Deep Phosphoproteome Landscape of Interhemispheric Functionality of Neuroanatomical Regions of the Human Brain.

Post-translational modifications (PTMs) are one of the compulsive and predominant biological processes that regulate the diverse molecular mechanism, modulate the onset of disease, and are the reason behind the functional diversity of proteins. Despite the widespread research findings in neuroproteomics, one of the key drawbacks has been the lack of proteome-level knowledge of hemispheric lateralization. We have investigated the proteome level expression in different neuroanatomical regions under the Human Brain Proteome Project (HBPP) and developed the global interhemispheric brain proteome map (Brainprot) earlier. Furthermore, this study has extended to decipher the phosphoproteome map of human brain interhemispheric regions through high-resolution mass spectrometry. The phosphoproteomics examination of 12 unique interhemispheric neurological brain regions using Orbitrap fusion liquid chromatography with tandem mass spectrometry provided comprehensive coverage of 996 phosphoproteins, 2010 phosphopeptides, and 3567 phosphosites. Moreover, interhemispheric phosphoproteome profiling has been categorized according to synaptic ontologies and interhemispheric expression to understand the functionality. Finally, we have integrated the phosphosites data under the PhosphoMap section in the Inter-Hemispheric Brain Proteome Map Portal (https://www.brainprot.org/) for the advancement and support of the ongoing neuroproteomics research worldwide. Data is available via ProteomeXchange with the identifier PXD031188.

Mass spectrometry based protein biomarkers and drug target discovery and clinical diagnosis in Age-Related progressing neurodegenerative diseases.

Neurodegenerative diseases correspond to overly complex health disorders that are driven by intersecting pathophysiology that are often trapped in vicious cycles of degeneration and cognitive decline. The usual diagnostic route of these diseases is based on postmortem examination that involves identifying pathology that is specific to the disease in the brain. However, in such cases, accurate diagnosis of the specific disease is limited because clinical disease presentations are often complex that do not easily allow to discriminate patient's cognitive, behavioral, and functional impairment profiles. Additionally, an early identification and therapeutic intervention of these diseases is pivotal to slow the progression of neurodegeneration and extend healthy life span. Mass spectrometry-based techniques have proven to be hugely promising in biological sample analysis and discovery of biomarkers including protein and peptide biomarkers for potential drug target discovery. Recent studies on these biomarkers have demonstrated their potential for applications in early diagnostics and identifying therapeutic targets to battle against neurodegenerative diseases. In this review, we have presented principles of mass spectrometry (MS) and the associated workflows in analyzing and imaging biological samples for discovery of biomarkers. We have especially focused on age-related progressing neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) and the related MS-based biomarker developments for these diseases. Finally, we present a future perspective discussing the potential research directions ahead.

DNA Knot Malleability in Single-Digit Nanopores.

Knots in long DNA molecules are prevalent in biological systems and serve as a model system for investigating static and dynamic properties of biopolymers. We explore the dynamics of knots in double-stranded DNA in a new regime of nanometer-scale confinement, large forces, and short time scales, using solid-state nanopores. We show that DNA knots undergo isomorphic translocation through a nanopore, retaining their equilibrium morphology by swiftly compressing in a lateral direction to fit the constriction. We observe no evidence of knot tightening or jamming, even for single-digit nanopores. We explain the observations as the malleability of DNA, characterized by sharp buckling of the DNA in nanopores, driven by the transient disruption of base pairing. Our molecular dynamics simulations support the model. These results are relevant not only for the understanding of DNA packing and manipulation in living cells but also for the polymer physics of DNA and the development of nanopore-based sequencing technologies.

Complex DNA knots detected with a nanopore sensor.

Equilibrium knots are common in biological polymers-their prevalence, size distribution, structure, and dynamics have been extensively studied, with implications to fundamental biological processes and DNA sequencing technologies. Nanopore microscopy is a high-throughput single-molecule technique capable of detecting the shape of biopolymers, including DNA knots. Here we demonstrate nanopore sensors that map the equilibrium structure of DNA knots, without spurious knot tightening and sliding. We show the occurrence of both tight and loose knots, reconciling previous contradictory results from different experimental techniques. We evidence the occurrence of two quantitatively different modes of knot translocation through the nanopores, involving very different tension forces. With large statistics, we explore the complex knots and, for the first time, reveal the existence of rare composite knots. We use parametrized complexity, in concert with simulations, to test the theoretical assumptions of the models, further asserting the relevance of nanopores in future investigation of knots.

Phenothiazine-Based D-A-π-A Dyes for Highly Efficient Dye-Sensitized Solar Cells: Effect of Internal Acceptor and Non-Conjugated π-Spacer on Device Performance.

Three new D-A-π-A metal-free organic dyes based on phenothiazine as a donor (D) and non-conjugated π-spacer were designed and synthesized. The incorporation of different 'internal acceptors' (electron traps) such as benzothiadiazole (BTD), benzotriazole (BTA), and pyridine were shown to allow systematic tuning of the energy levels and the photophysical properties. The AI-1 dye showed lower electronic disorder compared with the other two dyes. The efficiencies achieved with AI-1, AI-2, and AI-3 dyes were 8.5 % (Jsc =15.42 mA cm-2 , Voc =0.78 V, FF=68 %), 7 % (Jsc =12.8 mA cm-2 , Voc =0.78 V, FF=68 %) and 6.7 % (Jsc =11.57 mA cm-2 , Voc =0.82 V, FF=68.26 %), respectively. The incorporation of non-conjugated phenothiazine as a π-spacer in D-A-π-A dyes showed remarkable enhancement in the photovoltaic performance of dye-sensitized solar cell (DSSC) devices. The sealed DSSC devices with iodide/tri-iodide (I- /I3 - )-based liquid electrolyte showed promising stability under ambient conditions.

Pt- and TCO-Free Flexible Cathode for DSSC from Highly Conducting and Flexible PEDOT Paper Prepared via in Situ Interfacial Polymerization.

Here, we report the preparation of a flexible, free-standing, Pt- and TCO-free counter electrode in dye-sensitized solar cell (DSSC)-derived from polyethylenedioxythiophene (PEDOT)-impregnated cellulose paper. The synthetic strategy of making the thin flexible PEDOT paper is simple and scalable, which can be achieved via in situ polymerization all through a roll coating technique. The very low sheet resistance (4 Ω/□) obtained from a film of 40 µm thick PEDOT paper (PEDOT-p-5) is found to be superior to the conventional fluorine-doped tin oxide (FTO) substrate. The high conductivity (357 S/cm) displayed by PEDOT-p-5 is observed to be stable under ambient conditions as well as flexible and bending conditions. With all of these features in place, we could develop an efficient Pt- and TCO-free flexible counter electrode from PEDOT-p-5 for DSSC applications. The catalytic activity toward the tri-iodide reduction of the flexible electrode is analyzed by adopting various electrochemical methodologies. PEDOT-p-5 is found to display higher exchange current density (7.12 mA/cm(2)) and low charge transfer resistance (4.6 Ω) compared to the benchmark Pt-coated FTO glass (2.40 mA/cm(2) and 9.4 Ω, respectively). Further, a DSSC fabricated using PEDOT-p-5 as the counter electrode displays a comparable efficiency of 6.1% relative to 6.9% delivered by a system based on Pt/FTO as the counter electrode.