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Various biophysical techniques have been extensively employed to study protein aggregation due to its significance. Traditionally, these methods detect aggregation at micrometer length scales and micromolar concentrations. However, unlike in vitro, protein aggregation typically occurs at nanomolar concentrations in vivo. Here, using fluorescence correlation spectroscopy (FCS), we captured bromelain aggregation at concentrations as low as ~20 nM, surpassing the detection limit of traditional methods like thioflavin T fluorescence, scattering, and fluorescence microscopy by more than one order of magnitude. Moreover, using thioflavin T fluorescence‐based FCS, we have detected larger aggregates at higher bromelain concentrations, which is undetectable in FCS otherwise. Importantly, our study reveals inherent heterogeneity in bromelain aggregation, inaccessible to ensemble‐averaged techniques. The presented report may provide a platform for the characterization of premature aggregates at very low protein concentrations, which are thought to be functionally significant species in protein aggregation‐induced diseases. [ABSTRACT FROM AUTHOR]

Electron spin resonance (ESR) or electron paramagnetic resonance (EPR) spectroscopy is an incisive technique for the characterization of paramagnetic centers in inorganic, bioinorganic, and organic molecules and materials. These measurements are enabled with the help of paramagnetic species, such as organic free radicals and ions, electronically excited states, and metal-ligand compounds, some of which with biological importance. In this experiment, analogues of histidine-copper coordination compounds are investigated to show students how ESR line shapes depend on the complexed copper ion electronic structure as well as how the spectral features elucidate the coordination environment of copper. These coordinated compounds play an important role in metal ion coordination in proteins and peptides. The experiment has two parts. First, three copper-imidazole complexes that mimic copper-histidine compounds in the human body are synthesized. Second, the ESR spectrum of each complex is obtained at 77 K from frozen chloroform/methanol and acetonitrile/methanol matrixes and used to elucidate the ligand arrangement of the Cu[superscript 2+] ion and the effect on the unpaired electron density.

This paper aims to understand the changing dynamics of internal labour market segmentation intertwined with the history of working-class struggle in an industrial belt in India's National Capital Region (NCR). Nuances of workers' class struggle in the automobile sector in Delhi-NCR over the last 15 years have shown that unity between permanent and contract workers was key to several successful struggles against worsening work conditions and management control within the global value chains of automobile production. Our fieldwork findings, along with direct and indirect political engagement in the region, reveal that increasing salaries and allotment of supervisory roles to small sections of permanent workers, coupled with the simultaneous fragmentation a lower strata of workers into multiple categories with very low salaries, benefits and heavy workloads, have been significant attempts by capital to break class solidarity among different sections of workers. Relatively pro-labour legislation and trade unions tend to concentrate in high-wage zones, while low-wage and precarious employment remains unprotected by such institutional mechanisms. Labour segmentation is inherent to capitalist exploitation, guarded by institutional mechanisms. Advanced mechanisation reduces distinction of skill requirements between highly paid permanent and lowly paid contract workers. In this context, labour segmentation is a political response to trade unionism from the side of capitalist management. [ABSTRACT FROM AUTHOR]

Among benign neoplasms of the salivary gland, malignancies are less common. One of the rarest tumours found in the oral cavity is oncocytoma, comprising less than 2% of all oral neoplasms and carrying a 1% risk of malignant transformation. Oncocytoma is rare among benign neoplasms, typically affecting females and impacting the major salivary glands. Literature discussing the cytodiagnosis of oncocytoma through Fine Needle Aspiration Cytology (FNAC) is even scarcer. Cytomorphological features indicating a predominantly oncocytic population with benign nuclear characteristics suggest the diagnosis of oncocytoma. The presence of oncocytes alongside other cell types in cytology smears suggests oncocytosis or a tumour-like presentation of Warthin's tumour. Due to its unique features and clinical presentation, clinicians may misdiagnose this tumour as pleomorphic adenoma, haemangioma, or another form of oncocytosis due to its rarity and clinical features. Therefore, only histopathological examination can provide a definitive diagnosis. The present report discusses two unusual cytodiagnoses of oncocytoma identified through FNAC of the parotid gland in a 50-year-old female and a 70-year-old male, along with their clinicoradiological findings and subsequent tumour excision. Furthermore, the authors aim to raise awareness about the importance of a comprehensive work-up and optimal treatment selection for these lesions. [ABSTRACT FROM AUTHOR]

In recent years, there has been phenomenal growth in internet usage worldwide, with a substantial proportion of children and adolescents actively engaging with online platforms. While the internet presents numerous opportunities for children and adolescents, the lack of digital literacy and adequate online safety measures exposes them to various cybercrimes, including cyberbullying, cyberstalking, identity theft, and sexual predation. Moreover, there is growing concern regarding internet addiction among this population. To investigate the determinants of internet addiction among adolescents, we conducted a cross-sectional study in peri-urban Delhi-NCR, India. We used a self-administered questionnaire to gather information on internet usage, and 630 adolescents aged 13–18 participated in the study, also completing an Internet Addiction Test. The findings indicate that 415 adolescents (65.9 %) exhibited no signs of internet addiction, suggesting a healthy relationship with the internet. However, 215 adolescents (33.1 %) displayed symptoms of internet addiction. Among those exhibiting internet addictions, 159 (74.0 %) were classified as mild internet addicts, indicating moderate levels of internet usage. Furthermore, 56 (26.0 %) adolescents were classified as moderate internet addicts, reflecting a higher level of internet addiction. Our study highlights the significant influence of various factors, including family dynamics, environmental factors, and personal experiences, on internet addiction among adolescents. Based on these findings, we propose implementing measures at different levels to foster responsible internet use among adolescents, thereby substantially reducing internet addiction. [ABSTRACT FROM AUTHOR]

There is a pressing need to identify recent directions in the field of aptamer-based sensing. DNA aptamers that are synthetically generated by in vitro selection mechanisms using the SELEX technique are single-stranded oligonucleotides which are selected to bind to a target with favorable sensitivity and selectivity. These aptamers have attracted significant attention due to their high binding affinity and ability to be easily engineered and provide various detection modes in what are known as aptasensors. Our aim is to focus on specialized detection strategies that have gained less attention but are of vital importance, such as optical detection in live cells, fluorescence polarization sensing, multi-analyte detection, colorimetric bioassays, wavelength shifting, and electrochemical-based detection. This will provide us with a perspective to facilitate developments in aptasensor technology for various targets, promising a bright future for biological receptors in the field of biosensing. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most common malignant tumour and the leading cause of cancer-related death in women is breast cancer. The Immunohistochemistry (IHC) method utilised antigens and antibodies to interact to identify cellular or tissue constituents (antigens). This research has been employed as a diagnostic tool for specific cancers. When Programmed Cell Death Ligand 1 (PD-L1) binds to Programmed Cell Death 1 (PD-1), it suppresses the cellular immune response by killing and depleting T-cells. Monoclonal antibodies that block the PD-1/PD-L1 pathway have shown promise as a treatment strategy currently being tested in human cancer trials. Need for the study: Breast cancer is a global issue, and PDL1 expression is emerging as a promising biomarker for breast cancer prognosis. It can provide valuable information treatment planning. Aim: The current study aims to examine the expression of PD-1 and PD-L1 in breast cancer using IHC in all subgroups of breast cancer patients. Both tests can serve as a biomarkers to guide immunotherapeutic interventions, improving prognosis, and correlating with other clinicopathological individual parameters such as age, tumour size, distant metastasis, lymph node involvement, Estrogen Receptor (ER) and Progesterone Receptor (PR) status, Her2neu expression, histological type, and TNM stage. Materials and Methods: This will be a two-year cohort study conducted in the Department of Pathology, Jawaharlal Nehru Medical College (JNMC), Maharashtra, India. The study will include 70 specimens from all cases with a histopathological diagnosis of breast cancer. The Nottingham variant of the Bloom-Richardson Grading System will be used to determine the histological grade of the tumour, and immunostaining for PD-1 and PD-L1 will be performed to evaluate their protein expression. [ABSTRACT FROM AUTHOR]

Identity in south Asia was anchored by, on the one end, community, and on the other, an appreciation of sub-continental (geographical and cultural) space. People, historically, drew their identity as part of communities, which in turn existed in continuity to each-other in the seamless regional expanse of south Asia. Imagination as nationals--a post-colonial construct--faced contestations, both, from community affiliations and spatial imagination contrary to the territorial--modular form of nation-state. As a response, the state fabricated the idea of "patriotic-citizen" and used nationalist historiography to create citizens who are taught to believe the nation as prime-marker of self-definition and act like soldiers, guarding national identity against alternative imaginations. Education has become the most potent devise through which this is achieved. The article, on the basis of textbook narratives in Bangladesh, India and Pakistan, would demonstrate (i) how educational practices build a militarist idea of citizenship and, (ii) in doing so co-opts the demands of community by showing the nation as vindication of community-aspirations and on the other hand erasing conceptualisation of a south Asian space from cognitive maps of its subjects. The idea of "active" citizenship understands "active" as responsible citizenship, emphasising a right based discourse. On the contrary education in south Asia is used to "activate" citizenship which is relational in content--based on ideas of "us" versus "them"--instead of allowing critical understanding of rights and identities.

The chaperone Hsp104, a member of the Hsp100/Clp family of translocases, prevents fibril formation of a variety of amyloidogenic peptides in a paradoxically substoichiometric manner. To understand the mechanism whereby Hsp104 inhibits fibril formation, we probed the interaction of Hsp104 with the Alzheimer's amyloid-ß42 (Aβ42) peptide using a variety of biophysical techniques. Hsp104 is highly effective at suppressing the formation of Thioflavin T (ThT) reactive mature fibrils that are readily observed by atomic force (AFM) and electron (EM) microscopies. Quantitative kinetic analysis and global fitting was performed on serially recorded 1H-15N correlation spectra to monitor the disappearance of Aβ42 monomers during the course of aggregation over a wide range of Hsp104 concentrations. Under the conditions employed (50 µM Aβ42 at 20 ℃), Aβ42 aggregation occurs by a branching mechanism: an irreversible on-pathway leading to mature fibrils that entails primary and secondary nucleation and saturating elongation; and a reversible off-pathway to form nonfibrillar oligomers, unreactive to ThT and too large to be observed directly by NMR, but too small to be visualized by AFM or EM. Hsp104 binds reversibly with nanomolar affinity to sparsely populated Aβ42 nuclei present in nanomolar concentrations, generated by primary and secondary nucleation, thereby completely inhibiting on-pathway fibril formation at substoichiometric ratios of Hsp104 to Aβ42 monomers. Tight binding to sparsely populated nuclei likely constitutes a general mechanism for substoichiometric inhibition of fibrillization by a variety of chaperones. Hsp104 also impacts off-pathway oligomerization but to a much smaller degree initially reducing and then increasing the rate of off-pathway oligomerization. [ABSTRACT FROM AUTHOR]

Translesion synthesis by translesion polymerases is a conserved mechanism of DNA damage tolerance. In bacteria, DinB enzymes are the widely distributed promutagenic translesion polymerases. The role of DinBs in mycobacterial mutagenesis was unclear until recent studies revealed a role for mycobacterial DinB1 in substitution and frameshift mutagenesis, overlapping with that of translesion polymerase DnaE2. Mycobacterium smegmatis encodes two additional DinBs (DinB2 and DinB3) and Mycobacterium tuberculosis encodes DinB2, but the roles of these polymerases in mycobacterial damage tolerance and mutagenesis is unknown. The biochemical properties of DinB2, including facile utilization of ribonucleotides and 8-oxo-guanine, suggest that DinB2 could be a promutagenic polymerase. Here, we examine the effects of DinB2 and DinB3 overexpression in mycobacterial cells. We demonstrate that DinB2 can drive diverse substitution mutations conferring antibiotic resistance. DinB2 induces frameshift mutations in homopolymeric sequences, both in vitro and in vivo. DinB2 switches from less to more mutagenic in the presence of manganese in vitro. This study indicates that DinB2 may contribute to mycobacterial mutagenesis and antibiotic resistance acquisition in combination with DinB1 and DnaE2. [ABSTRACT FROM AUTHOR]

Background Electroconvulsive seizure therapy is often used in both treatment-resistant and geriatric depression. However, preclinical studies identifying targets of chronic electroconvulsive seizure (ECS) are predominantly focused on animal models in young adulthood. Given that putative transcriptional, neurogenic, and neuroplastic mechanisms implicated in the behavioral effects of chronic ECS themselves exhibit age-dependent modulation, it remains unknown whether the molecular and cellular targets of chronic ECS vary with age. Methods We subjected young adult (2–3 months) and middle-aged (12–13 months), male Sprague Dawley rats to sham or chronic ECS and assessed for despair-like behavior, hippocampal gene expression, hippocampal neurogenesis, and neuroplastic changes in the extracellular matrix, reelin, and perineuronal net numbers. Results Chronic ECS reduced despair-like behavior at both ages, accompanied by overlapping and unique changes in activity-dependent and trophic factor gene expression. Although chronic ECS had a similar impact on quiescent neural progenitor numbers at both ages, the eventual increase in hippocampal progenitor proliferation was substantially higher in young adulthood. We noted a decline in reelin⁺ cell numbers following chronic ECS only in young adulthood. In contrast, an age-invariant, robust dissolution of perineuronal net numbers that encapsulate parvalbumin⁺ neurons in the hippocampus were observed following chronic ECS. Conclusion Our findings indicate that age is a key variable in determining the nature of chronic ECS-evoked molecular and cellular changes in the hippocampus. This raises the intriguing possibility that chronic ECS may recruit distinct, as well as overlapping, mechanisms to drive antidepressant-like behavioral changes in an age-dependent manner. [ABSTRACT FROM AUTHOR]

Several global health incidents and evidences show the increasing likelihood of pandemics (large‐scale outbreaks of infectious disease), which has adversely affected all aspects of human lives. It is essential to develop an analytics framework by extracting and incorporating the knowledge of heterogeneous data‐sources to deliver insights for enhancing preparedness to combat the pandemic. Specifically, human mobility, travel history, and other transport statistics have significantly impact on the spread of any infectious disease. This article proposes a spatio‐temporal knowledge mining framework, named STOPPAGE, to model the impact of human mobility and other contextual information over the large geographic areas in different temporal scales. The framework has two key modules: (i) spatio‐temporal data and computing infrastructure using fog/edge based architecture; and (ii) spatio‐temporal data analytics module to efficiently extract knowledge from heterogeneous data sources. We created a pandemic‐knowledge graph to discover correlations among mobility information and disease spread, a deep learning architecture to predict the next hotspot zones. Further, we provide necessary support in home‐health monitoring utilizing Femtolet and fog/edge based solutions. The experimental evaluations on real‐life datasets related to COVID‐19 in India illustrate the efficacy of the proposed methods. STOPPAGE outperforms the existing works and baseline methods in terms of accuracy by ≈$$ \approx $$(18–21)% in predicting hotspots and reduces the power consumption of the smartphone significantly. The scalability study yields that the STOPPAGE framework is flexible enough to analyze a huge amount of spatio‐temporal datasets and reduces the delay in predicting health status compared to the existing studies. [ABSTRACT FROM AUTHOR]