Critical Assessment of Micellar Surface Charge-Dependent Disaggregation and Reaggregation of a Bis-Indole Self-Aggregate: What Should Be Our Case-Dependent Choice?

"Aggregation-caused quenching" is a deep-seated mechanism and has been widely used by the researchers as the possible basis for new sensor development. Contrast to aggregation, its turn around process, disaggregation, has gained much less consideration so far. Unfortunately, study of the further scope for reaggregation of the disaggregated probe assembly in the same solution, as and when required, is still under the rare category. The central theme of the current study is focused on this aspect. For this purpose, the effects of headgroup charge (cationic, anionic, and nonionic) and polarity of the micelles on the degree of disaggregation and subsequent emission amelioration of a synthesized bis-indole derivative, 3,3'-bisindolyl(phenyl)methane (BIPM), are studied using steady-state and time-resolved spectroscopic techniques. The relative emission yield of BIPM (φf = 0.01) is significantly enhanced in the presence of cetyltrimethylammonium bromide (φf = 0.21) and polyoxyethylene (20) sorbitan monolaurate (φf = 0.24), whereas comparatively less emission enhancement is recorded within the sodium dodecyl sulfate system (φf = 0.07). In contrast, addition of an external biophilic agent, uric acid, causes requenching of the enhanced emission because of the reaggregation of the disaggregated probes. Detailed microscopic and calorimetric studies are also adopted to investigate the disaggregation-reaggregation mechanism of BIPM associations. The study will provide prior insights about the use of suitable micellar systems for the required degree of disaggregation as well as for the modulation of emission efficiency by controlled tuning of the disaggregation-reaggregation equilibrium for similar probe associations in pure aqueous medium avoiding any chemical transformation.

An Overview of Bacteria-Mediated Heavy Metal Bioremediation Strategies.

Contamination-free groundwater is considered a good source of potable water. Even in the twenty-first century, over 90 percent of the population is reliant on groundwater resources for their lives. Groundwater influences the economical state, industrial development, ecological system, and agricultural and global health conditions worldwide. However, different natural and artificial processes are gradually polluting groundwater and drinking water systems throughout the world. Toxic metalloids are one of the major sources that pollute the water system. In this review work, we have collected and analyzed information on metal-resistant bacteria along with their genetic information and remediation mechanisms of twenty different metal ions [arsenic (As), mercury (Hg), lead (Pb), chromium (Cr), iron (Fe), copper (Cu), cadmium (Cd), palladium (Pd), zinc (Zn), cobalt (Co), antimony (Sb), gold (Au), silver (Ag), platinum (Pt), selenium (Se), manganese (Mn), molybdenum (Mo), nickel (Ni), tungsten (W), and uranium (U)]. We have surveyed the scientific information available on bacteria-mediated bioremediation of various metals and presented the data with responsible genes and proteins that contribute to bioremediation, bioaccumulation, and biosorption mechanisms. Knowledge of the genes responsible and self-defense mechanisms of diverse metal-resistance bacteria would help us to engineer processes involving multi-metal-resistant bacteria that may reduce metal toxicity in the environment.

Hydrogen bond directed high-fidelity optical detection of picric acid: A single driver on diverse roads towards the same destiny.

High-fidelity optical detection of picric acid (PA) is necessary due to its toxic and explosive nature. Moreover, PA is a molecule with versatile features, such as hydrogen bond or proton donor-acceptor centers, extremely low pKa, highly electron-deficient center, high water solubility, etc. These unique features and concerns stimulated us to write this review article on the small-molecule-based optical detection of PA. This article describes the hydrogen bonding triggered optical detection of PA chronologically and categorically, with a particular focus on the development of small-molecule-based fluorophores reported over the last two decades. Special attention is conferred on how the single driver, hydrogen bonding, can bring about distinct and dissimilar phenomenal changes (such as aggregation, chelation, charge transfer, electron transfer, proton transfer, energy transfer, excimer formation, etc.) on the variation of the signaling and/or the binding unit of the probe molecules upon interaction with PA to reach the single destiny of the optical detection of the explosive. Finally, conclusions are made on the key points and achievements of the optical detection of PA along with the existing potential challenges for young researchers who will develop innovations in this field. We believe that the article will be an important addition to the existing literature on PA sensing.

Disaggregation-induced resurgence of quenched emission of a self-assembled bis-indole system: photophysics, energetics, and dynamics.

Disaggregation-induced emission enhancement was studied using a self-aggregated bis-indole derivative, 3,3'-bisindolyl(phenyl)methane (BIPM), and ß-CD molecules were employed for the emission recovery. In our recent study, BIPM molecules were found to exhibit weak emission efficiency in pure water due to aggregation-caused quenching (ACQ) effects. In the present study, we employed a simple, effective, biologically benign, and sustainable strategy in an attempt to disaggregate the BIPM self-aggregates into monomers to restore their emission efficiency. The ß-CD molecules were found to be effective in disaggregating the BIPM associations through tugging the monomers from their self-associations and encapsulating them into supramolecular nanocavities. The changes in the photophysical, dynamical, and thermodynamic properties associated with the disaggregation of the probe assemblies were studied by employing steady-state and time-resolved spectroscopy, isothermal titration calorimetry, and transmission electron microscopy with support from computational studies. The detailed photophysical and thermodynamic investigations on the disaggregation of the BIPM self-associations might provide significant insights towards its suitability for diverse biological and pharmaceutical applications.

Prokaryotic ncRNAs: Master regulators of gene expression.

ncRNA plays a very pivotal role in various biological activities ranging from gene regulation to controlling important developmental networks. It is imperative to note that this small molecule is not only present in all three domains of cellular life, but is an important modulator of gene regulation too in all these domains. In this review, we discussed various aspects of ncRNA biology, especially their role in bacteria. The last two decades of scientific research have proved that this molecule plays an important role in the modulation of various regulatory pathways in bacteria including the adaptive immune system and gene regulation. It is also very surprising to note that this small molecule is also employed in various processes related to the pathogenicity of virulent microorganisms.

Genome structure and genetic diversity in the Ebola virus.

Ebola is a deadly pathogen responsible for Ebola virus disease, first came to prominence in the year 1976. This rapidly evolving virus imposed a serious threat to the human population in the last few decades and also continues to be a probable threat to our race. A better understanding of the virus in terms of its genomic structure is very much needed to develop an effective antiviral therapy against this deadly pathogen. Complete knowledge of its genomic structure and variations will help us and the entire scientific community to design effective therapy in terms of either vaccine development or the development of proper antiviral medicine.

SARS-CoV-2 and other human coronaviruses: Mapping of protease recognition sites, antigenic variation of spike protein and their grouping through molecular phylogenetics.

In recent years, a total of seven human pathogenic coronaviruses (HCoVs) strains were identified, i.e., SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Here, we performed an analysis of the protease recognition sites and antigenic variation of the S-protein of these HCoVs. We showed tissue-specific expression pattern, functions, and a number of recognition sites of proteases in S-proteins from seven strains of HCoVs. In the case of SARS-CoV-2, we found two new protease recognition sites, each of calpain-2, pepsin-A, and caspase-8, and one new protease recognition site each of caspase-6, caspase-3, and furin. Our antigenic mapping study of the S-protein of these HCoVs showed that the SARS-CoV-2 virus strain has the most potent antigenic epitopes (highest antigenicity score with maximum numbers of epitope regions). Additionally, the other six strains of HCoVs show common antigenic epitopes (both B-cell and T-cell), with low antigenicity scores compared to SARS-CoV-2. We suggest that the molecular evolution of structural proteins of human CoV can be classified, such as (i) HCoV-NL63 and HCoV-229E, (ii) SARS-CoV-2, and SARS-CoV and (iii) HCoV-OC43 and HCoV-HKU1. In conclusion, we can presume that our study might help to prepare the interventions for the possible HCoVs outbreaks in the future.

Repurposing Drugs, Ongoing Vaccine, and New Therapeutic Development Initiatives Against COVID-19.

As the COVID-19 is still growing throughout the globe, a thorough investigation into the specific immunopathology of SARS-CoV-2, its interaction with the host immune system and pathogen evasion mechanism may provide a clear picture of how the pathogen can breach the host immune defenses in elderly patients and patients with comorbid conditions. Such studies will also reveal the underlying mechanism of how children and young patients can withstand the disease better. The study of the immune defense mechanisms and the prolonged immune memory from patients population with convalescent plasma may help in designing a suitable vaccine candidate not only for the current outbreak but also for similar outbreaks in the future. The vital drug candidates, which are being tested as potential vaccines or therapeutics against COVID-19, include live attenuated vaccine, inactivated or killed vaccine, subunit vaccine, antibodies, interferon treatment, repurposing existing drugs, and nucleic acid-based vaccines. Several organizations around the world have fast-tracked the development of a COVID-19 vaccine, and some drugs already went to phase III of clinical trials. Hence, here, we have tried to take a quick glimpse of the development stages of vaccines or therapeutic approaches to treat this deadly disease.

In silico identification and characterization of sensory motifs in the transcriptional regulators of the ArsR-SmtB family.

The ArsR-SmtB family of proteins displays the greatest diversity among the bacterial metal-binding transcriptional regulators with regard to the variety of metal ions that they can sense. In the presence of increased levels of toxic heavy metals, these proteins dissociate from their cognate DNA upon the direct binding of metal ions to the appropriate sites, designated motifs on the proteins, either at the interface of the dimers or at the intra-subunit locations. In addition to the metal-mediated regulation, some proteins were also found to control transcription via redox reactions. In the present work, we have identified several new sequence motifs and expanded the knowledge base of metal binding sites in the ArsR-SmtB family of transcriptional repressors, and characterized them in terms of the ligands to the metal, distribution among different phyla of bacteria and archaea, amino acid propensities, protein length distributions and evolutionary interrelationships. We built structural models of the motifs to show the importance of specific residues in an individual motif. The wide abundance of these motifs in sequences of bacteria and archaea indicates the importance of these regulators in combating metal-toxicity within and outside of the hosts. We also show that by using residue composition, one can distinguish the ArsR-SmtB proteins from other metalloregulatory families. In addition, we show the importance of horizontal gene transfer in microorganisms, residing in similar habitats, on the evolution of the structural motifs in the family. Knowledge of the diverse metalloregulatory systems in microorganisms could enable us to manipulate specific genes that may result in a toxic metal-free environment.

Metal homeostasis in bacteria: the role of ArsR-SmtB family of transcriptional repressors in combating varying metal concentrations in the environment.

Bacterial infections cause severe medical problems worldwide, resulting in considerable death and loss of capital. With the ever-increasing rise of antibiotic-resistant bacteria and the lack of development of new antibiotics, research on metal-based antimicrobial therapy has now gained pace. Metal ions are essential for survival, but can be highly toxic to organisms if their concentrations are not strictly controlled. Through evolution, bacteria have acquired complex metal-management systems that allow them to acquire metals that they need for survival in different challenging environments while evading metal toxicity. Metalloproteins that controls these elaborate systems in the cell, and linked to key virulence factors, are promising targets for the anti-bacterial drug development. Among several metal-sensory transcriptional regulators, the ArsR-SmtB family displays greatest diversity with several distinct metal-binding and nonmetal-binding motifs that have been characterized. These prokaryotic metolloregulatory transcriptional repressors represses the expression of operons linked to stress-inducing concentrations of metal ions by directly binding to the regulatory regions of DNA, while derepression results from direct binding of metal ions by these homodimeric proteins. Many bacteria, e.g., Mycobacterium tuberculosis, Bacillus anthracis, etc., have evolved to acquire multiple metal-sensory motifs which clearly demonstrate the importance of regulating concentrations of multiple metal ions. Here, we discussed the mechanisms of how ArsR-SmtB family regulates the intracellular bioavailability of metal ions both inside and outside of the host. Knowledge of the metal-challenges faced by bacterial pathogens and their survival strategies will enable us to develop the next generation drugs.

Study on minerals status of dairy cows and their supplementation through area specific mineral mixture in the state of Jharkhand.

BACKGROUND: Deficiency of macro and micro-minerals in the ration of dairy cows adversely affects growth, milk production and reproduction efficiency. It is essential to examine mineral concentrations in feeds offered to dairy cows in practical farms. METHODS: Two villages from each taluka were selected at random for taking representative samples of feeds, forages and hair. Within the village, help was sought from village milk producers and district animal husbandry officer for identification of 4 to 5 farmers and collection of representative samples. All the samples were processed and analyzed for chemical composition as well as major macro and micro-minerals, using Inductively Coupled Plasma-Optical Emission Spectrometer. RESULTS: Ca content in wheat straw (0.29%), crushed maize (0.02%) and wheat bran (0.12%) was found to be below the critical level (0.30%). The P content in concentrate ingredients was high (0.26-0.96%), but low in dry roughages (0.06-0.12%). Cereal straws (0.14%) and grains (0.12%) were deficient in Mg. Feeds and forages were found to be adequate in K (1.50%). Cereals straws were found to be deficient in S (0.11%). Greens were good source of Cu (12.02 ppm). Wheat straw was found to be low in Zn (18 ppm), but high in Mn (225 ppm) and Fe (509 ppm). Local grasses and azolla green were found to be rich source of Co (>1.00 ppm). Se (0.63 ppm) was present in appreciable quantities in most of the feedstuffs. CONCLUSIONS: From the present study, it was apparent that the feeds and forages available in the state of Jharkhand may not meet the requirements for Ca, P, Mg, Cu, Zn and Co in order to sustain a milk production of ~10 kg/day. Therefore, it is necessary to supplement these deficient minerals through area specific mineral mixture in the ration of dairy cows for improving productivity and reproduction efficiency.

Comparative efficacy of an organic Acid blend and bacitracin methylene disalicylate as growth promoters in broiler chickens: effects on performance, gut histology, and small intestinal milieu.

This study evaluated the efficacy of organic acids as a growth promoter for broiler chickens relative to antibiotic growth promoters (AGPs). Broiler chickens were supplemented with graded doses of an organic acid blend (OAB, 1 g and 2 g/kg diet) and bacitracin methylene disalicylate (BMD, 0.5 g and 1 g/kg diet) for 35 days. Supplementation of OAB improved (P < .001) feed conversion ratio (FCR) and increased protein accretion (P < .001). Dietary acidification caused pH of the gizzard to decline linearly (P < .01) with the dose of supplemental OAB. In the lower intestine, pH remained unaffected by dietary treatments. Unlike BMD, supplemental OAB selectively promoted growth of lactobacilli in the small intestine. Moreover, compared to BMD, OAB tended to maintain the villi in the small intestine at a greater height. Although benefits of exceeding the dose of supplemental organic acids more than 1 g/kg diet are not always conspicuous, based on the live weight and feed conversion data, supplementation of 2 g organic acid per kg diet may be recommended for total replacement of AGPs in broiler diet.

Performance traits and metabolic responses in goats (Capra hircus) supplemented with inorganic trivalent chromium.

The effects of supplemental chromium (Cr) as chromic chloride hexahydrate in incremental dose levels (0, 0.5, 1.0, and 1.5 mg/day for 240 days) on metabolism of nutrients and trace elements were determined in dwarf Bengal goats (Capra hircus, castrated males, average age 3 months, n = 24, initial mean body weight 6.4 +/- 0.22 kg). Live weight increased linearly (p < 0.05) with the level of supplemental Cr. Organic matter and crude protein digestibility, intake of total digestible nutrients, and retention of N (g/g N intake) increased (p < 0.05) in a dose-dependent linear manner. Serum cholesterol and tryacylglycerol concentrations changed inversely with the dose of supplemental Cr (p < 0.01). Supplemental Cr positively influenced retention of copper and iron (p < 0.05) causing linear increase (p < 0.01) in their serum concentrations. It was concluded that Cr supplementation may improve utilization of nutrients including the trace elements and may also elicit a hypolidemic effect in goats. However, further study with regards to optimization of dose is warranted.