Scavenger receptor B1 facilitates the endocytosis of Escherichia coli via TLR4 signaling in mammary gland infection.

SCARB1 belongs to class B of Scavenger receptors (SRs) that are known to be involved in binding and endocytosis of various pathogens. SRs have emerging role in regulating innate immunity and host-pathogen interactions by acting in co-ordination with Toll-like receptors.Query Little is known about the function of SCARB1 in milk-derived mammary epithelial cells (MECs). This study reports the role of SCARB1 in infection and its potential association in TLR4 signaling on bacterial challenge in Goat mammary epithelial cells (GMECs). The novelty in the establishment of MEC culture lies in the method that aims to enhance the viability of the cells with intact characteristics upto a higher passage number. We represent MEC culture to be used as a potential infection model for deeper understanding of animal physiology especially around the mammary gland. On E.coli challenge the expression of SCARB1 was significant in induced GMECs at 6 h. Endoribonuclease-esiRNA based silencing of SCARB1 affects the expression of TLR4 and its pathways i.e. MyD88 and TRIF pathways on infection. Knockdown also affected the endocytosis of E.coli in GMECs demonstrating that E.coli uses SCARB1 function to gain entry in cells. Furthermore, we predict 3 unique protein structures of uncharacterized SCARB1 (Capra hircus) protein. Overall, we highlight SCARB1 as a main participant in host defence and its function in antibacterial advances to check mammary gland infections. Video Abstract.

Morphometric indices of native sheep breeds of the Himalayan region of India using multivariate principal component analysis.

This study was performed to analyze the morphometric traits and indices in 3000 animals of five registered sheep breeds in the Himalayan region under a multivariate approach. Data were recorded under field conditions with equal coverage of the five breeds, viz., Karnah, Gurez, Poonchi, Bakerwal and Changthangi on body length (BL), height at withers (HW), chest girth (CG), ear length (EL), and tail length (TL). Furthermore, four derived traits (indices) were studied, which included an index of body frame (IBF), an index of thorax development (ITD), a Baron-Crevat index (BCI), and an index of body weight (IBW). Multivariate principal component analysis (PCA) was undertaken on nine morphometric traits. Kaiser's criterion was used to reduce the number of principal components for further analysis and interpretation. The adequacy of sampling was evaluated using Kaiser-Meyer-Olkin (KMO) test and Bartlett's test of sphericity. The mean BL ranged from 52.15 (Changthangi) to 71.13 (Gurez). The estimates of HW, CG, EL and TL were highest in Gurez (63.49), Bakerwal (84.82), Bakerwal (7.26), and Karnah (8.18) breeds, respectively. Among the derived traits, the highest IBF was observed in the Gurez breed with an estimate of 112.22. Upon multivariate PCA on the dataset, the first four principal components were able to explain 92.117% of the total variance. The KMO test, Bartlett's test of sphericity and estimated communalities showed the appropriateness of PCA on the evaluated traits. Four eigenvalues were greater than one and were extracted for further analysis. Morphometric traits were highly correlated, except for EL and TL that showed lower correlation estimates with other traits. The Changthangi population showed the lowest estimates of BL, HW, CG and rectangular body frame. The present study ascertained important morphometric traits/indices that can help in developing selection criteria and formulating sustainable breeding and conservation plans vis-à-vis the unique sheep breeds of the temperate Himalayas.

Comparative RNA-Seq analysis reveals insights in Salmonella disease resistance of chicken; and database development as resource for gene expression in poultry.

Salmonella, one of the major infectious diseases in poultry, causes considerable economic losses in terms of mortality and morbidity, especially in countries that lack effective vaccination programs. Besides being resistant to diseases, indigenous chicken breeds are also a potential source of animal protein in developing countries. For understanding the disease resistance, an indigenous chicken line Kashmir faverolla, and commercial broiler were selected. RNA-seq was performed after challenging the chicken with Salmonella Typhimurium. Comparative differential expression results showed that following infection, a total of 3153 genes and 1787 genes were differentially expressed in the liver and spleen, respectively. The genes that were differentially expressed included interleukins, cytokines, NOS2, Avß-defensins, toll-like receptors, and other immune-related gene families. Most of the genes and signaling pathways involved in the innate and adaptive immune responses against bacterial infection were significantly enriched in the Kashmir faverolla. Pathway analysis revealed that most of the enriched pathways were MAPK signaling pathway, NOD-like receptor signaling pathway, TLR signaling pathway, PPAR signaling pathway, endocytosis, etc. Surprisingly some immune-related genes like TLRs were upregulated in the susceptible chicken breed. On postmortem examination, the resistant birds showed small lesions in the liver compared to large necrotic lesions in susceptible birds. The pathological manifestations and RNA sequencing results suggest a balancing link between resistance and infection tolerance in Kashmir faverolla. Here we also developed an online Poultry Infection Database (https://skuastk.org/pif/index.html), the first publicly available gene expression resource for disease resistance in chickens. The available database not only shows the data for gene expression in chicken tissues but also provides quick search, visualization and download capacity.

Climate plays a dominant role over land management in governing soil carbon dynamics in North Western Himalayas.

The soil carbon (C) dynamics is strongly influenced by climate and land-use patterns in the Himalayas. Therefore, soils under five prominent land use [e.g., maize (Zea mays), horticulture, natural forest, grassland, and wasteland] were sampled down up to 30 cm depth under two climatic conditions viz., temperate and subtropical to assess the impacts of climate and landuse on soil C dynamics. Results demonstrated that irrespective of land use, temperate soil contains 30.66% higher C than subtropical soils. Temperate soils under natural forests had the higher total organic carbon (TOC, 21.90 g kg-1), Walkley-Black carbon (WBC, 16.42 g kg-1), contents, and stocks (TOC, 66.92 Mg ha-1 and WBC, 50.24 Mg ha-1), and total soil organic matter (TSOM, 3.78%) concentration as compared to other land uses like maize, horticulture, grassland, and wasteland. Under both climatic conditions, maize land use had the lowest TOC 9.63, 6.55 g kg-1 and WBC 7.22, 4.91 g kg-1 at 0-15 and 15-30 cm soil depth, respectively. Horticulture land use had 62.58 and 62.61% higher TOC and WBC over maize-based land use under subtropical and temperate climatic conditions at 0-30 cm soil depth, respectively. However, soils of maize land use under temperate conditions had ∼2 times more TOC than in subtropical conditions. The study inferred that the C-losses is more in the subtropical soil than in temperate soils. Hence, the subtropical region needs more rigorous adoption of C conservation farming practices than the temperate climatic setting. Although, the adoption of C storing and conserving practices is crucial under both climatic settings to arrest land degradation. Horticultural land uses along with conservation effective soil management practices may be encouraged to restore more soil C and to improve the livelihood security of the hill populace in the North Western Himalayas.

Comparison of various models for the estimation of heritability and breeding values.

The exploration of additive genetic variance for the selection of animals is the central paradigm in quantitative genetics and it is important to use appropriate animal models considering important factors. This study compares various factor effects for heritability and breeding values estimations on data collected on the Corriedale. Overall, the heritability estimates were the highest for birthweight (BW). Both the additive genetic variance and the heritability values were reduced upon adding more random effects. Year-effect as random reduced the heritability except for BW. The highest average accuracy for breeding values for birth, weaning, 6, 9, and 12-month-weights for were 0.656, 0.567, 0.519, 0.486, and 0.515. These were observed for models having sex or sex and parity as fixed effects. It is concluded that fixed and random factors have a significant impact on genetic-factors and breeding-value accuracies and should be considered during selection programs and make the selection program more effective.

Mammary epithelial cell transcriptome reveals potential roles of lncRNAs in regulating milk synthesis pathways in Jersey and Kashmiri cattle.

BACKGROUND: Long noncoding RNAs (lncRNAs) are now proven as essential regulatory elements, playing diverse roles in many biological processes including mammary gland development. However, little is known about their roles in the bovine lactation process. RESULTS: To identify and characterize the roles of lncRNAs in bovine lactation, high throughput RNA sequencing data from Jersey (high milk yield producer), and Kashmiri cattle (low milk yield producer) were utilized. Transcriptome data from three Kashmiri and three Jersey cattle throughout their lactation stages were utilized for differential expression analysis. At each stage (early, mid and late) three samples were taken from each breed. A total of 45 differentially expressed lncRNAs were identified between the three stages of lactation. The differentially expressed lncRNAs were found co-expressed with genes involved in the milk synthesis processes such as GPAM, LPL, and ABCG2 indicating their potential regulatory effects on milk quality genes. KEGG pathways analysis of potential cis and trans target genes of differentially expressed lncRNAs indicated that 27 and 48 pathways were significantly enriched between the three stages of lactation in Kashmiri and Jersey respectively, including mTOR signaling, PI3K-Akt signaling, and RAP1 signaling pathways. These pathways are known to play key roles in lactation biology and mammary gland development. CONCLUSIONS: Expression profiles of lncRNAs across different lactation stages in Jersey and Kashmiri cattle provide a valuable resource for the study of the regulatory mechanisms involved in the lactation process as well as facilitate understanding of the role of lncRNAs in bovine lactation biology.

Comparative transcriptomics unravels new genes imparting scab resistance in apple (Malus x domestica Borkh.).

Apple scab is caused by an ascomycete fungus, Venturia inaequalis (Cke.) Wint., which is one of the most severe disease of apple (Malus × Domestica Borkh.) worldwide. The disease results in 30-40% fruit loss annually and even complete loss in some places. Owing to the evolving susceptibility of resistant apple genotypes harboring R-genes to new variants of V. inaequalis, a comparative transcriptome analysis using Illumina (HiSeq) platform of three scab-resistant (Florina, Prima, and White Dotted Red) and three susceptible (Ambri, Vista Bella, and Red Delicious) apple genotypes was carried out to mine new scab resistance genes. The study led to the identification of 822 differentially expressed genes in the tested scab-resistant and scab-susceptible apple genotypes. The most upregulated genes uniformly expressed in resistant varieties compared to susceptible ones were those coding for 17.3 kDa class II heat shock protein-like, chaperone protein ClpB1, glutathione S-transferase L3-like protein, B3 domain-containing protein At3g18960-like, transcription factor bHLH7, zinc finger MYM-type protein 1-like, and nine uncharacterized proteins, besides three lncRNAs. The genes that were downregulated in susceptible and upregulated in resistant cultivars were those coding for non-specific lipid transfer protein GPI-anchored 1, rust resistance kinase Lr10-like, disease resistance protein RPS6-like, and many uncharacterized proteins. DESeq2 analysis too revealed 20 DEGs that were upregulated in scab-resistant cultivars. Furthermore, a total of 361 genes were significantly upregulated in scab-susceptible variety, while 461 were found downregulated (P value < 0.05 and Log2 (FC) > 1). The differentially expressed genes (DEGs) were related to various pathways, i.e., metabolic, protein processing, biosynthesis of secondary metabolites, plant hormone signal transduction, autophagy, ubiquitin-mediated proteolysis, plant-pathogen interaction, lipid metabolism, and protein modification pathways. Real-time expression of a set of selected twelve DEGs further validated the results obtained from RNA-seq. Overall, these findings lay the foundation for investigating the genetic basis of apple scab resistance and defense pathways that might have a plausible role in governing scab resistance in apple against V. inaequalis.

Expression of lncRNAs in response to bacterial infections of goat mammary epithelial cells reveals insights into mammary gland diseases.

Mastitis or inflammation of the mammary gland is a highly economic and deadly alarming disease for the dairy sector as well as policymakers caused by microbial infection. Transcriptomic and proteomic approaches have been widely employed to identify the underlying molecular mechanisms of bacterial infections in the mammary gland. Numerous differentially expressed mRNAs, miRNAs, and proteins together with their associated signaling pathways have been identified during bacterial infection, paving the way for analysis of their biological functions. Long noncoding RNAs (lncRNAs) are important regulators of multiple biological processes. However, little is known regarding their role in bacterial infection in mammary epithelial cells. Hence, RNA-sequencing was performed by infecting primary mammary epithelial cells (pMECs) with both gram-negative (E. coli) and gram-positive bacteria (S. aureus). Using stringent pipeline, a set of 1957 known and 1175 novel lncRNAs were identified, among which, 112 lncRNAs were found differentially expressed in bacteria challenged PMECs compared with the control. Additionally, potential targets of the lncRNAs were predicted in cis- and trans-configuration. KEGG analysis revealed that DE lncRNAs were associated with at least 15 immune-related pathways. Therefore, our study revealed that bacterial challenge triggers the expression of lncRNAs associated with immune response and defense mechanisms in goat mammary epithelial cells.

Evaluation of the nutritional value of faba beans with high and low tannin content for use as feed for ruminants.

BACKGROUND: Faba bean varieties with low or zero tannin content have been developed in Canada to overcome the negative effects of condensed tannins on the utilization by ruminants of crude protein (CP) and starch. However, their nutritional value has not been evaluated for incorporation in dairy rations. The objectives of this study were to investigate (i) the chemical profile; (ii) the Cornell Net Carbohydrate and Protein System (CNCPS) protein and carbohydrate subfractions; (iii) the energy values; (iv) the ruminal, intestinal, and total digestibility of CP; (v) the metabolizable protein (MP) supply to dairy cows; and (vi) the protein-inherent molecular spectral characteristics of brown-seeded (var. Fatima) faba beans with high tannin content and yellow-seeded (var. Snowbird) faba beans with low tannin content. RESULTS: The results revealed that Fatima beans had higher (P < 0.001) CP content than Snowbird (324 versus 295 g kg-1 dry matter (DM)), and lower (P < 0.01) starch content than Snowbird (411 g kg-1 DM versus 444 g kg-1 DM). Fatima had a lower (P = 0.001) soluble subfraction (201 g kg-1 DM versus 220 g kg-1 DM) and higher (P < 0.05) slowly degradable fiber-bounded (24.9 g kg-1 DM versus 14.7 g kg-1 DM) and non-degradable (3.24 g kg-1 DM versus 0 g kg-1 DM) CNCPS CP subfractions than Snowbird. Fatima had higher (P = 0.03) MP content (117 g kg-1 DM versus 111 g kg-1 DM) and metabolizable energy content (ME) 3.12 Mcal kg-1 versus 3.10 Mcal kg-1 ) than Snowbird. Molecular spectral intensities of amide I and II proteins (height and area) of Fatima were higher (P < 0.05) than those of Snowbird, reflecting their higher CP content. The ratio of protein spectral intensities, the amide I : amide II height ratio, and the α-helix : ß-sheet height ratio differed (P < 0.05) between the two types of bean, highlighting differences in their inherent protein molecular structures. CONCLUSION: The (Fatima) faba beans with high condensed tannin content had higher MP and ME content. On average, both Faba beans had higher ME and MP content than barley grains, highlighting their promising nutritional value for dairy rations. © 2021 Society of Chemical Industry.

Improving the nutritional value and digestibility of wheat straw, rice straw, and corn cob through solid state fermentation using different Pleurotus species.

BACKGROUND: The growing food-feed-fuel competition, declining availability of traditional feeds, higher prices, and the urgent need to provide long-term sustainability for animal production have all triggered global research into the optimum extraction of energy and nutrients from lignin-rich plant biomass. Recent studies have shown that the Pleurotus species of white rot fungus can selectively degrade lignin in lignin-rich plant biomass; however, its effectiveness in selectively degrading lignin depends on the type of substrate and species of fungus. This study was therefore designed to treat wheat straw, rice straw, and corn cob, with Pleurotus eryngii, P. ostreatus, and P. florida for 30 days under solid-state fermentation, to identify a promising fungus-substrate combination for the selective degradation of lignin and optimal improvement in the nutritional value and digestibility of each substrate. RESULTS: The type of fungus strongly influenced (P < 0.01) selectivity in lignin degradation, and the level of improvement in crude protein (CP), in vitro dry matter digestibility (IVDMD), and in vitro gas production (IVGP), in wheat straw, rice straw, and corn cob. Fungus-substrate interaction data revealed that P. ostreatus caused maximum (P < 0.05) degradation of lignin, and greater (P < 0.05) improvement in CP, IVDMD, and IVGP in wheat straw and rice straw. The lowest (P < 0.05) degradation of lignin and improvement in CP, IVDMD, and IVGP was caused by P. eryngii in corn cob. Among the fungi, the maximum (P < 0.05) degradation of lignin, and greater (P < 0.05) improvement in CP, IVDMD, and IVGP were caused by P. florida as compared with those of P. ostreatus and P. eryngii. CONCLUSION: The results highlight significant influence of fungus-substrate combination for selective lignin degradability and the consequent improvement in the nutritional value of the substrates. Maximum selective lignin degradability and improvement in nutritional value and digestibility was caused by P. ostreatus in wheat straw and in rice straw, and by P. florida in corn cob. © 2021 Society of Chemical Industry.

Effectiveness and Cardiac Safety of Bedaquiline-Based Therapy for Drug-Resistant Tuberculosis: A Prospective Cohort Study.

BACKGROUND: Bedaquiline improves treatment outcomes in patients with rifampin-resistant (RR) tuberculosis but prolongs the QT interval and carries a black-box warning from the US Food and Drug Administration. The World Health Organization recommends that all patients with RR tuberculosis receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published. METHODS: We conducted an observational cohort study of patients with RR tuberculosis from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, which included obtaining electrocardiograms in triplicate at 4 time points during bedaquiline therapy. Participants were followed up until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT interval prolongation (QT prolongation), defined as any QT interval corrected by the Fridericia method (QTcF) >500 ms or an absolute change from baseline (ΔQTcF) >60 ms. RESULTS: We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant tuberculosis. Most participants (97%) received concurrent clofazimine. Of the participants, 74% were cured or successfully completed treatment, and outcomes did not differ by human immunodeficiency virus status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase (standard deviation) of 23.7 (22.7) ms from baseline to month 6. Four participants experienced a QTcF >500 ms and 19 experienced a ΔQTcF >60 ms. Older age was independently associated with QT prolongation. QT prolongation was neither more common nor more severe in participants receiving concurrent lopinavir-ritonavir. CONCLUSIONS: Severe QT prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close monitoring of the QT interval may be advisable in older patients.

Haematological and serum biochemical reference values of snow trout, Schizothorax labiatus habiting in river Sindh of Indian Himalayan region.

Haematological and serum biochemical parameters are a valuable tool in determining the wellbeing status of different fish species and response in close association to various biological and environmental factors, therefore the aim of the present study was to establish sex-wise reference values of haemato-biochemical parameters of S. labiatus. The haematological parameters such as haemoglobin (Hb) concentration, total erythrocyte count (RBC), total leucocyte count (WBC), packed cell volume (PCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV) and serum biochemical parameters such as glucose, cholesterol, urea, total protein, albumin and globulin were analysed. The results revealed that the haematological parameters, i.e., Hb, RBC, WBC and PCV showed significant (P < 0.05) differences with respect to sex. Significantly (P < 0.05) higher values of Hb content (11.18 g dl-1 ), RBC count (1.88 × 106 mm-3 ) and PCV (36.15%) were noted in male fish than females throughout the study period, while significantly (P < 0.05) higher WBC count was noted in females (20.38 × 103 mm-3 ) compared to males. However, no significant (P > 0.05) difference was observed in erythrocyte indices like MCH, MCHC and MCV between sexes. The serum biochemical parameters, i.e., glucose, cholesterol and urea, also showed significant (P < 0.05) difference between the sexes, but no significant (P > 0.05) difference was noticed in total protein, albumin and globulin. Significantly (P < 0.05) highest values of glucose (116.76 mg dl-1 ) and urea (9.01 mg dl-1 ) were recorded in male S. labiatus, while highest value of cholesterol (223.53 mg dl-1 ) was noted in females. The information generated in the present study gives the basic reference values of haematological and serum biochemical parameters of S. labiatus which will be useful in monitoring the wellbeing status of fish populations. Moreover, the data will also be helpful to ascertain the occurrence of different clinical and subclinical diseases, which may in turn help to boost the overall production of this species.

Cryptococcal-related Mortality Despite Fluconazole Preemptive Treatment in a Cryptococcal Antigen Screen-and-Treat Program.

BACKGROUND: Cryptococcal antigen (CrAg) screening and treatment with preemptive fluconazole reduces the incidence of clinically evident cryptococcal meningitis in individuals living with advanced human immunodeficiency virus (HIV) disease. However, mortality remains higher in CrAg-positive than in CrAg-negative patients with similar CD4+ T-lymphocyte counts. METHODS: We conducted a cohort study to investigate causes of morbidity and mortality during 6 months of follow-up among asymptomatic CrAg-positive and CrAg-negative (ratio of 1:2) patients living with HIV with CD4 counts <100 cells/µL attending 2 hospitals in Johannesburg, South Africa. When possible, minimally invasive autopsy (MIA) was performed on participants who died. RESULTS: Sixty-seven CrAg-positive and 134 CrAg-negative patients were enrolled. Death occurred in 17/67 (25%) CrAg-positive and 12/134 (9%) CrAg-negative participants (hazard ratio for death, adjusted for CD4 count, 3.0; 95% confidence interval, 1.4-6.7; P = .006). Cryptococcal disease was an immediate or contributing cause of death in 12/17 (71%) CrAg-positive participants. Postmortem cryptococcal meningitis and pulmonary cryptococcosis were identified at MIA in all 4 CrAg-positive participants, 3 of whom had negative cerebrospinal fluid CrAg tests from lumbar punctures (LPs) at the time of CrAg screening. CONCLUSIONS: Cryptococcal disease was an important cause of mortality among asymptomatic CrAg-positive participants despite LPs to identify and treat those with subclinical cryptococcal meningitis and preemptive fluconazole for those without meningitis. Thorough investigation for cryptococcal disease with LPs and blood cultures, prompt ART initiation, and more intensive antifungals may reduce mortality among asymptomatic CrAg-positive patients identified through screening.

Comparative milk proteome analysis of Kashmiri and Jersey cattle identifies differential expression of key proteins involved in immune system regulation and milk quality.

BACKGROUND: Exploration of the bioactive components of bovine milk has gained global interest due to their potential applications in human nutrition and health promotion. Despite advances in proteomics profiling, limited studies have been carried out to fully characterize the bovine milk proteome. This study explored the milk proteome of Jersey and Kashmiri cattle at day 90 of lactation using high-resolution mass spectrometry based quantitative proteomics nano-scale LC-MS/Q-TOF technique. Data are available via ProteomeXchange with identifier PXD017412. RESULTS: Proteins from whey were fractionated by precipitation into high and low abundant proteins. A total of 81 high-abundant and 99 low-abundant proteins were significantly differentially expressed between Kashmiri and Jersey cattle, clearly differentiating the two breeds at the proteome level. Among the top differentiating proteins, the Kashmiri cattle milk proteome was characterised by increased concentrations of immune-related proteins (apelin, acid glycoprotein, CD14 antigen), neonatal developmental protein (probetacellulin), xenobiotic metabolising enzyme (flavin monooxygenase 3 (FMO3), GLYCAM1 and HSP90AA1 (chaperone) while the Jersey milk proteome presented higher concentrations of enzyme modulators (SERPINA1, RAC1, serine peptidase inhibitor) and hydrolases (LTF, LPL, CYM, PNLIPRP2). Pathway analysis in Kashmiri cattle revealed enrichment of key pathways involved in the regulation of mammary gland development like Wnt signalling pathway, EGF receptor signalling pathway and FGF signalling pathway while a pathway (T-cell activation pathway) associated with immune system regulation was significantly enriched in Jersey cattle. Most importantly, the high-abundant FMO3 enzyme with an observed 17-fold higher expression in Kashmiri cattle milk seems to be a characteristic feature of the breed. The presence of this (FMO3) bioactive peptide/enzyme in Kashmiri cattle could be economically advantageous for milk products from Kashmiri cattle. CONCLUSION: In conclusion, this is the first study to provide insights not only into the milk proteome differences between Kashmiri and Jersey cattle but also provides potential directions for application of specific milk proteins from Kashmiri cattle in special milk preparations like infant formula.

CO2 utilization: Turning greenhouse gas into fuels and valuable products.

This study critically reviews the recent developments and future opportunities pertinent to the conversion of CO2 as a potent greenhouse gas (GHG) to fuels and valuable products. CO2 emissions have reached an alarming level of around 410 ppm and have become the primary driver of global warming and climate change leading to devastating events such as droughts, hurricanes, torrential rains, floods, tornados and wildfires across the world. These events are responsible for thousands of deaths and have adversely affected the economic development of many countries, loss of billions of dollars, across the globe. One of the promising choices to tackle this issue is carbon sequestration by pre- and post-combustion processes and oxyfuel combustion. The captured CO2 can be converted into fuels and valuable products, including methanol, dimethyl ether (DME), and methane (CH4). The efficient use of the sequestered CO2 for the desalinization might be critical in overcoming water scarcity and energy issues in developing countries. Using the sequestered CO2 to produce algae in combination with wastewater, and producing biofuels is among the promising strategies. Many methods, like direct combustion, fermentation, transesterification, pyrolysis, anaerobic digestion (AD), and gasification, can be used for the conversion of algae into biofuel. Direct air capturing (DAC) is another productive technique for absorbing CO2 from the atmosphere and converting it into various useful energy resources like CH4. These methods can effectively tackle the issues of climate change, water security, and energy crises. However, future research is required to make these conversion methods cost-effective and commercially applicable.

Clofazimine Exposure In Vitro Selects Efflux Pump Mutants and Bedaquiline Resistance.

Six in vitro clofazimine-resistant spontaneous mutants obtained from a wild-type or pyrazinamide-resistant ATCC reference strain were selected to evaluate bedaquiline cross-resistance. The reverse was conducted for bedaquiline mutants. All clofazimine mutants harboring an rv0678 mutation displayed phenotypic cross-resistance. We observed the same for rv0678 bedaquiline mutants; however, atpE bedaquiline mutants showed no phenotypic cross-resistance. This confirms that upfront clofazimine usage may impact subsequent bedaquiline use due to a shared efflux resistance pathway.

In Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline Resistance.

Bedaquiline resistance within Mycobacterium tuberculosis may arise through efflux-based (rv0678) or target-based (atpE) pathway mutations. M. tuberculosis mutant populations from each of five sequential steps in a passaging approach, using a pyrazinamide-resistant ATCC strain, were subjected to MIC determinations and whole-genome sequencing. Exposure to increasing bedaquiline concentrations resulted in increasing phenotypic resistance (up to >2 µg/ml) through MIC determination on solid medium (Middlebrook 7H10). rv0678 mutations were dynamic, while atpE mutations were fixed, once occurring. We present the following hypothesis for in vitro emergence of bedaquiline resistance: rv0678 mutations may be the first transient step in low-level resistance acquisition, followed by high-level resistance due to fixed atpE mutations.

ABC of multifaceted dystrophin glycoprotein complex (DGC).

Dystrophin protein in association with several other cellular proteins and glycoproteins leads to the formation of a large multifaceted protein complex at the cell membrane referred to as dystrophin glycoprotein complex (DGC), that serves distinct functions in cell signaling and maintaining the membrane stability as well as integrity. In accordance with this, several findings suggest exquisite role of DGC in signaling pathways associated with cell development and/or maintenance of homeostasis. In the present review, we summarize the established facts about the various components of this complex with emphasis on recent insights into specific contribution of the DGC in cell signaling at the membrane. We have also discussed the recent advances made in exploring the molecular associations of DGC components within the cells and the functional implications of these interactions. Our review would help to comprehend the composition, role, and functioning of DGC and may lead to a deeper understanding of its role in several human diseases.