ non-targeting status of 293/304 (96.4%) and 988/1066 (92.7%) of the correctly extracted nucleotide sequences. A total of 38/39 (97.4%) or 31/79 (39.2%) Seek & Blastn predictions of incorrect nucleotide sequence reagent use were correct in the two literature corpora. Combined Seek & Blastn and manual analyses identified a list of 91 misidentified nucleotide sequence reagents, which could be built upon through future studies. In summary, incorrect nucleotide sequence reagents represent an under-recognized source of error within the biomedical literature, and fact checking tools such as Seek & Blastn may help to identify papers and manuscripts affected by these errors.

Current evidence from several small studies suggests that omega-3 and soy isoflavone supplementation provides an effective means of reducing arterial stiffness. There was little research that explored intakes of herbal medicines or micronutrients in the treatment of arterial stiffness, and this remains an area of potential research.

Despite contemporary interest in slow-wave sleep and dementia pathology, our findings implicate REM sleep mechanisms as predictors of clinical dementia.

Background Pathological forms of TAR DNA-binding protein 43 (TDP-43) are present in motor neurons of almost all amyotrophic lateral sclerosis (ALS) patients, and mutations in TDP-43 are also present in ALS. Loss and gain of TDP-43 functions are implicated in pathogenesis, but the mechanisms are unclear. While the RNA functions of TDP-43 have been widely investigated, its DNA binding roles remain unclear. However, recent studies have implicated a role for TDP-43 in the DNA damage response. Methods We used NSC-34 motor neuron-like cells and primary cortical neurons expressing wildtype TDP-43 or TDP-43 ALS associated mutants (A315T, Q331K), in which DNA damage was induced by etoposide or H2O2 treatment. We investigated the consequences of depletion of TDP-43 on DNA repair using small interfering RNAs. Specific non homologous end joining (NHEJ) reporters (EJ5GFP and EJ2GFP) and cells lacking DNA-dependent serine/threonine protein kinase (DNA-PK) were used to investigate the role of TDP-43 in DNA repair. To investigate the recruitment of TDP-43 to sites of DNA damage we used single molecule super-resolution microscopy and a co-immunoprecipitation assay. We also investigated DNA damage in an ALS transgenic mouse model, in which TDP-43 accumulates pathologically in the cytoplasm. We also examined fibroblasts derived from ALS patients bearing the TDP-43 M337V mutation for evidence of DNA damage. Results We demonstrate that wildtype TDP-43 is recruited to sites of DNA damage where it participates in classical NHEJ DNA repair. However, ALS-associated TDP-43 mutants lose this activity, which induces DNA damage. Furthermore, DNA damage is present in mice displaying TDP-43 pathology, implying an active role in neurodegeneration. Additionally, DNA damage triggers features typical of TDP-43 pathology; cytoplasmic mis-localisation and stress granule formation. Similarly, inhibition of NHEJ induces TDP-43 mis-localisation to the cytoplasm. Conclusions This study reveals that TDP-43 functions in DNA repair, but loss of this function triggers DNA damage and is associated with key pathological features of ALS.

Background: Although arterial stiffness has recently been confirmed as a predictor of