Biology subjects

Silva, M. C.

Publications and source records attributed to Silva, M. C..

3 recordsLinked to original sources

bioRxiv2020

Exifone is a Potent HDAC1 Activator with Neuroprotective Activity in Human Neuronal Models of Neurodegeneration

Genomic instability caused by a deficiency in the DNA damage response and repair has been linked to age-related cognitive decline and neurodegenerative diseases. Preventing genomic instability that ultimately leads to neuronal death may provide a broadly effective strategy to protect against multiple potential genotoxic stressors. Recently, the zinc-dependent, class I histone deacetylase HDAC1 has been identified as a critical factor for protecting neurons from deleterious effects of DNA damage in Alzheimers disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Translating these observations to a novel neuroprotective therapy for AD, ALS, and FTD may be advanced by the identification of small molecules capable of increasing the deacetylase activity of HDAC1 selectively over other structurally similar HDACs. Here, we demonstrate that exifone, a drug previously shown to be effective in treating cognitive deficits associated with AD and Parkinsons disease, the molecular mechanism of which has remained poorly understood, potently activates the deacetylase activity of HDAC1 and provides protection against genotoxic stress. We show that exifone acts as a mixed, non-essential activator of HDAC1 that is capable of binding to both free and substrate-bound enzyme resulting in an increased relative maximal rate of HDAC1-catalyzed deacetylation. Exifone can directly bind to HDAC1 based upon biolayer interferometry assays with kinetic and selectivity profiling suggesting HDAC1 is preferentially targeted compared to other class I HDACs and the kinase CDK5 that have also been implicated in neurodegeneration. Consistent with a mechanism of deacetylase activation intracellularly, treatment of human induced pluripotent stem cell (iPSC)-derived neuronal cells resulted in globally decreased histone acetylation. Moreover, exifone treatment was neuroprotective in a tauopathy patient iPSC-derived neuronal model subject to oxidative stress. Taken together, these findings reveal exifone as a potent activator of HDAC1-mediated deacetylation, thereby offering a lead for novel therapeutic development aiming to protect genomic integrity in the context of neurodegeneration and aging. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

biochemistry↗

bioRxiv2019

Illuminance affects epidemiological parameters of banana Yellow Sigatoka in Brazil

The Sigatoka leaf spots are among the most important banana diseases. Although less damaging than black sigatoka, yellow sigatoka (Pseudocercospora musae) still prevails in some regions. This study aimed at testing the hypothesis of light interference in monocyclic parameters of yellow sigatoka epidemics. Grande Naine plantlets kept under contrasting shading conditions had their leaves 1 and 2 inoculated. Evaluations were performed for 60 days. For each inoculated leaf, the time until symptom onset (incubation), presence of infectious lesions (latency), and disease severity (extensive leaf necrosis) according to Stovers scale modify per Gauhl (1994), called here only Stovers scale, were registered. Logistic regression was used to assess the relative occurrence risk and survival analysis was used to check the effects of variables on relevant epidemiological parameters. The risks of sporulation and of reaching high severities were lower for plants kept under shading regardless of the acclimation conditions and no effect of leaf age was detected. The logistic regression showed symptoms appearing in both conditions (p=0,85), but have significance difference in occurrence of latent lesions (p=0,013) and necrosis (p<0,0001). The necrosis risk in non-shaded environment arrived 66%. The survival analysis showed significance difference in the time to appear the symptom evaluated in all tested variables (p<0,0001) in function of the cropping system. Lower illuminance negatively affected the incubation, latency and infectious periods, and severity. A shaded system could be tested to produce organic bananas in areas of high risk of occurrence of Yellow sigatoka disease.\n\nSignificance and Impact of the StudyYellow Sigatoka (Pseudocercospora musae) is a banana disease that can cause severe damage if left uncontrolled. Its control is based mostly on fungicides.Our results show that shading downregulates the epidemiological parameters of that disease such as incubation, latent and infectious periods, and symptoms severity. These results can be the basis for testing alternative cropping systems and producing organic bananas.

microbiology↗

bioRxiv2019

Modelling in vitro mycelial growth, sporulation and spore germination of Pseudocercospora musae under different illuminance levels

Banana is one of the most produced fruits in the world. Many diseases infect the culture and yellow sigatoka is one of the most important. Light may interfere in the pre-penetration parameters of the fungus. The aim of this study was to evaluate the action of light on aspects of the life cycle of the causal agent. The action of light was tested in vitro on the mycelial growth, sporulation and germination of the fungus. For the mycelial growth 10 colonies were transferred to each Petri plate, by evaluating the green weight of a plate at each moment, in mg, at zero, 15, 21, 28, 35 and 42 days of cultivation according to different illuminance levels. Under the same conditions, the sporulation was also quantified at 5, 7, 11, 13 and 14 days. For germination, equal volumes of a spore suspension were placed in small glass containers, which then were set in mini-shades (different illuminances). Every 1h, lacto-phenol was added to a glass from each environment paralyzing the growth, at the same time, illuminance measurements were made with a light meter. The data obtained from sporulation (linear relation) and germination (positive exponential behavior) were significant for the illuminance levels tested.\n\nSignificance and Impact of the StudyYellow Sigatoka disease, caused by Pseudocercospora musae, is still one of the most importante banana diseases in Brazil. Its control demands the use of fungicides. New environmental-friendly control methods should be developed. Therefore, the behaviour of both fungus and plant-fungus interaction should be known. We modelled the in vitro behaviour of P. musae in function of light intensity. Our results can help to develop shading strategies to control yellow Sigatoka.

microbiology↗