Reduction of RAD23A extends lifespan and mitigates pathology in TDP-43 mice.

Protein misfolding and aggregation are cardinal features of neurodegenerative disease (NDD) and they contribute to pathophysiology by both loss-of-function (LOF) and gain-of-function (GOF) mechanisms. This is well exemplified by TDP-43 which aggregates and mislocalizes in several NDDs. The depletion of nuclear TDP-43 leads to reduction in its normal function in RNA metabolism and the cytoplasmic accumulation of TDP-43 leads to aberrant protein homeostasis.

A review on value-addition to plastic waste towards achieving a circular economy.

Plastic and mixed plastic waste (PW) has received increased worldwide attention owing to its huge rate of production, high persistency in the environment, and unsustainable waste management practices. Therefore, sustainable PW management and upcycling approaches are imperative to achieve the objectives of the United Nations Sustainable Development Goals. Numerous recent studies have shown the application and feasibility of various PW conversion techniques to produce materials with better economic value.

The chromatin remodelling factor Chd7 protects auditory neurons and sensory hair cells from stress-induced degeneration.

Neurons and sensory cells are particularly vulnerable to oxidative stress due to their high oxygen demand during stimulus perception and transmission. The mechanisms that protect them from stress-induced death and degeneration remain elusive. Here we show that embryonic deletion of the chromodomain helicase DNA-binding protein 7 (CHD7) in auditory neurons or hair cells leads to sensorineural hearing loss due to postnatal degeneration of both cell types.

Potential Chemicals from Plastic Wastes.

Plastic is referred to as a "material of every application". From the packaging and automotive industries to the medical apparatus and computer electronics sectors, plastic materials are fulfilling demands efficiently. These plastics usually end up in landfills and incinerators, creating plastic waste pollution.

is required for axial elongation and segmentation in vertebrate embryos.

During vertebrate embryonic development, the formation of axial structures is driven by a population of stem-like cells that reside in a region of the tailbud called the chordoneural hinge (CNH). We have compared the mouse CNH transcriptome with those of surrounding tissues and shown that the CNH and tailbud mesoderm are transcriptionally similar, and distinct from the presomitic mesoderm. Amongst CNH-enriched genes are several that are required for axial elongation, including , , and , and androgen/oestrogen receptor nuclear signalling components such as We show that the pattern and duration of tailbud expression is conserved in mouse, zebrafish and chicken embryos, and that is required for axial elongation and somitogenesis in zebrafish embryos.

PRDM1 controls the sequential activation of neural, neural crest and sensory progenitor determinants.

During early embryogenesis, the ectoderm is rapidly subdivided into neural, neural crest and sensory progenitors. How the onset of lineage determinants and the loss of pluripotency markers are temporally and spatially coordinated is still debated. Here, we identify a crucial role for the transcription factor PRDM1 in the orderly transition from epiblast to defined neural lineages in chick.

Neural induction by the node and placode induction by head mesoderm share an initial state resembling neural plate border and ES cells.

Around the time of gastrulation in higher vertebrate embryos, inductive interactions direct cells to form central nervous system (neural plate) or sensory placodes. Grafts of different tissues into the periphery of a chicken embryo elicit different responses: Hensen's node induces a neural plate whereas the head mesoderm induces placodes. How different are these processes? Transcriptome analysis in time course reveals that both processes start by induction of a common set of genes, which later diverge.

Cell interactions, signals and transcriptional hierarchy governing placode progenitor induction.

In vertebrates, cranial placodes contribute to all sense organs and sensory ganglia and arise from a common pool of Six1/Eya2+ progenitors. Here we dissect the events that specify ectodermal cells as placode progenitors using newly identified genes upstream of the Six/Eya complex. We show in chick that two different tissues, namely the lateral head mesoderm and the prechordal mesendoderm, gradually induce placode progenitors: cells pass through successive transcriptional states, each identified by distinct factors and controlled by different signals.

Effect of signal peptide on stability and folding of Escherichia coli thioredoxin.

The signal peptide plays a key role in targeting and membrane insertion of secretory and membrane proteins in both prokaryotes and eukaryotes. In E. coli, recombinant proteins can be targeted to the periplasmic space by fusing naturally occurring signal sequences to their N-terminus.

Identification and thermodynamic characterization of molten globule states of periplasmic binding proteins.

Molten globule-like intermediates have been shown to occur during protein folding and are thought to be involved in protein translocation and membrane insertion. However, the determinants of molten globule stability and the extent of specific packing in molten globules is currently unclear. Using far- and near-UV CD and intrinsic and ANS fluorescence, we show that four periplasmic binding proteins (LBP, LIVBP, MBP, and RBP) form molten globules at acidic pH values ranging from 3.

Contribution of cation-pi interactions to protein stability.

Calculations predict that cation- interactions make an important contribution to protein stability. While there have been some attempts to experimentally measure strengths of cation-pi interactions using peptide model systems, much less experimental data are available for globular proteins. We have attempted to determine the magnitude of cation-pi interactions of Lys with aromatic amino acids in four different proteins (LIVBP, MBP, RBP, and Trx).

Thermodynamic effects of proline introduction on protein stability.

The amino acid Pro is more rigid than other naturally occurring amino acids and, in proteins, lacks an amide hydrogen. To understand the structural and thermodynamic effects of Pro substitutions, it was introduced at 13 different positions in four different proteins, leucine-isoleucine-valine binding protein, maltose binding protein, ribose binding protein, and thioredoxin. Three of the maltose binding protein mutants were characterized by X-ray crystallography to confirm that no structural changes had occurred upon mutation.

Protein stabilization by introduction of cross-strand disulfides.

Disulfides cross-link residues in a protein that are separated in primary sequence and stabilize the protein through entropic destabilization of the unfolded state. While the removal of naturally occurring disulfides leads to protein destabilization, introduction of engineered disulfides does not always lead to significant stabilization of a protein. We have analyzed naturally occurring disulfides that span adjacent antiparallel strands of beta sheets (cross-strand disulfides).