An ESIPT solvatochromic fluorescent and colorimetric probe for sensitive and selective detection of copper ions in environmental samples and cell lines.

Copper is one of the most important transition metals in our body for various physiological functions. An imbalance in the homeostasis of copper in our body can lead to various neurological disorders such as Alzheimer's disease, Parkinson's, and Menkes disease. As a result, there is a need for the detection of excess copper present in the environment and the human system. In this work, we have designed a quinoline-based fluorescent/colorimetric probe (QHS) for rapid and selective detection of copper ions via quenching of fluorescence/color change from yellow to peach which is visible to the naked eye. The probe displayed high selectivity towards copper(II), i.e., Cu(II) in the presence of different metal analytes in water samples. The sensing mechanism of the probe was confirmed by NMR, HRMS, IR spectroscopy, and SEM. The detection limit of Cu(II) ions was found to be 0.493 µM which is lower than the tolerable limit of copper (20 µM) in drinking water as per the EPA. The probe was also utilized for the visualization of Cu(II) in cell lines. The probe was also demonstrated for its application in real-time detection of aqueous samples using portable paper strips.

The role of Drosophila cytidine monophosphate-sialic acid synthetase in the nervous system.

While sialylation plays important functions in the nervous system, the complexity of glycosylation pathways and limitations of genetic approaches preclude the efficient analysis of these functions in mammalian organisms. Drosophila has recently emerged as a promising model for studying neural sialylation. Drosophila sialyltransferase, DSiaT, was shown to be involved in the regulation of neural transmission. However, the sialylation pathway was not investigated in Drosophila beyond the DSiaT-mediated step. Here we focused on the function of Drosophila cytidine monophosphate-sialic acid synthetase (CSAS), the enzyme providing a sugar donor for DSiaT. Our results revealed that the expression of CSAS is tightly regulated and restricted to the CNS throughout development and in adult flies. We generated CSAS mutants and analyzed their phenotypes using behavioral and physiological approaches. Our experiments demonstrated that mutant phenotypes of CSAS are similar to those of DSiaT, including decreased longevity, temperature-induced paralysis, locomotor abnormalities, and defects of neural transmission at neuromuscular junctions. Genetic interactions between CSAS, DSiaT, and voltage-gated channel genes paralytic and seizure were consistent with the hypothesis that CSAS and DSiaT function within the same pathway regulating neural excitability. Intriguingly, these interactions also suggested that CSAS and DSiaT have some additional, independent functions. Moreover, unlike its mammalian counterparts that work in the nucleus, Drosophila CSAS was found to be a glycoprotein-bearing N-glycans and predominantly localized in vivo to the Golgi compartment. Our work provides the first systematic analysis of in vivo functions of a eukaryotic CSAS gene and sheds light on evolutionary relationships among metazoan CSAS proteins.

Development and validation of an electronic version of Sydney Swallow Questionnaire.

BACKGROUND AND AIMS: Accurate assessment of patient-reported oropharyngeal dysphagia (OPD) is essential to guide appropriate management and evaluate response. The Sydney Swallow Questionnaire (SSQ) is a paper-based 17-item inventory developed and validated to objectively detect risk of OPD. An easy-to-use electronic version with digital output has significant potential in streamlining patient assessment. This study aims to develop and validate an electronic version of the SSQ (eSSQ) against the original paper version. METHOD: The English-based paper SSQ was adapted on the online REDcap (Research Electronic Data Capture) platform to be accessible on computer and mobile devices. Patients with OPD and asymptomatic controls completed both electronic and paper versions in randomized order. Patients with stable symptoms then repeated the eSSQ after ≥14 days for test-retest reliability. Paper-based and eSSQs were also collected from an independent cohort for external validation. Agreement of total scores between both versions and eSSQ test-retest reliability were calculated using two-way mixed-effects intra-class correlation coefficient (ICC). RESULTS: 47 dysphagic patients, 32 controls, and 31 patients from an external validation cohort were recruited. The most common underlying etiology was head and neck cancer. Mean eSSQ total score was 789 in dysphagic patients, and 68 in controls. eSSQ had excellent agreement with paper SSQ in total scores among all participants, with ICC 0.97 (95% CI [0.93, 0.98]) in controls, 0.97 (95% CI [0.94, 0.98]) in dysphagic patients and 0.96 (95% CI [0.92, 0.98]) in validation cohort. Test-retest reliability was also excellent (ICC 0.96, 95% CI [0.90, 0.98]). CONCLUSION: The newly developed eSSQ shows excellent agreement with the paper version and test-retest reliability. Future applications of its use may allow for more efficient and accessible patient assessment.

Chemical Modifications of Pyridoxine for Biological Applications: An Overview.

Pyridoxine and its derivatives, pyridoxamine, and pyridoxal have been recognized for more than 70 years and are known for regulating cellular biology and metabolism. During the past few decades, the anti-oxidant and anti-inflammatory properties of pyridoxine and its vitamers were explored. However, an interesting turnabout was observed in pyridoxine chemical modification in the last two decades. The various important pathophysiological aspects of pyridoxine and its derivatives on several cellular systems have been discovered by researchers. Recent findings have shown that many diseases, like cancer, diabetes, hypertension, tuberculosis, epilepsy, and neurodegenerative diseases are linked to the alteration of pyridoxine. Herein, our main focus is to review the importance of pyridoxine and its derivatives obtained by various chemical modifications, in various disease areas and to recognize important directions for future research.

Dysbiosis in Head and Neck Cancer: Determining Optimal Sampling Site for Oral Microbiome Collection.

Recent research suggests that dysbiosis of the oral microbial community is associated with head and neck cancer (HNC). It remains unclear whether this dysbiosis causes chemo-radiotherapy (CRT)-related complications. However, to address this question, it is essential to determine the most representative oral site for microbiome sampling. In this study, our purpose was to determine the optimal site for oral sample collection and whether the presence of HNC is associated with altered oral microbiome from this site. In 21 newly diagnosed HNC patients and 27 healthy controls, microbiome samples were collected from saliva, swabs from buccal mucosa, tongue, hard palate, faucial pillars and all mucosal sites combined. Microbial DNA was extracted and underwent 16S rRNA amplicon gene sequencing. In healthy controls, analysis of observed taxonomic units detected differences in alpha- and beta-diversity between sampling sites. Saliva was found to have the highest intra-community microbial diversity and lowest within-subject (temporal) and between-subject variance. Feature intersection showed that most species were shared between all sites, with saliva demonstrating the most unique species as well as highest overlap with other sites. In HNC patients, saliva was found to have the highest diversity but differences between sites were not statistically significant. Across all sites, HNC patients had lower alpha diversity than healthy controls. Beta-diversity analysis showed HNC patients' microbiome to be compositionally distinct from healthy controls. This pattern was confirmed when the salivary microbiome was considered alone. HNC patients exhibited reduced diversity of the oral microbiome. Salivary samples demonstrate temporal stability, have the richest diversity and are sufficient to detect perturbation due to presence of HNC. Hence, they can be used as representative oral samples for microbiome studies in HNC patients.

Potential Epigenetic Targets for Combating Alzheimer's Disease.

Memory remains an obligatory regime of the human brain, and impaired memory causes serious obstacles in our everyday life. Alzheimer's disease (AD) is one such neurodegenerative disease which mostly affects the elderly population, above the age of 60; marked by cognitive impairment of memory. Besides the known targets of AD against the several etiologies known to date, the zone of epigenetics has recently evolved as an ingenious field in AD. Epigenetic modifications do not affect DNA sequence but only long-term gene expression. Considering the complex multifactorial nature of AD, we herein discuss the various epigenetic targets which might give rise to potential therapeutic approaches. We reviewed the possible epigenetic targets for AD-like HDAC, Sirtuins, glial cells, miRNA and epigenetic modifications like DNA methylation. A deeper insight into these target areas can surely evolve AD diagnosis and therapeutics.

Genetic Interactions Between Drosophila sialyltransferase and ß1,4-N-acetylgalactosaminyltransferase-A Genes Indicate Their Involvement in the Same Pathway.

Sialylated glycans play a prominent role in the Drosophila nervous system where they are involved in the regulation of neural transmission. However, the functional pathway of sialylation in invertebrates, including Drosophila, remains largely unknown. Here we used a combination of genetic and behavioral approaches to shed light on the Drosophila sialylation pathway. We examined genetic interactions between Drosophila sialyltransferase (DSiaT) and ß1,4-N-acetylgalactosaminyltransferase (ß4GalNAcT) genes. Our results indicated that ß4GalNAcTA and DSiaT cooperate within the same functional pathway that regulates neural transmission. We found that ß4GalNAcTA is epistatic to DSiaT. Our data suggest an intriguing possibility that ß4GalNAcTA may participate in the biosynthesis of sialylated glycans.