The DNA mismatch repair (MMR) pathway removes errors that appear during genome replication. MutS is the primary mismatch sensor and forms an asymmetric dimer that encircles DNA to bend it to scan for mismatches. The mechanism utilized to load DNA into the central tunnel was unknown and the origin of the force required to bend DNA was unclear. We show that, in absence of DNA, MutS forms a symmetric dimer wherein a gap exists between the monomers through which DNA can enter the central tunnel.
Rhabdomyosarcoma (RMS) is a predominantly pediatric soft-tissue cancer where the tumor cells exhibit characteristics of the developing skeletal muscle, and the two most common sub-types are embryonal and alveolar RMS. Elevated activation of the receptor tyrosine kinase (RTK) MET is frequent in RMS and is thought to cause increased tumor metastasis and lack of differentiation. However, the reasons underlying dysregulated MET expression and activation in RMS are not well understood. Therefore, we explored the role of Sprouty 2 (SPRY2), a modulator of RTK signaling, in regulating MET.
Deposition of pre-synaptic protein α-synuclein in Lewy bodies and Lewy neurites in the substantia nigra region of brain has been linked with the clinical symptoms of the Parkinson’s disease (PD). Proteotoxic stress conditions and mutations that cause abnormal aggregation of α-synuclein have close association with onset of PD and its progression. Therefore, studies pertaining to α-synuclein mutations play important roles in mechanistic understanding of aggregation behaviour of the protein and subsequent pathology.
α-Synuclein, a major constituent of proteinaceous inclusions named Lewy body, has been shown to be released and taken up by cells, which may facilitate its progressive pathological spreading and neuronal cell death in Parkinson’s disease. However, the pathophysiological effect and signalling cascade initiated by extracellular α-synuclein in cellular milieu are not well understood. Herein we have investigated the perturbations induced by low molecular weight α-synuclein and different types of α-synuclein oligomers in the neuroblastoma SH-SY5Y cells.
New small N-hydroxysuccinimide (NHS)-aryl azide based heterobifunctional crosslinkers have been used as a ‘proof-of-concept’ to crosslink Lysozyme, in a two-step protocol, involving an initial incubation step followed by photolysis (366 nm, 6W lamp). This was further subjected to SDS-PAGE, excision of the ‘dimeric’ band, trypsin digestion and analyzed by ESI-MS and StavroX 3.6.0.1, a bioinformatics software especially suited for identifying intermolecular crosslinks.
Aryl azides are considered as “green” reagents as most of their reactions involve only a benign loss of nitrogen. On the other hand, in the ‘Click’ reaction all the three nitrogen atoms are retained. Aryl azides are very reactive and many short lived intermediates are generated by both thermal and photochemical decomposition of aryl azides. Aryl nitrenes lead to a myriad of possible intermediates yielding products often accompanied by tarry products making it challenging to isolate and purify the products.
Plant-pathogen interactions are constant warfare where in most cases the counter-evolution of the latter is more rapid than the invaded plant-kind. This causes most biotechnological approaches including engineered transgenic plants to fail in their defense sustainability. Recent advances in understanding of functions of pathogenic effectors have greatly highlighted this phenomenon. The fundamental role of effectors is to modulate plant defenses and provide advantageous niche for the pathogen colonization, the function termed as virulence.
Dyslexia is a heritable neurodevelopmental disorder characterized by difficulties in reading and writing. In the present collaborative study, a strong correlation was observed between variations in the protocadherin gamma gene cluster and dyslexia in the members of one family. The protocadherins are trans synaptic molecules involved in cell-cell recognition in the human brain especially in the regions important for cognition and learning. The finding is novel since, this gene cluster has never been associated with dyslexia in the past.
The distinct response shown by different phenotypes of macrophages and monocytes under various clinical conditions have put the heterogeneity of these cells into focus of investigation for several diseases. Recently we have described that after engulfing Hb-activated platelets, classical monocytes differentiated into pro-inflammatory phenotypes, which were abundant in the circulation of PNH and SCD patients. Our current study shows that upon engulfment of Hb-activated platelets, monocytes differentiate into M1-macrophages under M1-polarization stimulus (GM-CSF, IFN-γ+LPS).
