The local translation of KNa in dendritic projections of auditory neurons and the roles of KNa in the transition from hidden to overt hearing loss

Local and privileged expression of dendritic proteins allows segregation of distinct functions in a single neuron but may represent one of the underlying mechanisms for early and insidious presentation of sensory neuropathy. Tangible characteristics of early hearing loss (HL) are defined in correlation with nascent hidden hearing loss (HHL) in humans and animal models. Despite the plethora of causes of HL, only two prevailing mechanisms for HHL have been identified, and in both cases, common structural deficits are implicated in inner hair cell synapses, and demyelination of the auditory nerve (AN). We uncovered that N

Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency.

Ninety percent of Americans consume less than the estimated average requirements of dietary vitamin E (vitE). Severe vitE deficiency due to genetic mutations in the tocopherol transfer protein (TTPA) in humans results in ataxia with vitE deficiency (AVED), with proprioceptive deficits and somatosensory degeneration arising from dorsal root ganglia neurons (DRGNs). Single-cell RNA-sequencing of DRGNs was performed in Ttpa-/- mice, an established model of AVED. In stark contrast to expected changes in proprioceptive neurons, Ttpa-/- DRGNs showed marked upregulation of voltage-gated Ca2+ and K+ channels in mechanosensitive, tyrosine-hydroxylase positive (TH+) DRGNs. The ensuing significant conductance changes resulted in reduced excitability in mechanosensitive Ttpa-/- DRGNs. A highly supplemented vitE diet (600 mg dl-α-tocopheryl acetate/kg diet) prevented the cellular and molecular alterations and improved mechanosensation. VitE deficiency profoundly alters the molecular signature and functional properties of mechanosensitive TH+ DRGN, representing an intriguing shift of the prevailing paradigm from proprioception to mechanical sensation

IL-1β maintains the DNA hypermethylation of anti-inflammatory IL-10 gene in a human intestinal epithelial cell line

Intestinal inflammation is a natural process crucial to maintain gut integrity, but its deregulation is involved in the pathogenesis of severe intestinal disorders[1]. Intestinal epithelial cells play a crucial role in the inflammatory response, modulating the immune cell exposure to antigens and by their ability to secrete many inflammatory mediators. IL-1β represents a pivotal player: secreted by infiltrated leucocytes, it induces the expression of several pro-inflammatory genes. Also the anti-inflammatory IL-10, whose function is to terminate the inflammatory process, modulates the intestinal physiology[2]. Recent clinical reports showed that patients with ulcerative colitis in remission phase have significantly higher IL10 gene expression in mucosa compared with active patients and controls[3]. Moreover, in the latest years aberrant epigenetic mechanisms were put in binomial relationship with chronic inflammatory diseases[4]. Previously, we described a demethylation of pro-inflammatory IL6 and IL8 genes in human colonic Caco-2 cells differentiated into an enterocyte-like phenotype and exposed to the inflammatory action of IL-1β[5]. In the present study we evaluate whether the IL-1β treatment affected the methylation status of the anti-inflammatory IL10 gene, in the same in vitro model. Our results showed that IL-1β treatment did not change the hypermethylation status of the IL10 promoter. Moreover, in cell lysates from IL-1β-treated Caco-2 cells, we observed a dose-dependent increase of DNMTs activity and, surprisingly, a decrease of DNMT3b expression. These findings put in evidence the complexity of relationship between IL-1β and DNMTs, and may suggest a potential role of IL-1β as pleiotropic modulator of DNA methylation in Caco-2 cell line

Methylation decrease of BECN1 gene induced by phytochemical Indicaxantin in Caco2 cells: an epigenetic hypothesis of autophagy

Autophagy is a highly conserved catabolic process that degrades and recycles intracellular components through the lysosomes [1]. The role of this process in tumorigenesis and tumor progression is controversial: in the early stages, it can block tumor growth and conversely it can promote its progression in the later stages [2]. The tumor suppressor BECN1 gene, encodes the protein Beclin 1, a marker of autophagy down-regulated in several types of cancer, such as colorectal cancer [3]. There are a lot of both genetic and environmental risk factors for colorectal cancer, including diet: for this reason, in accordance with epidemiological studies, consumption of foods rich in phytochemicals is widely promoted. The betalain indicaxantin (Ind) is a phytochemical from the Opuntia Ficus-Indica fruit having several biological activities, such as antioxidant, anti-inflammatory. It showed antiproliferative and proapoptotic effects in colorectal adenocarcinoma (Caco2) cells where was able to regulate gene expression through modulation of methylation state of DNA at CpG islands [4]. For the first time, using Methylation-Sensitive Restriction Endonuclease PCR (MSRE-PCR), we report that Ind (50 e 100 µM) decreases the methylation of BECN1 promoter in Caco2 cells, to the same extent as 5-azacytidine (Zcyd, positive control). Interestingly, colorimetric detection of DNA Methyltransferases activity, indicates that Ind reduced the activity of these enzymes, like Zcyd did. These preliminary data, indicating that Ind is able to decrease the methylation of BECN1 gene, allow us to propose an epigenetic hypothesis of autophagy regulation in Caco2 cells

Cooperativity of Kv7.4 channels confers ultrafast electromechanical sensitivity and emergent properties in cochlear outer hair cells.

The mammalian cochlea relies on active electromotility of outer hair cells (OHCs) to resolve sound frequencies. OHCs use ionic channels and somatic electromotility to achieve the process. It is unclear, though, how the kinetics of voltage-gated ionic channels operate to overcome extrinsic viscous drag on OHCs at high frequency. Here, we report ultrafast electromechanical gating of clustered Kv7.4 in OHCs. Increases in kinetics and sensitivity resulting from cooperativity among clustered-Kv7.4 were revealed, using optogenetics strategies. Upon clustering, the half-activation voltage shifted negative, and the speed of activation increased relative to solitary channels. Clustering also rendered Kv7.4 channels mechanically sensitive, confirmed in consolidated Kv7.4 channels at the base of OHCs. Kv7.4 clusters provide OHCs with ultrafast electromechanical channel gating, varying in magnitude and speed along the cochlea axis. Ultrafast Kv7.4 gating provides OHCs with a feedback mechanism that enables the cochlea to overcome viscous drag and resolve sounds at auditory frequencies

Phytotoxic and dissuasive activity of Chihuahua desert plants

With the purpose of finding plant compounds with the potential use as herbicides and insecticides, a research was realized with the objective of evaluate the phytotoxic and dissuasive activity of four Chihuahua desert plants. The phytotoxic activity evaluation was tested on Lactuca sativa and Lolium perenne, while the dissuasive activity was realized on three species of phytophagous insects: Myzus persicae, Rhopalosiphum padi and Spodoptera littoralis. Raw extracts were used, the solvents hexane, methanol and ethanol of different plants’ organs (root, steam, leaf and flower) of four species: Fouquieria splendens (ocotillo), Larrea tridentate (governor), Astragalus mollissimus (wild grass) and Pachycereus pecten-aboriginum (echo), by the establishment of in vitro bioassays at a concentration of 10 mg/ml extract/solvent. In the toxicity bioassay, the percentage of germination, root and leaf length were measured. The results showed that the leaf extract of L. tridentata had phytotoxic activity for L. sativa, while for L. perenne the phytotoxicity was observed within the ocotillo, governor and echo extracts. In the dissuasive bioassay, each treatment had 20 repetitions with 10 adult insects per repetition. The methanolic extracts of F. splendens leaf and root, ethanolic extract of A. mollisimus sheet and the ethanolic extract of P. pecten-aboriginum stems showed moderate dissuasive response of feeding against M. persicae, presenting a settlement inhibition index of 53.53, 54.35, 60.00 and 48.84% respectively. Nevertheless, the results indicated that none of the 10 extracts tested on S. littoralis showed significant dissuasive properties for this Lepidoptera, while for R. padi all the tested extracts presented dissuasive properties. The treatments of the four vegetable species evaluated showed defensive or dissuasive properties of moderate to strong feeding against the insects M. persicae and R. padi, presenting interesting potential for being used as insecticides, while the tested extracts that presented phytotoxicity for both lettuce and ryegrass present possibilities for the realization of herbicides

Altered outer hair cell mitochondrial and subsurface cisternae connectomics are candidate mechanisms for hearing loss in mice

Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, ER, and plasma membrane promote regulation of multiple functions, which include intracellular C

The tomato mutant ars1 (altered response to salt stress 1) identifies an R1-type MYB transcription factor involved in stomatal closure under salt acclimation

[EN] A screening under salt stress conditions of a T-DNA mutant collection of tomato (Solanum lycopersicum L.) led to the identification of the altered response to salt stress 1 (ars1) mutant, which showed a salt-sensitive phenotype. Genetic analysis of the ars1 mutation revealed that a single T-DNA insertion in the ARS1 gene was responsible of the mutant phenotype. ARS1 coded for an R1-MYB type transcription factor and its expression was induced by salinity in leaves. The mutant reduced fruit yield under salt acclimation while in the absence of stress the disruption of ARS1 did not affect this agronomic trait. The stomatal behaviour of ars1 mutant leaves induced higher Na+ accumulation via the transpiration stream, as the decreases of stomatal conductance and transpiration rate induced by salt stress were markedly lower in the mutant plants. Moreover, the mutation affected stomatal closure in a response mediated by abscisic acid (ABA). The characterization of tomato transgenic lines silencing and overexpressing ARS1 corroborates the role of the gene in regulating the water loss via transpiration under salinity. Together, our results show that ARS1 tomato gene contributes to reduce transpirational water loss under salt stress. Finally, this gene could be interesting for tomato molecular breeding, because its manipulation could lead to improved stress tolerance without yield penalty under optimal culture conditions.This work was funded by a research project (AGL2012-40150-C01/C02/C03) from the Spanish Ministry of Economy and Competitiveness (MINECO). This work was also supported by grant RYC2010-06369 (Ramon y Cajal Programme) from the MINECO to NF-G and grant E-30-2011-0443170 (JAE-Doc Programme) from the Spanish Council of Scientific Research (CSIC) to IE and BP. The authors have no conflict of interests to declareCampos, JF.; Cara, B.; Perez-Martin, F.; Pineda Chaza, BJ.; Egea, I.; Flores, FB.; Fernandez-Garcia, N.... (2016). The tomato mutant ars1 (altered response to salt stress 1) identifies an R1-type MYB transcription factor involved in stomatal closure under salt acclimation. Plant Biotechnology Journal. 14(6):1345-1356. https://doi.org/10.1111/pbi.124981345135614

STUDY ON NUTRITIONAL AND ELEMENTAL ANALYSIS OF THE SEAWEEDS OF NORTHERN SAMAR, PHILIPINES

The purpose of the study: In this work, the nutritional and elemental analysis of seaweeds in Northern Samar is analyzed. Methodology: The seaweeds of Northern Samar are collected from the intertidal zone, and it was brought back to the College of Science for taxonomic identity.   The nutritional and elemental content of the seaweeds were determined. Main findings: Based on the results obtained a total of 39 species belonging to eighteen (18) families of seaweeds were recorded from different coastal towns in Northern Samar, Philippines.  The results revealed that for seaweeds with the economic value the nutritional and elemental content is comparable to the unknown seaweeds with no economic value.     Implications: The results of the bioavailability of nutrients of this study might be the basis that unknown seaweeds with no economic value can be used directly in the diet and promote health advantage. Originality/Novelty of study: The seaweeds of Northern Samar are not properly documented in comparison with other marine flora.  The results demonstrated that some species of seaweeds collected in Northern Samar with no economic value could also accumulate non-essential elements.  Further studies would surely be a great contribution to our local food and pharmaceutical industries.&nbsp

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development