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Reversible enzymatic methylation of mammalian mRNA is widespread and serves crucial regulatory functions, but little is known to what degree chemical alkylators mediate overlapping modifications and whether cells distinguish aberrant from canonical methylations.
Here we use quantitative mass spectrometry to determine the fate of chemically induced methylbases in the mRNA of human cells. Concomitant alteration in the mRNA binding proteome was analyzed by SILAC mass spectrometry.
MMS induced prominent direct mRNA methylations that were chemically identical to endogenous methylbases. Transient loss of 40S ribosomal proteins from isolated mRNA suggests that aberrant methylbases mediate arrested translational initiation and potentially also no-go decay of the affected mRNA. Four proteins (ASCC3, YTHDC2, TRIM25 and GEMIN5) displayed increased mRNA binding after MMS treatment. ASCC3 is a binding partner of the DNA/RNA demethylase ALKBH3 and was recently shown to promote disassembly of collided ribosomes as part of the ribosome quality control (RQC) trigger complex. We find that ASCC3-deficient cells display delayed removal of MMS-induced 1-methyladenosine (m
A) and 3-methylcytosine (m
C) from mRNA and impaired formation of MMS-induced P-bodies.
Our findings conform to a model in which ASCC3-mediated disassembly of collided ribosomes allows demethylation of aberrant m
A and m
C by ALKBH3. Our findings constitute first evidence of selective sanitation of aberrant mRNA methylbases over their endogenous counterparts and warrant further studies on RNA-mediated effects of chemical alkylators commonly used in the clinic.
Our findings conform to a model in which ASCC3-mediated disassembly of collided ribosomes allows demethylation of aberrant m1A and m3C by ALKBH3. Our findings constitute first evidence of selective sanitation of aberrant mRNA methylbases over their endogenous counterparts and warrant further studies on RNA-mediated effects of chemical alkylators commonly used in the clinic.
Nutritional inequality in India has been estimated typically using stunting, wasting and underweight separately which hide the overall magnitude and severity of undernutrition. We used the Composite Index of Anthropometric Failure (CIAF) that combines all three forms of anthropometric failures to assess the severity of undernutrition and identify the most vulnerable social groups and geographical hotspots.
CIAF was constructed using child anthropometric data from the fourth round of the National Family Health Survey (NFHS-4, 2015-16). We considered 24 intersecting sub-groups based on intersections across four main axes of inequality i.e., caste [Scheduled Tribe (ST), Scheduled Caste (SC) and Other], economic position (poor and non-poor), place of residence (rural and urban) and gender (male and female) (eg. ST-Poor-Rural-Female). Cross-tabulation and logistic regression were done to assess the odds of CIAF among intersecting groups and to identify the most vulnerable sub-groups. Concentration curve was pldentified across four geographic clusters.
The study shows social and eco-geographical clustering of multi-dimensional anthropometric failures and indicates the need for focused nutritional interventions among SC and ST community in general and ST children from the poor households. Furthermore, governance interventions that target entire regions across districts and states combined with decentralised planning are needed.
The study shows social and eco-geographical clustering of multi-dimensional anthropometric failures and indicates the need for focused nutritional interventions among SC and ST community in general and ST children from the poor households. Furthermore, governance interventions that target entire regions across districts and states combined with decentralised planning are needed.
Transfemoral amputation is a serious intervention that alters the locomotion pattern, leading to secondary disorders and reduced quality of life. The outcomes of current gait rehabilitation for TFAs seem to be highly dependent on factors such as the duration and intensity of the treatment and the age or etiology of the patient. Although the use of robotic assistance for prosthetic gait rehabilitation has been limited, robotic technologies have demonstrated positive rehabilitative effects for other mobility disorders and may thus offer a promising solution for the restoration of healthy gait in TFAs. This study therefore explored the feasibility of using a bilateral powered hip orthosis (APO) to train the gait of community-ambulating TFAs and the effects on their walking abilities.
Seven participants (46-71years old with different mobility levels) were included in the study and assigned to one of two groups (namely Symmetry and Speed groups) according to their prosthesis type, mobility level, and prior exponstrated as a feasible strategy to train TFAs in a rehabilitation setting. Subjects improved their walking abilities, although further studies are required to evaluate the effectiveness of the APO compared to other gait interventions. Future protocols will include a lighter version of the APO along with optimized assistive strategies.
This study presents the first pilot study to apply a wearable robotic orthosis (APO) to assist TFAs in an overground gait rehabilitation program. The proposed APO-assisted training program was demonstrated as a feasible strategy to train TFAs in a rehabilitation setting. Subjects improved their walking abilities, although further studies are required to evaluate the effectiveness of the APO compared to other gait interventions. Future protocols will include a lighter version of the APO along with optimized assistive strategies.
Recognition of temporomandibular joint (TMJ) involvement in children with juvenile idiopathic arthritis (JIA) has gained increasing attention in the past decade. The clinical assessment of mandibular range of motion characteristics is part of the recommended variables to detect TMJ involvement in children with JIA. The aim of this study was to explore explanatory variables for mandibular range of motion outcomes in children with JIA, with and without clinically established TMJ involvement, and in healthy children.
This cross-sectional study included children with JIA and healthy children of age 6-18 years. Mandibular range of motion variables included active and passive maximum interincisal opening (AMIO and PMIO), protrusion, laterotrusion, dental midline shift in AMIO and in protrusion. STO-609 supplier Additionally, the TMJ screening protocol and palpation pain were assessed. Adjusted linear regression analyses of AMIO, PMIO, protrusion, and laterotrusion were performed to evaluate the explanatory factors. Two adjusted models were constructed model 1 to compare children with JIA and healthy children, and model 2 to compare children with JIA with and without TMJ involvement.
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