Modalities of NADP-malic enzyme activities under light and darkness indicate its regulation with reference to C4 weed

NADP –ME is the key enzyme for decarboxylation reactions in C4 CO2 concentration pathways. So, Amaranthus viridis has been evaluated with regards to photosynthetic NADP-malic enzyme for its response under light and darkness. Illumination (1000–1200 µEm-2s-1) for 40 minutes under 2 mM bicarbonate (HCO3-) sensitivity increased activity by 1.97 & 3.77-fold over darkness under 4.0 mM and 0.01 mM malate respectively. Limiting (0.01 mM) and saturated (4.0 mM) malate concentration had significant changes in enzyme activities. The different kinetic parameters indicated had the feedback inhibition under illumination. The activity with the inducer (citrate and succinate) and inhibitor (pyruvate and oxalate) was significant with substrate concentrations. Dithiol had reduced the activity by inhibition of the diminishing effect of light activation treatment. Therefore, NADP-ME is stringently regulated by redox changes with illumination as a key factor. Moreover, the pattern of polymorphic gene expression may be supportive in molecular modulation under light/darkness. This study may support the role of NADP-ME as a biomarker for C4 weed species under oxidative stress through light/darkness.

Hardwired

Sociologist Nikolas Rose has posited the emergence of a “neurochemical self” organized around the assumption that our personal characteristics, moods and desires arise from our brain chemicals, and are amenable to molecular modulation through psychiatric drugs. Drawing on clinical ethnography of a series of support groups run by and for individuals diagnosed with Asperger’s syndrome and other autism spectrum conditions, this chapter charts the emergence of a contrasting model of the “neurostructural” self, oriented around the concept of developmental disability and its presumption of fixed innateness and lifelong course. In rejecting the demands for flexibility and adaptation entailed in neurochemical selfhood, this counterdiscourse of hardwired genetic and synaptic brain structure functions as a form of resistance against the demand for constant fluidity and change that characterizes late modernity. However, its core assumptions of a self that is fixed and inalterable are increasingly threatened by the ascendance of neural plasticity as a new mode of both conceptualizing and intervening on the self.

TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients

ObjectivesTwo of the main target tissues of SARS-coronavirus 2 are the oral cavity pharynx-larynx epithelium, the main virus entry site, and the lung epithelium. The virus enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. Herein we aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity-pharynx-larynx and lung tissues as well as neoplastic tissues from the same histological areas. The information provided in this study may contribute to better understanding of SARS-coronavirus 2 ability to interact with different biological systems and contributes to cumulative knowledge on potential mechanisms to inhibit its diffusion.Materials and MethodsThe study has been conducted using The Cancer Genome Atlas (TCGA) and the Regina Elena Institute (IRE) databases and validated by experimental model in HNSCC and Lung cancer cells. Data from one COVID19 positive patient who was operated on for HNSCC was also included. We have analyzed 478 tumor samples and 44 normal samples from TCGA HNSCC cohort for whom both miRNA and mRNA sequencing was available. The dataset included 391 HPV- and 85 HPV+ cases, with 331 P53 mutated and 147 P53 wild type cases respectively. 352 out of 478 samples were male and 126 female. In IRE cohort we analyzed 66 tumor samples with matched normal sample for miRNA profiling and 23 tumor\normal matched samples for mRNA profiling. 45 out of 66 tumors from IRE cohort were male and 21 female, 38 were P53 mutated and 27 wild type. Most patients (63 of 66) in IRE cohort were HPV negative. Normalized TCGA HNSCC gene expression and miRNA expression data were obtained from Broad Institute TCGA Genome Data Analysis Center (http://gdac.broadinstitute.org/). mRNA expression data from IRE cohort used in this study has been deposited to NCBI’s Gene Expression Omnibus and is accessible through GEO series accession number GSE107591. In order to inference about potential molecular modulation of TMPRSS2, we also included miRNAs expression for the 66 IRE cohort matched tumor and normal samples from Agilent platform. DNA methylation data for TCGA tumors were obtained from Wanderer (http://maplab.imppc.org/wanderer/). We used miRWalk and miRNet web tools for miRNA-target interaction prediction and pathway enrichment analysis. The correlation and regression analyses as well as the miRNA and gene modulation and the survival analysis were conducted using Matlab R2019.ResultsTMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues and had a prognostic value in HNSCC patients. Reduction of TMPRSS2 expression was more evident in women than in men, in TP53 mutated versus wild TP53 tumors as well as in HPV negative patients compared to HPV positive counterparts. Functionally, we assessed the multivariate effect on TMPRSS2 in a single regression model. We observed that all variables had an independent effect on TMPRSS2 in HNSCC patients with HPV negative, TP53 mutated status and with elevated TP53-dependent Myc-target genes associated with low TMPRSS2 expression. Investigation of the molecular modulation of TMPRSS2 in both HNSCC and lung cancers revealed that expression of microRNAs targeting TMPRSS2 anti-correlated in both TCGA and IRE HNSCC datasets, while there was not evidence of TMPRSS2 promoter methylation in both tumor cohorts. Interestingly, the anti-correlation between microRNAs and TMPRSS2 expression was corroborated by testing this association in a SARS-CoV-2 positive HNSCC patient.ConclusionsCollectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. The protective mechanism might occur, at least partially, through the aberrant activation of TMPRSS2 targeting microRNAs; thereby providing strong evidence on the role of non-coding RNA molecule in host viral infection. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.