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I'timād-ud-Daulah (Mîrzâ Gıyâsüddîn Muhammed Tahrânî) is not from Iran, contrary to what is believed, but one of the Turks emigrated from Iran to India. The Tomb of I'timād-ud-Daulah is located in the center of the city of Agra in the state of Uttar Pradesh in India, in the north of the Agra Fort and in the east of the Yamuna River. In the inscriptions on the building, there are the dates of h. 1037 (g. 1627/28) and h. 1039 (g. 1629/30) and the signature of Abd al Nabi alQurashi, the calligrapher. Although there is not an inscription, endowment or official document about the founder, it is accepted that it was built by Nur Jahan, one of the important woman founders of the period, for her father Mîrzâ Gıyâsüddîn Muhammed Tahrânî and her mother Asmat Begum. The basis of this is the fact that the tombs she built for her husband Jahangir Shah and herself in Lahore are quite similar to I'timād-ud-Daulah in terms of architectural and decorative characteristics. The tomb has an important place in the 17th century Turkish-Islamic architecture. It stands out in many ways among other tombs built during the Mughal period in India. It also serves as an example for the pure tombs or complex structures that include tombs that were built in the later period. The tomb is a pioneer in design in terms of architectural decorations of the Taj Mahal. However, although it is the source of inspiration for Taj Mahal’s designs, it is not as well-known as Taj Mahal. In addition to the fact that the building was the pioneer of many novelties among Turkish-Islamic buildings located in India that had not been seen before, it adhered to the Mughal tomb architecture tradition with its plan schema. Through this study, the location, history, founder and architectural and decorative characteristics of the tomb of I'timād-ud-Daulah have been examined, and it has been aimed at contributing the further studies on Mughal period architecture in India and introducing the building, which has not been emphasized so far, to the world of science. [ABSTRACT FROM AUTHOR]

Enzymes may hydrolyse cellulose to produce glucose, which is then utilized to make ethanol, organic acids and other compounds. Cellulases are a class of hydrolytic enzymes that can break down cellulose, the most prevalent organic polymer, into smaller sugar molecules like glucose subunits. Due to its exorbitant price and low specific activity, cellulase accounts for only 50% of the total cost of hydrolysis. This enzyme is employed in a variety of industries, including the food, beverage, textile, laundry, paper and pulp sectors. As a result, extensive research has been done to find new microorganisms that produce cellulose enzymes more effectively and with higher specific activity. The evaluation of cellulase producing fungi isolated from various soil samples obtained at chosen sites in the Agra district was the main goal of this study. Using carboxymethylcellulose (CMC) agar medium, a total of 18 fungi were isolated in the form of pure colonies and tested for cellulose degrading abilities based on the presence of clear zones. Seven of the 18 fungal strains that were isolated were found to have cellulolytic activity. Endoglucanase "CMCase" (carboxymethyl cellulase) measured the cellulase activity. After quantitative assay it was found that isolated fungi SF3 had highest cellulase activity. [ABSTRACT FROM AUTHOR]

Historians have often highlighted the centrality of bazaars and the streets in urban public life in India as a space for politics and mobilisation. Historically, these bazaars and streets have been the domain of men, while spaces created by dominant urban planning logics like sequestered parks and enclosed marketplaces are marked by exclusion across various axes. Where do women then find opportunities for leisure, solidarity, chance encounter, or discursive politics? The paper explores this question through a case study of a low-income riverside settlement in Agra using ethnographic field work conducted in 2019. This included observations, interviews, and group discussions with residents, community leaders, and police officials, and a systematic review of local and national news reports. The paper finds that for women, public spaces like riverbanks, streets, and large parks are characterised by a 'mahaul' (translated here as affective environment) that is risky and 'kharab' (immoral or corrupt) due to their sticky affective association with harassment, transgression, romance, and the risk of elopements. Instead, women find opportunities for leisure and sociality by coming together on cots in shared courtyards or rooftops within their neighbourhood – these form their 'enclosed outside' where they find opportunities for sociality, leisure (which exists simultaneously with work), and discussion. By centring women's experiences, vocabularies, and everyday relationship with public spaces, and underscoring the register of 'affect' in these experiences, this paper makes an important contribution to the growing literature on gendering right to the city and the feminist argument for women's right to leisure spaces. The paper also centres the importance of local built elements like shared courtyards within a neighbourhood especially for women, with implications for urban planning and design. [ABSTRACT FROM AUTHOR]

Foundations are one of the oldest organizational forms globally; their number and resources, as well as their socio-political and economic importance, have steadily continued to grow. Yet, foundations' attributes, activities, and actual achievements remain underexplored and poorly understood. This is particularly noticeable in the context of global policy and transnational administration, an area where foundations tend to be subliminal players, acting as a widely unrecognized socio-political undercurrent. Addressing the resulting need for better and alternative conceptualizations of foundations, our paper uses French pragmatic sociology of critique (FPSC), a non-structuralist, post-Bourdesian, approach to sociology, to theorize philanthropic foundations within the policy agora. Through FPSC, we present foundations as a composite setup of activity, where critically reflexive actors bring normative ideologies and knowledge to policy, providing a new avenue for how scholarship can interpret and critique foundations and their influence. [ABSTRACT FROM AUTHOR]

ABSTRACT Staphylococcus aureus produces various hemolysins regulated by the Agr-QS system, except β-hemolysin encoded by the gene hlb. A classical laboratory S. aureus strain RN4220 displays only the β-hemolysin phenotype. It was suspected that the 8A mutation at the end of its agrA gene delayed the expressions of hla and RNAIII, then failed to express α- and δ-hemolysins. However, hla gene expression was detected at the later culture time without α-hemolysin phenotype, the reason for such a phenotype has not been clearly understood. We created hlb knockout and complementary mutants via homologous recombination in RN4220 and NRS049, two strains that normally produce β-hemolysin and carry agrA mutation. We found interestingly that the presence or absence of α-hemolysin phenotype in such strains depended on the expression of β-hemolysin instead of agrA mutations, which only inhibited δ-hemolysin expression. The hemolysis phenotype was verified by the Christie-Atkinson-Munch-Peterson (CAMP) test. Quantitative reverse transcription PCR was carried out to evaluate the relative gene expressions of hlb, hla, and RNAIII. The construction of mutants did not affect the agrA mutation status. We demonstrate that the absence of α-hemolysin in S. aureus RN4220 and NRS049 strains is attributed to their production of β-hemolysin instead of agrA mutation. Our findings broaden the understanding of the molecular mechanisms that control hemolysin expression in S. aureus that is crucial for the development of new therapeutic strategies to combat S. aureus infections.IMPORTANCEα-Hemolysin is a critical virulence factor in Staphylococcus aureus and its expression is largely controlled by the Agr-QS system. Nonetheless, the hemolysis phenotype and the regulation of the Agr-QS system in S. aureus still hold many mysteries. Our study finds that it is the expression of β- hemolysin rather than the agrA mutation that inhibits the function of the α-hemolysin in an important S. aureus strain RN4220 and a clinical strain presents a similar phenotype, which clarifies the misunderstood hemolytic phenotype and mechanism of S. aureus. Our findings highlight the interactions among different toxins and their biological roles, combined with QS system regulation, which is ultimately the true underlying cause of its virulence. This emphasizes the importance of considering the collaborative action of various factors in the infection process caused by this significant human pathogen.

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Background: Membrane vesicles (MVs) are nanoscale vesicular structures produced by bacteria during their growth in vitro and in vivo. Some bacterial components can be loaded in bacterial MVs, but the roles of the loaded MV molecules are unclear. Methods: MVs of Staphylococcus aureus RN4220 and its derivatives were prepared. Dynamic light scattering analysis was used to evaluate the size distribution, and 4D-label-free liquid chromatography-tandem mass spectrometry analysis was performed to detect protein composition in the MVs. The site-mutation S. aureus RN4220-1hld and agrA deletion mutant RN4220-1agrA were generated via allelic replacement strategies. A hemolysis assay was performed with rabbit red blood cells. CCK-8 and lactate dehydrogenase release assays were used to determine the cytotoxicity of S. aureus MVs against RAW264.7 macrophages. The serum levels of inflammatory factors such as IL-6, IL-1β, and TNFα in mice treated with S. aureus MVs were detected with an enzyme-linked immunosorbent assay kit. Results: Delta-hemolysin (Hld) was identified as a major loaded factor in S. aureus MVs. Further study showed that Hld could promote the production of staphylococcal MVs with smaller sizes. Loaded Hld affected the diversity of loaded proteins in MVs of S. aureus RN4220. Hld resulted in decreased protein diversity in MVs of S. aureus. Site-mutation (RN4220-1hld) and agrA deletion (RN4220-1agrA) mutants produced MVs (ΔhldMVs and ΔagrAMVs) with a greater number of bacterial proteins than those derived from wild-type RN4220 (wtMVs). Moreover, Hld contributed to the hemolytic activity of wtMVs. Hld-loaded wtMVs were cytotoxic tomacrophage RAW264.7 cells and could stimulate the production of inflammatory factor IL-6 in vivo. Conclusion: This study presented that Hld was a major loaded factor in S. aureus MVs, and the loaded Hld played vital roles in the MV-property modification. [ABSTRACT FROM AUTHOR]

ABSTRACT The Agr quorum sensing (QS) system is known to contribute to biofilm formation in Listeria monocytogenes. Cinnamaldehyde, a natural food preservative, is considered an inhibitor of Agr-mediated QS in L. monocytogenes. However, the exact mechanism by which cinnamaldehyde acts on Agr remains unclear. In this study, we assessed the effects of cinnamaldehyde on the histidine kinase AgrC and the response regulator AgrA in the Agr system. AgrC kinase activity was not influenced by cinnamaldehyde, and binding between AgrC and cinnamaldehyde was not observed when microscale thermophoresis (MST) was performed, indicating that AgrC was not the target of cinnamaldehyde. AgrA is specifically bound to the agr promoter (P2) to activate the transcription of the Agr system. However, AgrA-P2 binding was prevented by cinnamaldehyde. The interaction between cinnamaldehyde and AgrA was further confirmed with MST. Two conserved amino acids, Asn-178 and Arg-179, located in the LytTR DNA-binding domain of AgrA, were identified as the key sites for cinnamaldehyde-AgrA binding by alanine mutagenesis and MST. Coincidentally, Asn-178 was also involved in the AgrA-P2 interaction. Taken together, these results suggest that cinnamaldehyde acts as a competitive inhibitor of AgrA in AgrA-P2 binding, which leads to suppressed transcription of the Agr system and reduced biofilm formation in L. monocytogenes. IMPORTANCE Listeria monocytogenes can form biofilms on various food contact surfaces, posing a serious threat to food safety. Biofilm formation of L. monocytogenes is positively regulated by the Agr quorum sensing system. Thus, an alternative strategy for controlling L. monocytogenes biofilms is interfering with the Agr system. Cinnamaldehyde is considered an inhibitor of the L. monocytogenes Agr system; however, its exact mechanism of action is still unclear. Here, we found that AgrA (response regulator), rather than AgrC (histidine kinase), was the target of cinnamaldehyde. The conserved Asn-178 in the LytTR DNA-binding domain of AgrA was involved in cinnamaldehyde-AgrA and AgrA-P2 binding. Therefore, the occupation of Asn-178 by cinnamaldehyde suppressed transcription of the Agr system and reduced biofilm formation in L. monocytogenes. Our findings could provide a better understanding of the mechanism by which cinnamaldehyde inhibits L. monocytogenes biofilm formation.

DNA barcoding is a rapid advance technique to identify species at the molecular level. Since the orderAraneae is the least known group among the Arthropods at the molecular level, the present study was undertaken to enrich the DNA barcode record on the most predominant spiders of semi-arid habitat of Agra region. The DNA barcoding of MtCOI gene distinctly confirmed with the available morphological keys of five spider species i.e. Menemerus bivittatus, Menemerus nigli, Plexippus paykulli, Thomisus pugilis, Cyrtophora citricola. Amplified PCR product of mtCOI gene was 658 base pair. The maximum homology mtCOI nucleotide sequence of spiders showed 100 percent similarity with Plexippus paykulli, Thomisus pugilis and Cyrtophora citriocola while other species i.e. Menemerus bivittatus, Menemerus nigli showed 99 percent similarity. The maximum numbers of samples were observed from Salticidae group, which is the most predominant spider family of India. [ABSTRACT FROM AUTHOR]

Copyright of Art-Sanat Journal / Art-Sanat is the property of Art-Sanat and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nicotinamide adenine dinucleotide phosphate (NADPH) is the primary electron donor for reductive reactions that are essential for the biosynthesis of major cell components in all organisms. Nicotinamide adenine dinucleotide kinase (NADK) is the only enzyme that catalyzes the synthesis of NADP(H) from NAD(H). While the enzymatic properties and physiological functions of NADK have been thoroughly studied, the role of NADK in bacterial pathogenesis remains unknown. Here, we used CRISPR interference to knock down NADK gene expression to address the role of this enzyme in Staphylococcus aureus pathogenic potential. We find that NADK inhibition drastically decreases mortality of zebrafish infected with S. aureus. Furthermore, we show that NADK promotes S. aureus survival in infected macrophages by protecting bacteria from antimicrobial defense mechanisms. Proteome-wide data analysis revealed that production of major virulence-associated factors is sustained by NADK. We demonstrate that NADK is required for expression of the quorum-sensing response regulator AgrA, which controls critical S. aureus virulence determinants. These findings support a key role for NADK in bacteria survival within innate immune cells and the host during infection.

ABSTRACT Staphylococcus lugdunensis is a coagulase-negative Staphylococcus that emerges as an important opportunistic pathogen. However, little is known about the regulation underlying the transition from commensal to virulent state. Based on knowledge of S. aureus virulence, we suspected that the agr quorum sensing system may be an important determinant for the pathogenicity of S. lugdunensis. We investigated the functions of the transcriptional regulator AgrA using the agrA deletion mutant. AgrA played a role in cell pigmentation: ΔargA mutant colonies were white while the parental strains were slightly yellow. Compared with the wild-type strain, the ΔargA mutant was affected in its ability to form biofilm and was less able to survive in mice macrophages. Moreover, the growth of ΔagrA was significantly reduced by the addition of 10% NaCl or 0.4 mM H2O2 and its survival after 2 h in the presence of 1 mM H2O2 was more than 10-fold reduced. To explore the mechanisms involved beyond these phenotypes, the ΔagrA proteome and transcriptome were characterized by mass spectrometry and RNA-Seq. We found that AgrA controlled several virulence factors as well as stress-response factors, which are well correlated with the reduced resistance of the ΔagrA mutant to osmotic and oxidative stresses. These results were not the consequence of the deregulation of RNAIII of the agr system, since no phenotype or alteration of the proteomic profile has been observed for the ΔRNAIII mutant. Altogether, our results highlighted that the AgrA regulator of S. lugdunensis played a key role in its ability to become pathogenic. IMPORTANCE Although belonging to the natural human skin flora, Staphylococcus lugdunensis is recognized as a particularly aggressive and destructive pathogen. This study aimed to characterize the role of the response regulator AgrA, which is a component of the quorum-sensing agr system and known to be a major element in the regulation of pathogenicity and biofilm formation in Staphylococcus aureus. In the present study, we showed that, contrary to S. aureus, the agrA deletion mutant produced less biofilm. Inactivation of agrA conferred a white colony phenotype and impacted S. lugdunensis in its ability to survive in mice macrophages and to cope with osmotic and oxidative stresses. By global proteomic and transcriptomic approaches, we identified the AgrA regulon, bringing molecular bases underlying the observed phenotypes. Together, our data showed the importance of AgrA in the opportunistic pathogenic behavior of S. lugdunensis allowing it to be considered as an interesting therapeutic target.

In the Baburid State, which was established in 1526 in India, the capital city was changed from time to time due to political, economic and social reasons. In this context, the cities of Agra, Delhi, Fatehpur Sikri and Lahore have assumed capital positions at different times. However, in the event of a change or relocation of the capital, the star of the city, which was previously the capital, never faded and its vitality continued since Agra and Delhi, as well as being commercial attractions, were built on ancient history. Fetihpur Sikri hosted religious and spiritual personalities. Lahore, on the other hand, had the task of being an important intersection connecting land trade with other regions of India, as well as being of military importance with its geostrategic location. The time limitation of this study, which deals with the capital cities in Baburid State, is the cross-section between 1526 and 1707. The sources used in the study are the sources written by the Baburid rulers or their relatives such as Vekayi (Baburnama), Akbarnama and Tuzuk i Jahangiri (Jahangirnama), and the memoirs and reports containing the impressions of travelers and merchants such as Bernier and Tavernier who went to India. In addition, the current literature on Indian and Baburid city history studies was also benefited. [ABSTRACT FROM AUTHOR]

The study aims to define the problems facing rice farmers in Aqra, as well as to identify the relationship between the problems and each of the independent variables (age, educational level, cultivated area, number of working years). The final research sample reached (100) respondents excluding the sample of pre-test of (20) respondents, data were collected by means of the questionnaire form which consisted of two parts, the first of which, the independent variables studied, and included the second part, the dependent variable and included (30) problems, and the validity of the form was confirmed by presenting it to specialists in agricultural extension and was distributed to a sample A preliminary (pre-test) to ensure its reliability. The results of the study showed that the highest problem take the first rank was (the lack of support and interest of the state in the crop and rice growers) and the least problem was (the lack of modern techniques used to harvest the rice crop), and the study showed a significant correlation between the problems and each of the following variables, age ,The educational level, the cultivated area, the number of working years, and the researchers recommended the need to address the problems facing the farmers through appropriate treatments for each problem as well as the state's interest in farmers by providing their requirements and needs And support them financially and morally.

Analysing old maps and correlating patterns with remote sensing (RS) images have been a useful technique for identifying features of cultural heritage. The present work has conducted a geospatial analysis of Mughal Agra by comparing historical maps and satellite imagery. This paper make two distinct contributions: (1) it expands existing findings on the riverfront Mughal city by identifying the position and footprint of all the riverfront complexes (by complex we mean property that have or had Mughal mansions, gardens or tombs) marked in a Mughal map of 1720, and (2) it makes original contribution by delineating the two-tiers of city walls and further attempts to comprehend the spatial transformations of the city since the Mughal period. This exploration resulted in recognizing traces of many lost historical built forms like city walls, gateways and riverfront complexes those of which have transformed, integrated, camouflaged or sometimes lost within the urban fabric of the present city of Agra. [ABSTRACT FROM AUTHOR]

The inevitable occurrence of diseases caused by bacterial pathogens is one of the main constraints in tilapia industry that has resulted in major economic losses. The study reveals the advantages of quorum sensing inhibition through nanotechnology in developing antivirulence drugs to control aquaculture pathogens using scientifically untapped medicinal plants, the ethnobotanicals. The ethnobotanical crude extracts (CEs) and biologically synthesized gold nanoparticles (CEs + AuNPs) of the Ilongot-Eǵongot community exhibit quorum sensing inhibition (QSI) activity through inhibition of the biofilm formation against gram-positive Streptococcus agalactiae. Furthermore, ethnobotanical CEs + AuNPs show much greater activity than its counterpart CEs in antibacterial and biofilm formation assay in S. agalactiae which is molecularly confirmed by gene expression analysis. The results indicate the potential of these ethnobotanicals for therapeutic approach in which it showed minimal expression of agrA gene linked in biofilm formation and connotes maximal inhibition of QS in S. agalactiae thereby can possibly inhibit bacterial resistance and virulence. [ABSTRACT FROM AUTHOR]

Antimicrobial drug discovery against drug-resistant bacteria is an urgent need. Beyond agents with direct antibacterial activity, anti-virulent molecules may also be viable compounds to defend against bacterial pathogenesis. Using a high throughput screen (HTS) that utilized Caenorhabditis elegans infected with methicillin-resistant Staphylococcus aureus (MRSA) strain of MW2, we identified 4-(1,3-dimethyl-2,3-dihydro-1H-benzimidazol-2-yl)phenol (BIP). Interestingly, BIP had no in vitro inhibition activity against MW2, at least up to 64 μg/ml. The lack of direct antimicrobial activity suggests that BIP could inhibit bacterial virulence factors. To explore the possible anti-virulence effect of the identified molecule, we first performed real-time PCR to examine changes in virulence expression. BIP was highly active against MRSA virulence factors at sub-lethal concentrations and down-regulated virulence regulator genes, such as agrA and codY. However, the benzimidazole derivatives omeprazole and pantoprazole did not down-regulate virulence genes significantly, compared to BIP. Moreover, the BIP-pretreated MW2 cells were more vulnerable to macrophage-mediated killing, as confirmed by intracellular killing and live/dead staining assays, and less efficient in establishing a lethal infection in the invertebrate host Galleria mellonella (p = 0.0131). We tested the cytotoxicity of BIP against human red blood cells (RBCs), and it did not cause hemolysis at the highest concentration tested (64 μg/ml). Taken together, our findings outline the potential anti-virulence activity of BIP that was identified through a C. elegans-based, whole animal based, screen.

Staphylococcus aureus produces various hemolysins regulated by the Agr-QS system, except β-hemolysin encoded by the gene hlb . A classical laboratory S. aureus strain RN4220 displays only the β-hemolysin phenotype. It was suspected that the 8A mutation at the end of its agrA gene delayed the expressions of hla and RNAIII , then failed to express α- and δ-hemolysins. However, hla gene expression was detected at the later culture time without α-hemolysin phenotype, the reason for such a phenotype has not been clearly understood. We created hlb knockout and complementary mutants via homologous recombination in RN4220 and NRS049, two strains that normally produce β-hemolysin and carry agrA mutation. We found interestingly that the presence or absence of α-hemolysin phenotype in such strains depended on the expression of β-hemolysin instead of agrA mutations, which only inhibited δ-hemolysin expression. The hemolysis phenotype was verified by the Christie-Atkinson-Munch-Peterson (CAMP) test. Quantitative reverse transcription PCR was carried out to evaluate the relative gene expressions of hlb , hla , and RNAIII . The construction of mutants did not affect the agrA mutation status. We demonstrate that the absence of α-hemolysin in S. aureus RN4220 and NRS049 strains is attributed to their production of β-hemolysin instead of agrA mutation. Our findings broaden the understanding of the molecular mechanisms that control hemolysin expression in S. aureus that is crucial for the development of new therapeutic strategies to combat S. aureus infections., Importance: α-Hemolysin is a critical virulence factor in Staphylococcus aureus and its expression is largely controlled by the Agr-QS system. Nonetheless, the hemolysis phenotype and the regulation of the Agr-QS system in S. aureus still hold many mysteries. Our study finds that it is the expression of β- hemolysin rather than the agrA mutation that inhibits the function of the α-hemolysin in an important S. aureus strain RN4220 and a clinical strain presents a similar phenotype, which clarifies the misunderstood hemolytic phenotype and mechanism of S. aureus . Our findings highlight the interactions among different toxins and their biological roles, combined with QS system regulation, which is ultimately the true underlying cause of its virulence. This emphasizes the importance of considering the collaborative action of various factors in the infection process caused by this significant human pathogen., Competing Interests: The authors declare no conflict of interest.

Staphylococcus aureus (S. aureus) is an aggressive opportunistic pathogen of prominent virulence and antibiotic resistance. These characteristics are due in part to the accessory gene regulator (agr) quorum-sensing system, which allows for the rapid adaptation of S. aureus to environmental changes and thus promotes virulence and the development of pathogenesis. AgrA is the agr system response regulator that binds to the P2 and P3 promoters and upregulates agr expression. In this study, we reveal that S. aureus AgrA is modified by covalent binding of CoA (CoAlation) in response to oxidative or metabolic stress. The sites of CoAlation were mapped by liquid chromatography tandem mass spectrometry (LC–MS/MS) and revealed that oxidation-sensing Cys199 is modified by CoA. Surface plasmon resonance (SPR) analysis showed an inhibitory effect of CoAlation on the DNA-binding activity, as CoAlated AgrA had significantly lower affinity towards the P2 and P3 promoters than non-CoAlated AgrA. Overall, this study provides novel insights into the mode of transcriptional regulation in S. aureus and further elucidates the link between the quorum-sensing and oxidation-sensing roles of the agr system.

Fluoride (F−), a harmful compound if present in high concentration, is typically found in groundwater. It is important to investigate the F− concentrations in groundwaters of areas where individuals use groundwater for drinking purposes. The objectives of this study were: (a) to estimate the F− exposure, and (b) to assess the non-carcinogenic risk through consumption of groundwater among urban population (different age groups) of Agra city. A total of 28 groundwater samples were collected from Agra city in May 2016, which comprised 22 samples from hand pump and 6 samples from tube wells from shallow aquifers at different sites. The F− concentrations varied from 0.90 to 4.12 mg/L with an average value of 1.88 mg/L. The results obtained reveal that about 64% of the samples exceeded the F− permissible limit of 1.5 mg/L. Nevertheless, 32% of the samples were well within the WHO drinking water guidelines and 3.5% of the samples from the groundwater were below the 1.0 mg/L threshold. The maximum estimated exposure doses were 0.69, 0.31 and 0.12 mg/kg/day for infants, children and adults, respectively. A dental fluorosis becomes evident when the results obtained are compared with an oral reference dose of 0.06 mg/kg/day. The hazard quotient (HQ) was found to be more than 1 for infants and children in all the studied areas which indicates that young consumers are more vulnerable to non-carcinogenic risk due to exposure of F−. On the other hand, the adults at about 71% of the sampled sites may be victims of non-carcinogenic risk. From the results obtained in this study, it is recommended that there be implementation of the appropriate remediation for defluoridation of water to circumvent the population from the probable health risks of F−. Image 1 • A total of 64% samples exceeded the standard limit of fluoride set by World Health Organization/Bureau of Indian Standards. • The estimated exposure doses (EDs) were 0.69, 0.31 and 0.12 mg/kg/day for infants, children, and adults, respectively. • The HQ was more than 1 for infants and children at all sites while it was greater than 1in 71% of adults. • There were potential non-carcinogenic effects on infants and children highly exposed to fluoride in the study area. [ABSTRACT FROM AUTHOR]

Antimicrobial drug discovery against drug-resistant bacteria is an urgent need. Beyond agents with direct antibacterial activity, anti-virulent molecules may also be viable compounds to defend against bacterial pathogenesis. Using a high throughput screen (HTS) that utilized Caenorhabditis elegans infected with methicillin-resistant Staphylococcus aureus (MRSA) strain of MW2, we identified 4-(1,3-dimethyl-2,3-dihydro-1H-benzimidazol-2-yl)phenol (BIP). Interestingly, BIP had no in vitro inhibition activity against MW2, at least up to 64 μg/ml. The lack of direct antimicrobial activity suggests that BIP could inhibit bacterial virulence factors. To explore the possible anti-virulence effect of the identified molecule, we first performed real-time PCR to examine changes in virulence expression. BIP was highly active against MRSA virulence factors at sub-lethal concentrations and down-regulated virulence regulator genes, such as agrA and codY. However, the benzimidazole derivatives omeprazole and pantoprazole did not down-regulate virulence genes significantly, compared to BIP. Moreover, the BIP-pretreated MW2 cells were more vulnerable to macrophage-mediated killing, as confirmed by intracellular killing and live/dead staining assays, and less efficient in establishing a lethal infection in the invertebrate host Galleria mellonella (p = 0.0131). We tested the cytotoxicity of BIP against human red blood cells (RBCs), and it did not cause hemolysis at the highest concentration tested (64 μg/ml). Taken together, our findings outline the potential anti-virulence activity of BIP that was identified through a C. elegans -based, whole animal based, screen. [ABSTRACT FROM AUTHOR]

The Jatavs of western UP during the 1930s fought a long campaign to be recognised as a separate caste. In this article, the progress and eventual success of that campaign are documented and described in detail for the first time. In addition, it is suggested that the Jatav efforts to establish a separate official identity cannot be fully understood within the framework provided by the notion of Sanskritisation. It is argued here that the Jatav endeavours need to be analysed as an expression of a purposeful Dalit engagement with the emerging political framework of the period. In particular, the negotiations about constitutional reform opened up the possibility of challenging the ways in which the colonial regime had previously used the names and numbers of castes as part of its techniques of governance. Dalit groups, often in association with Dr Ambedkar, intervened in the formal investigations conducted in relation to the reforms to expose the frailty and fiction of many of the assumptions of the colonial authorities. [ABSTRACT FROM AUTHOR]

Shit(ting) as a problem is not an a priori position. It is made a problem through socially mediated discursive and non‐discursive practices. Problematizations of human waste promoted by formal governance institutions have dominated the conversation, while the ways in which slum residents experience shit(ting) as a problem receive considerably less attention. This article examines how human waste and its attendant practices are represented as a problem in Agra, India. Using Foucauldian‐based analysis, this research makes visible problematizations of urban shit(ting) and exposes the divergent logics employed by urban actors. Ethnographic interviews and document analysis reveal six ways in which various actors experience shit(ting) as a problem—as: (1) inconvenient; (2) dangerous; (3) contagion; (4) undignified; (5) polluting; (6) primitive. Inconvenience was the problematization invoked most frequently by slum residents, but never by governance groups, meaning that issues of inconvenience were absent from formal planning processes. This absence can, in part, be attributed to the toilet's ability to address multiple problems simultaneously. Findings from this research support the call to acknowledge the situatedness of urban inquiry through analysis of problematizations. In doing so, scholars and practitioners gain access to a more complete toolkit for developing and evaluating urban sewage initiatives. [ABSTRACT FROM AUTHOR]

Background: Membrane vesicles (MVs) are nanoscale vesicular structures produced by bacteria during their growth in vitro and in vivo . Some bacterial components can be loaded in bacterial MVs, but the roles of the loaded MV molecules are unclear., Methods: MVs of Staphylococcus aureus RN4220 and its derivatives were prepared. Dynamic light scattering analysis was used to evaluate the size distribution, and 4D-label-free liquid chromatography-tandem mass spectrometry analysis was performed to detect protein composition in the MVs. The site-mutation S. aureus RN4220-Δhld and agrA deletion mutant RN4220-ΔagrA were generated via allelic replacement strategies. A hemolysis assay was performed with rabbit red blood cells. CCK-8 and lactate dehydrogenase release assays were used to determine the cytotoxicity of S. aureus MVs against RAW264.7 macrophages. The serum levels of inflammatory factors such as IL-6, IL-1β, and TNFα in mice treated with S. aureus MVs were detected with an enzyme-linked immunosorbent assay kit., Results: Delta-hemolysin (Hld) was identified as a major loaded factor in S. aureus MVs. Further study showed that Hld could promote the production of staphylococcal MVs with smaller sizes. Loaded Hld affected the diversity of loaded proteins in MVs of S. aureus RN4220. Hld resulted in decreased protein diversity in MVs of S. aureus . Site-mutation (RN4220-Δhld) and agrA deletion (RN4220-ΔagrA) mutants produced MVs ( Δ hld MVs and Δ agrA MVs) with a greater number of bacterial proteins than those derived from wild-type RN4220 ( wt MVs). Moreover, Hld contributed to the hemolytic activity of wt MVs. Hld-loaded wt MVs were cytotoxic to macrophage RAW264.7 cells and could stimulate the production of inflammatory factor IL-6 in vivo ., Conclusion: This study presented that Hld was a major loaded factor in S. aureus MVs, and the loaded Hld played vital roles in the MV-property modification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Lv, Shang, Yang, Wang, Hu, Huang, Zhang, Yuan, Huang and Rao.)

Men who have sex with men (MSMs) are a group of high-risk individuals in India, who have remained neglected for a long time. Stigma, discrimination and laws criminalizing sex between men undermine access to HIV/AIDS and other health care services. In this study, we determined the seroprevalence and risk factors for HIV and syphilis infections among a group of MSMs attending an Integrated Counseling & Testing Centre (ICTC) at Agra during 2009–11. The results have been compared with those in other regions of the country. There were 277 MSMs registered with a nongovernmental organization (NGO), Khushi, involved in a Targeted Intervention (TI) project, who were tested for HIV and venereal disease research laboratory (VDRL) infections. Sociodemographic profile, risk factors, sexual identity, general health care access, and previous HIV and/or sexually transmitted infection (STI) testing, etc., were documented. The prevalence of HIV and syphilis infections among the MSMs are 11.9% (33/277) and 11.1% (31/277), respectively. There were 74% of them in the age group of 15–35 years, illiterate, and having no specific job. Alcohol, drug abuse, and high-risk behavior were common as they preferred to be in groups. There were 70% of HIV-positive MSMs, and 87% of those having sexually transmitted diseases (STDs) were unmarried and had multiple partners. Some of the MSMs were married and in bisexual relationships, and they might serve as an important bridge population between men and women. High prevalence of HIV and STDs in this group emphasizes the need for public health interventions aimed at reduction of risky behavior, education and counseling to urge them to seek health care advice when needed. [ABSTRACT FROM AUTHOR]

Abstract: Rethinking the logic of institutional environments aiming to facilitate agroforestry smallholders in economic development, this article compares smallholder input supply systems for crop and tree seeds in sub‐Saharan Africa and reflects on two basic challenges: (1) how to develop a large number of relevant tree crops for different agroecologies, (2) how to reach smallholders in rural areas. Policy options for improving agroforestry input supply systems are discussed, whereby our article concludes with suggestions how sectoral approaches for crop seed systems can be modified to agroforestry seed‐seedling systems. Biophysical differences have practical implications for how the logic of the ‘African green revolution’ would be translated into a corresponding revolution for agroforestry. [ABSTRACT FROM AUTHOR]