Assemble-Disassemble-Reassemble Dynamics in Copper Nanocluster-Based Superstructures.

Assembling metal nanoclusters (MNCs) to form superstructures generates exciting photophysical properties distinct from those of their discrete precursors. Controlling the assembly process of MNCs and understanding the assembly-disassembly dynamics can have implications in achieving the reversible self-assembly of MNCs. The formation of self-assembled copper nanoclusters (CuNCs) as homogeneous superstructures and the underlying mechanisms governing such a process remain unexplored. Smart molecular imprinting of surface ligands can establish the forces necessary for the formation of such superstructures. Herein, we report highly luminescent, ordered superstructures of 4-phenylimidazole-2-thiol (4-PIT)-protected CuNCs with the help of l-ascorbic acid as a secondary ligand. Through a comprehensive spectroscopic analysis, we deciphered the mechanism of the self-assembly process, where the role of interligand H-bonding and C-H-π interactions was established. Notably, efficient reversibility of assembly-disassembly was demonstrated by re-establishing the interligand interactions and regenerating their photophysical and morphological signatures.

Deciphering the liquid-liquid phase separation induced modulation in the structure, dynamics, and enzymatic activity of an ordered protein ß-lactoglobulin.

Owing to the significant role in the subcellular organization of biomolecules, physiology, and the realm of biomimetic materials, studies related to biomolecular condensates formed through liquid-liquid phase separation (LLPS) have emerged as a growing area of research. Despite valuable contributions of prior research, there is untapped potential in exploring the influence of phase separation on the conformational dynamics and enzymatic activities of native proteins. Herein, we investigate the LLPS of ß-lactoglobulin (ß-LG), a non-intrinsically disordered protein, under crowded conditions. In-depth characterization through spectroscopic and microscopic techniques revealed the formation of dynamic liquid-like droplets, distinct from protein aggregates, driven by hydrophobic interactions. Our analyses revealed that phase separation can alter structural flexibility and photophysical properties. Importantly, the phase-separated ß-LG exhibited efficient enzymatic activity as an esterase; a characteristic seemingly exclusive to ß-LG droplets. The droplets acted as robust catalytic crucibles, providing an ideal environment for efficient ester hydrolysis. Further investigation into the catalytic mechanism suggested the involvement of specific amino acid residues, rather than general acid or base catalysis. Also, the alteration in conformational distribution caused by phase separation unveils the latent functionality. Our study delineates the understanding of protein phase separation and insights into the diverse catalytic strategies employed by proteins. It opens exciting possibilities for designing functional artificial compartments based on phase-separated biomolecules.

Fluorescence Resonance Energy Transfer in a Supramolecular Assembly of Luminescent Silver Nanoclusters and a Cucurbit[8]uril-Based Host-Guest System.

The understanding of interactions between organic chromophores and biocompatible luminescent noble metal nanoclusters (NCs) leading to an energy transfer process that has applications in light-harvesting materials is still in its nascent stage. This work describes a photoluminescent supramolecular assembly, made in two stages, employing an energy transfer process between silver (Ag) NCs as the donor and a host-guest system as the acceptor that can find potential applications in diverse fields. Initially, we explored the host-guest chemistry between a cationic guest ethidium bromide and cucurbit[8]uril host to modulate the fluorescence property of the acceptor. The host-guest interactions were characterized by using UV-vis absorption, steady-state and time-resolved spectroscopy, molecular docking, proton 1H nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and isothermal calorimetry studies. Next, we prepared a series of blue-emitting AgNCs using different templates such as proteins and peptides. We have found that these AgNCs can be employed as a donor in the energy transfer process upon mixing with the above acceptor for emission color tuning. Our in-depth studies also revealed that surface ligands could play a key role in modulating the energy transfer efficiency. Overall, by employing a noncovalent strategy, we have tried to develop Förster resonance energy transfer (FRET) pairs using blue-emitting NCs and a host-guest complex that could find potential applications in constructing advanced sustainable light-harvesting, white light-emitting, and anti-counterfeiting materials.

Solvent-Induced Modulation in the Optical Properties of Copper Nanoclusters and Revealing the Isomeric Effect of Templates.

The solvent plays an influential role in controlling the nucleation process of metal nanoclusters (MNCs) and thereby significantly modulates their optical signatures. Herein, we have demonstrated the solvent-induced modulation in the optical properties of copper nanoclusters (CuNCs), primarily governed by the solvent polarity. During the preparation of para-mercaptobenzoic acid (p-MBA)-templated CuNCs, the simultaneous formation of blue-emitting CuNCs (B-CuNCs) and red-emitting CuNCs (R-CuNCs) were observed up to 7 h of reaction time, reflected from the systematic increment in the photoluminescence (PL) intensity at 420 nm and 615 nm, respectively. However, after 7 h of reaction time, the exclusive formation of B-CuNCs was observed. Such simultaneous growth and depletion dynamics of CuNCs result in a significant modulation in their optical properties. The variation of the solvent from water to less polar solvents such as DMSO and DMF restricts this inter-cluster dynamics by stabilizing both the CuNCs (B-CuNCs and R-CuNCs). Thereby, a single-component White Light Emission (WLE) was realized in DMSO with CIE coordinates (0.37, 0.36). The isomeric effect of the templates has also been investigated which extensively controls the optical and catalytic properties of the CuNCs.

Hsc70-4 aggravates PolyQ-mediated neurodegeneration by modulating NF-κB mediated immune response in Drosophila.

Huntington's disease occurs when the stretch of CAG repeats in exon 1 of the huntingtin (htt) gene crosses the permissible limit, causing the mutated protein (mHtt) to form insoluble aggregates or inclusion bodies. These aggregates are non-typically associated with various essential proteins in the cells, thus disrupting cellular homeostasis. The cells try to bring back normalcy by synthesizing evolutionary conserved cellular chaperones, and Hsp70 is one of the families of heat shock proteins that has a significant part in this, which comprises of heat-inducible and cognate forms. Here, we demonstrate that the heat shock cognate (Hsc70) isoform, Hsc70-4/HSPA8, has a distinct role in polyglutamate (PolyQ)-mediated pathogenicity, and its expression is enhanced in the polyQ conditions in Drosophila. Downregulation of hsc70-4 rescues PolyQ pathogenicity with a notable improvement in the ommatidia arrangement and near-normal restoration of optic neurons leading to improvement in phototaxis response. Reduced hsc70-4 also attenuates the augmented immune response by decreasing the expression of NF-κB and the antimicrobial peptides, along with that JNK overactivation is also restored. These lead to the rescue of the photoreceptor cells, indicating a decrease in the caspase activity, thus reverting the PolyQ pathogenicity. At the molecular level, we show the interaction between Hsc70-4, Polyglutamine aggregates, and NF-κB, which may be responsible for the dysregulation of signaling molecules in polyQ conditions. Thus, the present data provides a functional link between Hsc70-4 and NF-κB under polyQ conditions.

Macrocyclic Cavitand ß-Cyclodextrin Inhibits the Alcohol-Induced Trypsin Aggregation.

Trypsin, the most abundant pancreatic protein, aids in protein digestion by hydrolysis and exhibits aggregation propensity in presence of alcohol, which can further lead to pancreatitis and eventually pancreatic cancer. Herein, by several experimental and theoretical approaches, we unearth the inhibition of alcohol-induced aggregation of Trypsin by macrocyclic cavitand, ß-cyclodextrin (ß-CD). ß-CD interacts with the native protein and shows inhibitory effect in a dose dependent manner. Moreover, the secondary structures and morphologies of Trypsin in presence of ß-CD also clearly emphasize the inhibition of fibril formation. From Fluorescence Correlation Spectroscopy, we observed an enhancement in diffusion time of Nile Red with ∼2.5 times increase in hydrodynamic radius, substantiating the presence of fibrillar structure. Trypsin also shows reduction in its functional activity due to alcohol-induced aggregation. Our simulation data reports the probable residues responsible for fibril formation, which was validated by molecular docking studies.

DNA-Templated Modulation in the Photophysical Properties of a Fluorescent Molecular Rotor Auramine O by Varying the DNA Composition.

This work delineates an integrative approach combining spectroscopic and computational studies to decipher the association-induced fluorescence properties of a fluorescent molecular rotor, viz., auramine O (AuO), after interacting with 20-mer duplex DNA having diverse well-matched base pairs. While exploring the scarcely explored sequence-dependent interaction mechanism of AuO and DNA, we observed that DNA could act as a conducive scaffold to the formation of AuO dimer through noncovalent interactions at lower molecular density. The photophysical properties of AuO depend on the nucleotide compositions as described from sequence-dependent shifting in the emission and absorption maxima. Furthermore, we explored such DNA base pair-dependent fluorescence spectral characteristics of AuO toward discriminating the thermodynamically most stable single nucleotide mismatch in a 20-mer sequence. Our results are interesting and could be useful in developing analogues with further enhanced emission properties toward mismatched DNA sequences.

Predictors of spousal coercive control and its association with intimate partner violence evidence from National Family Health Survey-4 (2015-2016) India.

BACKGROUND: The feminist theory posits that spousal coercive control is not random but a purposeful and systematic men's strategy to control and dominate their female partners. The frequency of coercive control is more than emotional, physical, and sexual intimate partner violence (IPV). Coercive control is usually mistaken with psychological abuse when it is not and has recently gained independent attention within the spectrum of IPV. The role of socioeconomic factors in determining coercive control and associations between coercive control and form of IPV is less researched. OBJECTIVE: We aimed to examine sociodemographic and socioeconomic predictors of spousal coercive control and its association with IPV (past 12-months). METHODS: We analysed data of 66,013 ever-married women aged 15-49 from the National Family Health Survey (NFHS)-4 (2015-2016). Estimates involved bivariate and multivariate logistic regression models, and marginal effects prediction. RESULTS: The prevalence of spousal coercive control is more commonly reported by 48% of women than the prevalence of IPV 25% (emotional 11%, physical 22%, and sexual 5%) in the past 12 months. Adjusted odds ratio indicate that women having three and more children (aOR 1.1, 95% CI: 1.0-1.2), women work status (1.1; 1.1-1.2), husband's secondary (1.1; 1.1-1.2) or higher education (1.1; 1.1-1.2), and husband alcohol consumption (1.7; 1.6-1.7) increase the odds of coercive control. In the fully adjusted model coercive control independently increased the likelihood of experiencing emotional (aOR 2.8.; 95% CI: 2.6, 3.1), physical (2.2; 2.1, 2.3), and sexual (2.5; 2.3, 2.8) IPV in the past 12 months; and with an increase in each additional indicator of coercive control acts, the likelihood of physical, sexual, and emotional IPV further increases. When women reported six indicators of coercive control, the predicted proportion of women experiencing emotional 53%, physical 45%, and sexual IPV was 25% in the fully adjusted model. CONCLUSION: Coercive control limits women's social support and contacts contributing to low self-esteem, self-efficacy, and poor mental health. The purpose of this study is to highlight that understudied coercive control is more common than other forms of IPV and is a potential risk factor for physical, sexual, and emotional IPV independently. The inclusion of coercive control in interventions is crucial to prevent form of IPV. Survivals long-term safety and independence can be secured if the current protection law against domestic violence is extended to encompass coercive control.

Tyrosine-Templated Dual-Component Silver Nanomaterials Exhibit Photoluminescence and Versatile Antimicrobial Properties through ROS Generation.

The role of small molecules in the preparation of metal nanomaterials generates considerable interest in the fields from materials science to interdisciplinary sciences. In this study, a small amino acid, l-tyrosine (Tyr), has been used as a ligand precursor for the preparation of silver nanomaterials (AgNMs) comprising a dual system: smaller silver nanoclusters (responsible exclusively for the photophysical properties) and larger silver nanoparticles (responsible exclusively for the antimicrobial properties). The luminescent properties of this AgNM system substantiate the role played by Tyr as a capping and a reducing agent outside the protein environment. An interesting feature of this report is the promising antimicrobial properties of the AgNMs against Saccharomyces cerevisiae, Candida albicans, Escherichia coli, and Bacillus cereus cell lines. The importance of this work is that this investigation demonstrates the combating ability of our AgNM system against pathogenic strains (C. albicans and B. cereus) as well. Moreover, the mechanistic aspects of the antimicrobial activity of the AgNMs were elucidated using various methods, such as propidium iodide staining, monitoring reactive oxygen species generation, leakage of proteins, DNA cleavage, etc. We propose that AgNM-mediated cytotoxicity in S. cerevisiae stems from the generation of singlet oxygen (1O2) species that create oxidative stress, disrupting the cell membrane and thereby resulting in leakage of proteins from the cells. This study can pave the way toward elucidating the role of a small molecule, Tyr, in the formation of NMs and describes the use of new NMs in potential antimicrobial applications.

Challenges for pregnant women seeking institutional care during the COVID-19 lockdown in India: A content analysis of online news reports.

India's nationwide lockdown to curtail the transmission of Covid-19 has given rise to concerns over the health system's response to maternal and child health (MCH) services. This paper aims to understand the challenges faced by pregnant women seeking institutional care during the lockdown. We conducted a qualitative content analysis of 54 online news reports, published in English and Hindi, between 25 March 2020 and 31 May 2020. They covered cases across 17 states in India and 16 maternal deaths. Three broad thematic categories of challenges for pregnant women emerged from the analysis: 1) physical access to health facilities, 2) admission to health facilities, and 3) lack of respectful maternity care during the lockdown. In conclusion, strengthening health systems and incorporating MCH into the Covid-19 response is imperative. Failure to provide quality MCH services during the lockdown has implications for the continuum of women's care, maternal mortality, and human rights.

GinMicrosatDb: a genome-wide microsatellite markers database for sesame (Sesamum indicum L.).

Molecular breeding in sesame is still at infancy due to limited number of microsatellite markers available and the low level of polymorphism exhibited by them. Therefore, whole genome sequencing was used for development of microsatellite markers so as to ensure availability of substantial number of polymorphic markers for use in marker assisted breeding programs. Whole genome sequencing of sesame variety 'Swetha' was done using Illumina paired-end sequencing and Roche 454 shotgun sequencing technologies (GCA_000975565.1 in GenBank). 'GinMicrosatDb', a genome-wide microsatellite marker database has been developed using the whole genome sequence data of sesame variety 'Swetha'. The database consists of microsatellites localized on both linkage groups and scaffolds with their genomic co-ordinates. It provides five sets of forward and reverse primers for each of the microsatellite loci along with the flanking sequences, primer GC content, product size and melting temperature etc. The distribution of microsatellites can be viewed and selected through a genome browser as well as through a physical map. The newly identified microsatellite markers are expected to help sesame breeders in developing marker tags for traits of economic importance thereby bringing about greater efficiency in marker-assisted selection programs.

Spinocerebellar ataxia type 6 in eastern India: Some new observations.

INTRODUCTION: Spinocerebellar ataxias (SCAs) are hereditary, autosomal dominant progressive neurodegenerative disorders showing clinical and genetic heterogeneity. They are usually manifested clinically in the third to fifth decade of life although there is a wide variability in the age of onset. More than 36 different types of SCAs have been reported so far and about half of them are caused by pathological expansion of the trinucleotide, Cytosine Alanine Guanine (CAG) repeat. The global prevalence of SCA is 0.3-2 per 100,000 population, SCA3 being the commonest variety worldwide, accounting for 20-50 per cent of all cases, though SCA 2 is generally considered as the commonest one in India. However, SCA6 has not been addressed adequately from India though it is common in the eastern Asian countries like, Japan, Korea and Thailand. OBJECTIVE: The present study was undertaken to identify the prevalence of SCA6 in the city of Kolkata and the eastern part of India. MATERIALS AND METHODS: 83 consecutive patients were recruited for the study of possible SCAs and their clinical features and genotype were investigated. RESULTS: 6 of the 83 subjects turned out positive for SCA6, constituting therefore, 13.33% of the patient pool. DISCUSSION: SCA6 is prevalent in the eastern part of India, though not as frequent as the other common varieties. CONCLUSIONS: Further community based studies are required in order to understand the magnitude of SCA6 in the eastern part, as well as in other regions of India.

Joseph Godwin Greenfield: The father of neuropathology (1884-1958).

The systematic study of neuropathology was initiated by Godwin Greenfield in the early part of the 20(th) century. He worked at the National Hospital, Queen Square, London for the major period of his life and worked on various subjects like cerebrospinal fluid, intracranial tumours, cerebellar ataxias, dystrophia myotonica, disseminated sclerosis, subacute combined degeneration of the spinal cord, and the like. After his retirement he visited the National Institute of Neurological Diseases and Blindness in Bethesda, Maryland, USA, from time to time and there he died suddenly from myocardial infarction.

Famous people with Tourette's syndrome: Dr. Samuel Johnson (yes) & Wolfgang Amadeus Mozart (may be): Victims of Tourette's syndrome?

Tourette's syndrome is a clinical condition characterized by multiple motor tics and vocal tics which occurs in the age range 5-25 years and the intensity of the symptoms changes with time. It is felt that at least two remarkable personalities namely, Dr. Samuel Johnson from England, a man of letters and the compiler of the first ever English dictionary, and Wolfgang Amadeus Mozart from Austria, one of the greatest musical genius of all time, possibly suffered from this condition. Tourette's syndrome is often described as the classical borderzone between neurology and psychiatry and every neurologist wonders at the curious and fascinating clinical features of this condition. It seems that at least two remarkable personalities, Dr. Samuel Johnson, a man of letters and the first person to compile an English dictionary, and Wolfgang Amadeus Mozart, arguably the most creative musical composer of all time, were possibly afflicted with this condition.

The neuropsychiatric ailment of Vincent Van Gogh.

Vincent Van Gogh is one of the most celebrated creative artists of all time. All his life, he was afflicted by some kind of neurological or psychiatric disorder, which remains a mystery even today. Many historians and his personal physicians believe that he suffered from epilepsy while others felt that he was affected by Ménière's disease. Features such as hypergraphia, atypical sexuality, and viscosity of thinking suggest the possibility of Gastaut-Geschwind phenomenon, a known complication of complex partial seizure. On the contrary, some historians feel that he was forced to sever his right ear in order to get relief from troublesome tinnitus, a complication of Ménière's disease. He was addicted to the liquor absinthe, which is known to lead to xanthopsia, and many authorities argue that this was the reason for his penchant for the deep and bright yellow color in many of his paintings. Others have suggested the possibility of bipolar disorder, sunstroke, acute intermittent porphyria, and digitalis toxicity as well.

Failure of endovascular stenting for popliteal cystic disease.

We describe an attempted endovascular stenting for popliteal artery stenosis secondary to adventitial cystic disease in a 56-year-old man with lifestyle-limiting claudication. Despite technical success, it remained patent only for 1 week, requiring interposition venous graft reconstruction eventually.