XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair

Genetic defects in the repair of DNA single-strand breaks (SSBs) can result in neurological disease triggered by toxic activity of the single-strand-break sensor protein PARP1. However, the mechanism(s) by which this toxic PARP1 activity triggers cellular dysfunction are unclear. Here we show that human cells lacking XRCC1 fail to rapidly recover transcription following DNA base damage, a phenotype also observed in patient-derived fibroblasts with XRCC1 mutations and Xrcc1−/− mouse neurons. This defect is caused by excessive/aberrant PARP1 activity during DNA base excision repair, resulting from the loss of PARP1 regulation by XRCC1. We show that aberrant PARP1 activity suppresses transcriptional recovery during base excision repair by promoting excessive recruitment and activity of the ubiquitin protease USP3, which as a result reduces the level of monoubiquitinated histones important for normal transcriptional regulation. Importantly, inhibition and/or deletion of PARP1 or USP3 restores transcriptional recovery in XRCC1−/− cells, highlighting PARP1 and USP3 as possible therapeutic targets in neurological disease.

Evaluation of the chemical composition of aquatic environments with leaf litter decomposition of Eucalyptus urophylla S.T. Blake (Myrtaceae) and their toxicity in Allium cepa L. (Amaryllidaceae)

Allelochemicals from eucalyptus released into the environment, mainly by leaves, can have a toxic effect on local biota, including in aquatic environments. Therefore, the present study evaluates the toxic activity of the water containing leaves of Eucalyptus urophylla S.T. Blake (Myrtaceae) in decomposition using Allium cepa L. (Amaryllidaceae) as a test organism. The toxicity and the cytotoxicity evaluation were performed using onion bulbs (A. cepa). The toxicity was assessed by inhibiting root growth. The cytotoxicity was evaluated by using a comparison of the mitotic index (MI) and the negative control. The extraction of eucalyptus metabolites from water of the decomposition tests and creek water was performed by solid-phase microextraction (SPME). The chemical characterization was done by gas chromatography coupled to mass spectrometry (GC-MS). There was inhibition of the root growth of A. cepa, indicating toxicity of the compounds released in the water during the decomposition. The cytotoxicity tests did not indicate a toxic effect. However, there were identified some mutations, cell death, and morphological changes in the roots. 26 compounds were identified on samples of water acquired from decomposition tests.Fenchone, 2-ethyl-1-hexanol, cis-dihydrocarvone, and trans-dihydrocarvone were identified in all samples. The results highlight the importance of studies and monitoring of aquatic environments near eucalyptus.

Antibacterial Activities and Toxicity of Streptosporangium sp. SM1P

This study aims to explore the anti-bacterial and toxicity activities from a rare actinobacterium isolated from mangrove, Mempawah District, West Kalimantan. The mangrove mud sample from Mempawah district was inoculated on ISP4 agar using a pour plate method. After 4 days of incubation, a colony of suspected actinobacterium was appeared, then isolated and coded as SM1P. SM1P was characterized based on morphological and biochemical traits and identified as a genus of Streptroporangium then called Streptroporangium sp. SM1P. Streptroporangium sp. SM1P was carried out anti-bacterial assay on both ISP1 agar and ISP4 agar media using the cross-streak method for the solid-state fermentation. The result showed that Streptroporangium sp. SM1P could inhibit Streptococcus sp. and Salmonella typhi on ISP1 agar and treptococcus sp., Escherichia coli, Vibrio cholerae, Staphylococcus aureus and Salmonella typhi on ISP4 agar. Streptroporangium sp. SM1P was cultivated on ISP1 broth and extracted using ethyl acetate, then evaporated to obtain crude extract. The crude extract was used for anti-bacterial assay (well-diffusion method for liquid-state fermentation) and toxicity assay (brine shrimp lethality test). The crude extract was active against 2 of the test bacteria (Streptococcus sp. and E. coli). The best medium and state fermentation for anti-bacterial assay were ISP4 agar with the condition of solid-state fermentation. The extract SM1P prepared on ISP1 broth showed toxic activity based on LC50 (106.094 µg/mL). Therefore, Streptroporangium sp. SM1P have a potential source to explore secondary metabolites having anti-bacterial and toxicity activities.

Antimicrobial and Toxic Activity of Citronella Essential Oil (Cymbopogon nardus), and Its Effect on the Growth and Metabolism of Gilthead Seabream (Sparus aurata L.)

Aquaculture procedures usually induce stress that affects the physiological status of fish. For this reason, the inclusion of additives in fish feeds to palliate stress might be a good alternative. This study aimed to assess the antimicrobial activity of citronella (Cymbopogon nardus) essential oil (CEO) against bacterial pathogens and to determine its dietary impact on the growth performance of Sparus aurata. In vitro tests confirmed that CEO possesses antimicrobial activity against several fish-specific pathogens. For the in vivo tests, three experimental groups were fed for 60 days with different concentrations of CEO: CTRL (0 mL kg−1 fish feed); CEO1 (1 mL kg−1 fish feed); and CEO2 (2 mL kg−1 fish feed). At the end of the experiment, the physiological status was characterized. Subsequently, the specimens of the CTRL and CEO2 groups were subjected to a challenge with an injection of Poly I:C for immune stimulation. Although S. aurata individuals tolerated CEO inclusion without compromising growth performance, it significantly reduced glycogen in the CEO2 group, concomitant to an increment of total peripheral leucocytes. Moreover, different hematological profiles’ responsive patterns against an inflammatory stimulus were observed. In conclusion, our results suggest that the use of CEO as a fish feed additive can prevent bacterial outbreaks and improve potential in vivo disease resistance in S. aurata without negatively affecting growth.

Chemical Composition and Insecticidal Potential of Six Essential Oils from Morocco against Dactylopius opuntiae (Cockerell) under Field and Laboratory Conditions

The carmine cochineal Dactylopius opuntiae (Cockerell) is the major insect pest of the prickly-pear cactus Opuntia ficus-indica (L.) in Morocco. The present study investigated the insecticidal activities of six essential oils (EOs) against nymphs and adult females of D. opuntiae applied singly or in combination with a detergent under laboratory and field conditions. Under laboratory conditions, M. pulegium and O. vulgare L. essential oils showed a high level of insecticidal activity at 5%, with 98% and 92% females’ mortality, respectively, 5 days after treatments. The M. pulegium and O. vulgaris oils at 5% applied in combination with black soap at (60 g/L) induced the highest toxic activity on adult females, 100% and 96% at 5 days after treatments, respectively. Under field conditions, M. pulegium and O. vulgare oils at 5% in combination with black soap (60 g/L) showed the highest adult female mortalities with 96.33 and 92.56%, respectively, 7 days after the first application. The double application of M. pulegium oil at 5% significantly increased the mortality of adult females up to 91%, 5 days after the second spray. GC-MS analysis revealed that the most abundant constituent of M. pulegium and O. vulgare oils was pulegone (84.69%) and durenol (76.53%), respectively. These findings showed that the use of M. pulegium and O. vulgare in combination with black soap or in double sprays could be incorporated in the management package for the control of the wild cochineal D. opuntiae, as a safe and natural alternative to chemical insecticides.

Disruption of nucleoid expanded conformation by toxic aberrant proteins synthesized in Escherichia coli

Aminoglycoside antibiotics interfere with selection of cognate tRNAs during translation, resulting in the production of aberrant proteins that are the ultimate cause of the antibiotic bactericidal effect. To determine if these aberrant proteins are recognized as substrates by the cell’s protein quality control machinery, we studied whether the heat shock (HS) response was activated following exposure of Escherichia coli to the aminoglycoside kanamycin (Kan). Levels of the HS transcription factor σ32 increased about 10-fold after exposure to Kan, indicating that at least some aberrant proteins were recognized as substrates by the molecular chaperone DnaK. To investigate whether toxic aberrant proteins therefore might escape detection by the QC machinery, we studied model aberrant proteins that had a bactericidal effect when expressed in E. coli from cloned genes. As occurred following exposure to Kan, levels of σ32 were permanently elevated following expression of an acutely toxic 48-residue protein (ARF48), indicating that toxic activity and recognition by the QC machinery are not mutually exclusive properties of aberrant proteins, and that the HS response was blocked in these cells at some step downstream of σ32 stabilization. This block could result from halting of protein synthesis or from radial condensation of nucleoids, both of which occurred rapidly following ARF48 induction. Nucleoids were similarly condensed following expression of toxic aberrant secretory proteins, suggesting that transertion of inner membrane proteins, a process that expands nucleoids into an open conformation that promotes growth and gene expression, was disrupted in these cells. The 48-residue ARF48 protein would be well-suited for structural studies to further investigate the toxic mechanism of aberrant proteins.

The Role of Vitamins in Neurodegenerative Disease: An Update

Acquiring the recommended daily allowance of vitamins is crucial for maintaining homeostatic balance in humans and other animals. A deficiency in or dysregulation of vitamins adversely affects the neuronal metabolism, which may lead to neurodegenerative diseases. In this article, we discuss how novel vitamin-based approaches aid in attenuating abnormal neuronal functioning in neurodegeneration-based brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, and Prion disease. Vitamins show their therapeutic activity in Parkinson’s disease by antioxidative and anti-inflammatory activity. In addition, different water- and lipid-soluble vitamins have also prevented amyloid beta and tau pathology. On the other hand, some results also show no correlation between vitamin action and the prevention of neurodegenerative diseases. Some vitamins also exhibit toxic activity too. This review discusses both the beneficial and null effects of vitamin supplementation for neurological disorders. The detailed mechanism of action of both water- and lipid-soluble vitamins is addressed in the manuscript. Hormesis is also an essential factor that is very helpful to determine the effective dose of vitamins. PubMed, Google Scholar, Web of Science, and Scopus were employed to conduct the literature search of original articles, review articles, and meta-analyses.

Botrytis cinerea BcPTP1 is a late infection phase, cysteine rich protein cytotoxic effector

Botrytis cinerea is a broad-host-range necrotrophic phytopathogen responsible for serious crops diseases. To facilitate infection, B. cinerea secretes a large number of effectors that induce plant cell death. In screening secretome data of B. cinerea during infection stage, we identified a phytotoxic protein (BcPTP1) that can also induce immune resistance in plants. BcPTP1 is a small (90 aa), cysteine rich protein without any known domains. Transiently expression of BcPTP1 in leaves caused chlorosis that intensifies with time and eventually lead to cell death. Point mutations in eight of the 10 cysteine residues of BcPTP1 abolished the toxic effect, however residual toxic activity remained after heating the peptide, suggesting contribution of unknown epitopes to protein phytotoxic effect. The transcript level of the bcptp1 gene was low during the first 36 h after inoculation and increased sharply upon transition to the late infection stage, suggesting a role of BcPTP1 in lesion spreading. While statistically insignificant, deletion of the bcptp1 gene led to slightly smaller lesions on bean leaves. Further analyses indicated that BcPTP1 is internalized into plant cells after secreting into the apoplast and its phytotoxic effect is negatively regulated by the receptor-like kinases BAK1 and SOBIR1. Collectively, our findings show that BcPTP1 is a virulence factor that toxifies the host cells and facilitates lesion spreading during the late infection stage.