The role of matrix metalloproteinases in leukocyte migration and collagen degradation in tuberculosis

Tuberculosis (TB) causes disease worldwide and multi-drug resistance is rising. Matrix metalloproteinases (MMPs) cause immunopathological lung matrix destruction, which results in transmission, morbidity and mortality. Collagen is the primary structural fibril of the lung and I primarily studied two collagenases: secreted MMP-8, and membrane bound MMP-14, and also the stromelysin MMP-10, which activates not only MMP-8 but another collagenase MMP-1. Human monocyte and macrophages were stimulated with Mtb H37Rv, BCG, ESAT-6 peptides or Conditioned Media from Mtb infected monocytes (CoMTb). MMP concentrations were measured by Luminex bead array and ELISA. Gene expression was quantified by RT-PCR. Immunohistochemistry was performed on biopsies. Flow cytometry quantified MMP-14 expression. Fluorescent microscopy detected MMP-14 and monocyte driven fluorescent collagen degradation. Monocyte migration was measured by the agarose spot assay. MMP-8 was increased in the plasma in TB compared to both respiratory symptomatics and controls (both p<0.001). MMP-10 was increased in the respiratory secretions of patients with TB compared to controls (p<0.05). Mtb drove up to a 31.5 fold increase in MMP-10 secretion from macrophages (both p<0.001). Mtb caused 3.5 fold more MMP-10 secretion from macrophages than BCG (p<0.001) and a specific peptide from ESAT-6 drove MMP-10 secretion from macrophages. In induced sputum, MMP-14 mRNA was increased 3.3-fold in TB compared to controls and positively correlated with infiltration on chest radiograph (both p<0.05). Macrophages of TB granulomas in biopsies stained strongly positive for MMP-14. Mtb increased monocyte MMP-14 surface expression 31.7-fold (p<0.05) and CoMTb 17.5-fold (p<0.01). Mtb infected monocytes degraded collagen, with co-localised MMP-14 surface expression. Monocytes migrated to the edge of CoMTb impregnated agarose drops, expressing MMP-14 on migration. Inhibition of MMP-14 activity with a neutralising antibody, decreased Mtb driven collagen degradation by 73% (p< 0.001) and CoMTb driven monocyte migration by 44% (p<0.001). These data shows that, MMP-1, -8, -10 and -14 cause immunopathology and regulate leukocyte migration in TB.Open Acces

Affective Activism and Digital Archiving: Relief Work and Migrant Workers during the Covid-19 Lockdown in India

This article traces what I term the affective activism of volunteers, civil society organiza- tions, and lorry drivers engaged in relief work to assist stranded migrant workers wanting to travel home during the first wave of the coronavirus pandemic and national lockdown in India. I define affective activism as an archival practice that is driven by relief figures’ af- fects of fear, anger, and aspirations—in this instance, toward their legal and administrative accountability to funders. Drawing on my ethnographic work in a relief network and using independent interviews I conducted, this article critically compares two modalities of dig- ital archiving conducted by relief figures: collecting migrant workers’ Aadhaar—unique biometric number identifiers issued to Indians—and digitally archiving their relief efforts through videos, voice-notes, and WhatsApp Messenger screenshots. I argue that relief fig- ures expressed their anxieties in the form of talismanic beliefs that records of Aadhaar and their material infrastructure would keep safe the migrant workers they were trying to help. Alternately, and sometimes, concomitantly, they performatively deployed Whatsapp artifacts to support their accountability in the face of bureaucratic and political specters. Both forms highlight the desire of relief figures to exceed paper forms and state practices in their archival impulses

The power of the ‘universal’: caste and missionary medical discourses of alcoholism in the Telugu print sphere, 1900–1940

This article explores missionary medical discourses in three Telugu journals published in the early twentieth century, to analyse how caste pivoted denunciations of alcohol, especially toddy and arrack, in the Madras Presidency and the Hyderabad state. It argues that one women’s missionary journal, Vivekavathi, deployed medical knowledge to formulate subtle and occasionally explicit condemnations of toddy and arrack as unclean and unhealthy substances. The journal relied on universal medical and missionary, British and American knowledge frameworks to mark out Dalits and other marginalised castes as consumers of these local beverages. This stigma was conjured through medical narratives of marginalised castes as lacking in the knowledge of alcohol’s relation to digestion, toddy’s role in ruining maternal and child nutrition, the unhygienic environment of arrack shops and their propensity to ‘alcoholism’. However, this article also traces counter-caste voices who too invoked ‘the power of the universal’ to dispel caste stigma against marginalised castes. While both sets of voices deployed medical ‘enslavement’ to alcohol as an interpretive move, they differed in their social imperatives and political imaginaries, defined in caste terms. This article explores a third set of implications of the term ‘universal’ by analysing global medico-missionary narratives of alcohol in two other Telugu journals. On a methodological plane, this article also pushes for a hybrid reading of what counts for ‘scientific instruction’, where hymns, catechisms, parables and allegories are considered alongside conventional scientific experiments. In that sense, it upholds vernacular missionary publications as an invaluable resource for the social history of medicin

Biosorption of Heavy Metals using Individual and Mixed Cultures of Pseudomonas Aeruginosa and Bacillus Subtilis

Biosorption can be an effective technique for the treatment of heavy metal bearing waste water resulting from humuns and industrial activities. Several gram positive and gram negative bacteria have the ability to remove the heavy metals and there by making water contaminant free. It has been reported that attenuated bacterial biomass have greater biosorption capability than viable cells. In the present study, the biosorption of heavy metals using individual and mixed culture of attenuated bacteria (gram positive and gram negative) like Bacillus subtilis and Pseudomonas aeruginosa and parameters affecting the biosorption of heavy metals; such as time, pH, biomass concentration and initial metal concentration have been investigated. The batch experiments have been carried out using individual and mixed bacterial culture and the biosorption parameters were optimized using univariate procedures. The present study shows that 90.4% of biosorption of Mercury was observed for mixed cultures of Pseudomonas aeruginosa and Bacillus subtilis and 99.3% and 78.5% biosorption for individual cultures respectively. The time taken for maximum sorption of Mercury was 60, 40 and 40 minutes for mixed cultures of Pseudomonas aeruginosa and Bacillus subtilis. The optimum biomass concentration was found to be 2, 0.5 and 2.5 mg/ml for mixed cultures, Pseudomonas aeruginosa and Bacillus subtilis. pH 5 was found to be optimum for all the three biomass (two individual cultures; one mixed culture) for Mercury biosorption. Optimum temperature was $32\,^{\circ}C$ for all the three systems used in the present work. Adsorption isotherms of all the three metals with mixed cultures were best fitted with Langmuir and Freundlich isotherm models having highest value of regression coefficients with R2 0.99 which is close to one. Two kinetic models namely pseudo first order equation and pseudo second order equation were also tested for the biosorption processes. The biosorption of Chromium (VI) shows that 77.6% for mixed cultures, 60.5 and 81.3 for Pseudomonas aeruginosa and Bacillus subtilis respectively. The optimum biomass concentration was found to be 1.5, 1.5 and 2 for mixed cultures (Pseudomonas aeruginosa and Bacillus subtilis) at$32\,^{\circ}C$ and 3 pH. The equilibrium Arsenic biosorption were also conducted by using the same biomasses as mentioned above by achieving a sorption of 30%, 32% and 28% for mixed culture, Pseudomonas aeruginosa and Bacillus subtils)

Studies on Pigment Production by Microorganisms Using Raw Materials of Agro-industrial Origin

The recent awareness in human safety and environmental conservation has created fresh enthusiasm for natural sources of pigments. Compared to synthetic pigments, microbial pigments shows better biodegradability and higher compatibility with the environment, and have numerous applications from food to cosmetics. Identification of new microbial sources, utilization of low cost substrates and optimization of process parameters are the areas under focus towards economical pigment production. The present study aimed at screening and identification of microbial isolates from soil and water, which are having pigment producing ability. Efforts have been made to cultivate them on numerous cheaper and inexpensive substrates with no special conditions and supplements for effective pigment production. Furthermore, two carotenoid producing strains were also exploited on numerous inexpensive substrates at ambient conditions for pigment metabolites. While analyzing pigment metabolites in all cases, key parameters influencing pigment production by respective strains were optimized by utilizing statistical techniques like Taguchi method and response surface approaches wherever needed. The conditions for enhanced pigment production were established employing microbial isolates and purchase strains individually. The melanin producing Pseudomonas guinea, (bacterial strain) was isolated from marine water sample and was employed on vegetable waste for effective pigment production. Another strain of Bacillus safensis was isolated from garden soil and showed its ability to produce melanin on fruit waste extract (FWE). It is noteworthy that both melanins produced from marine and soil isolates showed antioxidant, photoprotective and metal ion chelation activities. Addressing garden soil, a new carotenoid producing bacterial strain Bacillus clausii was screened and cultivated on FWE for high yield pigment production. The pigment produced by this strain was observed to be a β-carotenoid type and its stability towards thermal treatment was also evaluated. Eying on the significance of carotenoids, microorganisms (Rhodotorula rubra, Xanthophyllomyces dendrorhous) in their developmental stage were purchased and studied for pigment production on various residues as sole substrates. The obtained yeasts showed improved carotenoids yield i.e. torularhodin and astaxanthin respectively on FWE. In a nut shell we could conclude that there is a huge scope for industrial scale production of Melanin and Carotinoid using easily available agro-industrial raw materials such as rice powder and fruit waste extract (FWE)

Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers

Bearing witness to the Covid-19 lockdown

During the lockdown, migrant workers have produced ‘proofs’ to lay claim to promised aid, display grief and gratitude, and to archive violence they faced. These fragments from the worker-as-witness throw up critical questions on practices of welfare and aid

A Study to Assess the Knowledge and Practice Regarding Cardiopulmonary Resuscitation Among Nursing Students of Agra, Uttarpradesh

Background: Cardiopulmonary resuscitation (CPR) is a life-saving operation performed in an emergency when the heart stops beating. Immediate CPR following a cardiac arrest can double or triple the odds of survival. The American Heart Association welcomes you to join us in our vision of a future without cardiac arrest. In the United States, 350,000 individuals die from cardiac arrest each year. CPR keeps the blood pumping and the body supplied with oxygen until specialized treatment is available. There is normally enough oxygen left in the blood to support the brain and other organs for a few minutes. Objective: To assess the knowledge and practice regarding cardiopulmonary resuscitation among diploma nursing students. Methods: Descriptive research design was used. This study included 60 students. Knowledge and practice checklist was used to assess the knowledge and practice and chi-square test used to see the association between dependent and independent variables. Result: In this study, level of knowledge regarding cardiopulmonary resuscitation pretest level poor knowledge 23(38.3%), poor knowledge 19(31.7%) and good knowledge 18(30%) . level of skills regarding cardiopulmonary resuscitation pretest level skills 60(100%) poor skills 0(0.0%) good skills. Age, Gender, religion, Course of study, Family history of cardiac disease, Aware about cardio pulmonary resuscitation, source of information regarding cardio pulmonary resuscitation, Classes on cardio pulmonary resuscitation within the last 6 months had shown no statistically significant association with the pretest levels of skills regarding cardio pulmonary resuscitation among students. Conclusion: Despite the fact that more than half of students had good knowledge, so students required proper skill development about cardio pulmonary resuscitation

Gendered participation in informal milk markets in Kenya: Implications for low emissions dairy development

Gendered preferences for engagement in informal versus formal milk markets reflect differential ability to benefit from them. In Kenya, married women are likely to lose control over dairy income and decision-making when milk is marketed to formal channels, thus they often opt to sell milk through informal arrangements. Women selling to or working in the informal sector as vendors (“milk hawkers”) are circumventing male-dominated formal structures and increasing their access to income. Low emissions dairy development (LEDD) has been pursued only through the formal milk marketing sector, creating a reifying dilemma for existing power structures in terms of gendered access to dairy income. Both formal and informal market participation provide important avenues towards agency and prosperity for women and their families. Understanding the social trade-offs in market participation for both is necessary to inform to inform gender inclusive low emissions dairy development strategies

Disease signatures are robust across tissues and experiments

Meta-analyses combining gene expression microarray experiments offer new insights into the molecular pathophysiology of disease not evident from individual experiments. Although the established technical reproducibility of microarrays serves as a basis for meta-analysis, pathophysiological reproducibility across experiments is not well established. In this study, we carried out a large-scale analysis of disease-associated experiments obtained from NCBI GEO, and evaluated their concordance across a broad range of diseases and tissue types. On evaluating 429 experiments, representing 238 diseases and 122 tissues from 8435 microarrays, we find evidence for a general, pathophysiological concordance between experiments measuring the same disease condition. Furthermore, we find that the molecular signature of disease across tissues is overall more prominent than the signature of tissue expression across diseases. The results offer new insight into the quality of public microarray data using pathophysiological metrics, and support new directions in meta-analysis that include characterization of the commonalities of disease irrespective of tissue, as well as the creation of multi-tissue systems models of disease pathology using public data