Effect of the global electroneutrality condition on electromigration Taylor-Aris dispersion in a microcapillary with finite Debye layer thickness.

In this work, the electromigration dispersion (EMD) due to the charged electrolytes in microchannels is considered without using the thin electrical double layer assumption. The electrokinetic flow and transport of ions are actuated within a rectangular micro-/nanochannel having a negative surface charge density under the influence of an external electric field. Due to the local variation of the conductivity and the nonvalidity of the electroneutrality condition, the local electric field varies as a function of the solute concentration, wall surface charge density, valency, and Debye layer length. The resulting electrokinetic flow due to the external electric field drives the fluid along with the charged species, where the Taylor-Aris dispersion separates the solutes into their different constituents. The local concentration dependence of the electric field leads to the formation of concentration profiles that are slightly asymmetric with respect to the standard Gaussian distribution. Including a finite Debye layer thickness has an effect on the advection of the species as well as the diffusion of the species. It is found that in cases where Debye layers are thicker, the species advects faster within the microchannel. This might give valuable insights into the nature of the EMD. Our model aims to predict the evolution of ionic concentration at all positions within the channel. A study of the higher-order statistics in skewness and kurtosis has also been conducted to obtain a better understanding of the idealized model consisting of a buffer solution.

Rice-based integrated farming system improves the soil quality, bacterial community structure and system productivity under sub-humid tropical condition.

Rice-based integrated farming system improves the productivity and profitability by recycling resources efficiently. In the sub-humid tropics, rice production without sufficient nutrient replenishment often leads to soil health and fertility degradation. There has been very limited research on soil health and fertility after adopting a multi-enterprising rice-based integrated farming system (IFS), notably in the rice-fish-livestock and agroforestry system, when compared to a conventional farming system (CS). Therefore, the present study analyzed the dynamics of soil properties, soil bacterial community structure and their possible interaction mechanisms, as well as their effect on regulating soil quality and production in IFS, IFSw (water stagnant area of IFS) and CS. The results indicated that soil nutrient dynamics, bacterial diversity indices (Shannon index, Simpson index, Chao 1, ACE and Fisher index) and system productivity were higher in IFSw and IFS compared to CS. Moreover, relative operational taxonomic units of dominant bacterial genera (Chloroflexi, Acidobacteria, Verrucomicrobia, Planctomycetes, Cyanobacteria, Crenarchaeota and Gemmatimonadetes) were also higher in IFSw and IFS compared to CS. Mean soil quality index (SQI) was highest in IFSw (0.780 ± 0.201) followed by IFS (0.770 ± 0.080) and CS (0.595 ± 0.244). Moreover, rice equivalent yields (REY) and rice yields were well correlated with the higher levels of soil biological indices (SQIBiol) in IFS. Overall, our results revealed that rice-based IFS improved the soil health and fertility and ensuing crop productivity through positive interaction with soil bacterial communities and nutrient stoichiometry leading to agroecosystem sustainability.

Impact of long-term resource conservation techniques on biogeochemical characteristics and biological soil quality indicators in a rice green-gram farming system.

Nutrient management in resource conservation practices influence the structural and functional microbial diversities and thereby affect biological processes and biochemical properties in soil. We studied the long-term effects of resource conservation technologies on functional microbial diversity and their interactions with soil biochemical properties and enzymatic activities in tropical rice-green gram cropping system. The experiment includes seven treatments viz., conventional practice (CC), brown manuring (BM), green manuring (GM), wet direct drum sowing, zero tillage, green manuring-customized leaf colour chart based-N application (GM-CLCC-N) and biochar (BC) application. The result of the present study revealed that microbial biomass nitrogen (N), carbon (C) and phosphorus (P) in GM practice were increased by 23.3, 37.7 and 35.1%, respectively than CC. GM, BM and GM-CLCC-N treatments provide higher yields than conventional practice. The average well color development value, Shannon index and McIntosh index were significantly higher by 26.6%, 86.9% and 29.2% in GM as compared to control treatment. So, from this study we can conclude that resource conservation practices like GM, GM-CLCC N and BM in combination with chemical fertilizers provide easily decomposable carbon source to support the microbial growth. Moreover, dominance of microbial activity in biomass amended treatments (GM, GM-CLCC N and BM) indicated that these treatments could supply good amount of labile C sources on real time basis for microbial growth that may protect the stable C fraction in soil, hence could support higher yield and soil organic carbon build-up in long run under rice-green gram soil.

Rhino-orbito-cerebral mucormycosis: patient characteristics in pre-COVID-19 and COVID-19 period.

BACKGROUND: Rhino-orbito-cerebral-mucormycosis (ROCM), a rare and potentially fatal disease was seen in increasing numbers during the COVID-19 pandemic. This study describes and compares the patient characteristics and outcomes in COVID-19 associated mucormycosis (CAM) and non-COVID-19 mucormycosis (non-CAM). METHODOLOGY: CAM patients (24 cases) were recruited from the COVID-19 period and non-CAM (24 controls) from the pre-COVID-19 period. Clinical data of the CAM group was collected retrospectively with 3 month outcomes prospectively. The non-CAM group data was collected retrospectively. Patient characteristics were compared and risk factors for mortality in ROCM were assessed. RESULTS: Orbital symptoms [altered vision, restricted eye movements, ptosis] and intracranial involvement were higher in CAM patients on presentation. Similarly, the radiological involvement of orbit (orbital apex, superior orbital fissure) and intracranial cavity (intracranial thrombosis, cavernous sinus) was also higher in CAM patients. Newly detected diabetes was found only in CAM patients (29.2%). Although univariate analysis suggested an increased mortality risk in ROCM patients with orbital involvement, the multivariate analysis showed no increased risk with any of the parameters assessed, including COVID-19 positivity. CONCLUSIONS: Compared to the non-CAM, the disease presentation was severe in CAM with higher frequency of orbital and intracranial involvement. However, with early detection and treatment, the short term survival was comparable in both groups.

Homology modeling and virtual characterization of cytochrome c nitrite reductase (NrfA) in three model bacteria responsible for short-circuit pathway, DNRA in the terrestrial nitrogen cycle.

NrfA is the molecular marker for dissimilatory nitrate reduction to ammonium (DNRA) activity, catalysing cytochrome c nitrite reductase enzyme. However, the limited study has been made so far to understand the structural homology modeling of NrfA protein in DNRA bacteria. Therefore, three model DNRA bacteria (Escherechia coli, Wolinella succinogenes and Shewanella oneidensis) were chosen in this study for in-silico protein modeling of NrfA which roughly consists of similar length of amino acids and molecular weight and they belong to two contrasting taxonomic families (γ-proteobacteria with nrfABCDEFG and ε-proteobacteria with nrfHAIJ operon). Multiple bioinformatic tools were used to examine the primary, secondary, and tertiary structure of NrfA protein using three distinct homology modeling pipelines viz., Phyre2, Swiss model and Modeller. The results indicated that NrfA protein in E. coli, W. succinogenes and S. oneidensis was mostly periplasmic and hydrophilic. Four conserved Cys-X1-X2-Cys-His motifs, one Cys-X1-X2-Cys-Lys haem-binding motif and Ca ligand were also identified in NrfA protein irrespective of three model bacteria. Moreover, 11 identical conserved amino acids sequence was observed for the first time between serine and proline in NrfA protein. Secondary structure of NrfA revealed that α-helices were observed in 77.9%, 73.4%, and 77.4% in E. coli, W. succinogenes and S. oneidensis, respectively. Ramachandran plot showed that number of residue in favored region in E. coli, W. succinogenes and S. oneidensis was 97.03%, 97.01% and 97.25%, respectively. Our findings also revealed that among three pipelines, Modeller was considered the best in-silico tool for prediction of NrfA protein. Overall, significant findings of this study may aid in the identification of future unexplored DNRA bacteria containing cytochrome c nitrite reductase. The NrfA system, which is linked to respiratory nitrite ammonification, provides an analogous target for monitoring less studied N-retention processes, particularly in agricultural ecosystems. Furthermore, one of the challenging research tasks for the future is to determine how the NrfA protein responds to redox status in the microbial cells.

High-Order Phase-Dependent Asymmetry in the Above-Threshold Ionization Plateau.

Above-threshold ionization spectra from cesium are measured as a function of the carrier-envelope phase (CEP) using laser pulses centered at 3.1 µm wavelength. The directional asymmetry in the energy spectra of backscattered electrons oscillates three times, rather than once, as the CEP is changed from 0 to 2π. Using the improved strong-field approximation, we show that the unusual behavior arises from the interference of few quantum orbits. We discuss the conditions for observing the high-order CEP dependence, and draw an analogy with time-domain holography with electron wave packets.

Maternal anthropometric determinants as risk markers of suicidality and severity of illness in women with postnatal depression.

Context: Studies have shown nutrition to play a role in etiology of postnatal depression, but few risk markers have been developed for the same. Anthropometric determinants have not been sufficiently researched in relation to suicidality and severity of illness in women with postnatal depression. Aim: The present study assesses the efficacy of anthropometric determinants as risk markers of severity of illness and suicidal ideations in postnatal depression. Methods and Materials: 100 women were screened at 6 weeks postnatal for the presence of postnatal depression and suicidal ideation using the Edinburgh Postnatal Depression Scale. Anthropometric determinants assessed were height, weight, weight gain in pregnancy, weight at first antenatal visit, body mass index and waist-to-hip ratio. Univariate and multivariate analysis were done for risk estimation using Spearman's rank correlation and multiple regression analysis, respectively. Results: In total, 39% of the women showed the presence of postnatal depression. Out of these 39 women, 31% had suicidal ideations. The waist-to-hip ratio was the most significant factor in all the models, having a negative correlation with suicidality and severity of depression (P < 0.05). The multiple regression model using anthropometric determinants could significantly assess risk of both suicidality (P = 0.03, adjusted R2 = 0.08) and postnatal depression (P = 0.04, adjusted R2 = 0.07). Conclusions: The study concludes that anthropometric determinants can be used effectively as risk markers for suicidality and severity of illness in women with postnatal depression. The most significant risk factor was found to be waist-to-hip ratio in both the models.

Non-target effect of bispyribac sodium on soil microbial community in paddy soil.

Bispyribac sodium is frequently used herbicide in the rice field. Though, it has been targeted to kill rice weeds, but its non-target effect on soil microbes in paddy soil was largely unknown. Therefore, in the present study, an attempt was made to assess the non-target effect of bispyribac sodium on alteration of functional variation of soil microbial community and their correlation with microbial biomass carbon (MBC) and soil enzymes. A microcosm experiment set up was made comprising three treatments viz., control (CON) (without application of bispyribac sodium), recommended dose of bispyribac sodium (35 g ha-1) (BS), and double the dose of BS (70 g ha-1) (DBS). Results indicated that the MBC and soil enzyme activities (dehydrogenase, alkaline phosphatase and urease) in BS and DBS-treated soil were significantly (p < 0.05) declined from 1st to 30th day after application as compared to CON. Counts of heterotrophic bacteria, actinomycetes and fungal population were also decreased in BS and DBS-treated soil. The average well color development (AWCD) values derived from Biolog®ecoplates followed the order of DBS ˂ BS ˂ CON. Shannon index value was high (p ≤ 0.05) in CON compared to soil-treated with BS and DBS. Principal component analysis (PCA) showed a clear distinction of the cluster of treatments between CON, BS and DBS. Biplot analysis and heatmap suggested that carboxylic compounds and amino acids showed positive response towards BS-treated soil, whereas phenolic compounds had positive correlation with DBS-treated soil. PCA analysis indicated that oligotrophs was rich in BS-treated paddy soil, whereas copiotrophs and asymbiotic nitrogen fixers were richer in DBS treatment. Overall, the present study revealed that application of recommended dose of BS and its double dose alter the soil microbial population, enzyme activities and functional microbial diversity in paddy soil.

Role of Early Referral and Surgical Intervention in Brachial Plexus Birth Palsy: Awareness Among Obstetricians and Pediatricians in a Teaching Hospital.

A cross-sectional study was conducted using a validated and standardized questionnaire answered by willing pediatricians and obstetricians at our university teaching hospitals. Nearly two thirds of the pediatricians (62.8%) and three fourths of the obstetricians (73.6%) continued to accept the terminology of obstetric brachial plexus birth palsy which is a misnomer; 32.6% of pediatricians felt that they were unaware of the current trends in its management. Parental reluctance (23.5%) and inadequate knowledge in current approaches among surgeons and pediatricians (41.2%) were suggested as chief causes for the delay in their adequate referral and management using surgical exploration, nerve grafting, and nerve transfer. The delayed presentations of birth brachial plexus injuries with missed opportunity for optimum treatment can be partly attributed to inadequate information available on definitive guidelines in its management among the stakeholders including parents, primary care physicians, and surgeons.

Inter-relationship between intercepted radiation and rice yield influenced by transplanting time, method, and variety.

Photosynthetically active radiation (PAR) is one of the most important environmental factors that determine the productivity and grain quality of the crops. Continuous rainy days or cloudy weather throughout crop growth especially at critical stages often resulted in great loss of grain quality and yield in rice. Low light stress has rigorously constrained the rice production in various rice-growing regions, especially in Southeast Asia. Method and time of planting are the major management factors contributing to the higher yield potential of rice by influencing light harvesting and use efficiency. Present study was executed consecutively for 5 years (kharif seasons of 2012-2016) to determine whether planting time improves the radiation absorption and use efficiency in different duration rice cultivars. We evaluated the difference in plant growth and development leading to yield formation under different planting time which related to radiation incidence and interception. The results of the study revealed that PAR interception depends on morphological characters of cultivars and also with agronomic management such as transplanting time and method. Long duration cultivar intercepted more PAR but interception decreased due to late planting (3rd week of July), whereas short duration cultivars (Naveen) when planted earlier (1st week of June) could not effectively utilize intercepted PAR constraining the biomass accumulation and yield formation. Effect of planting density and crop architecture on PAR absorption was apparent among establishment methods as light interception at crop canopy was highest in the system of rice intensification and lowest in that of wet direct seeding. In general, Pooja as a long duration cultivar intercepted more PAR per day but when compared on same date of planting, the comparative absorption of radiation was 30.6% higher in Naveen. The lower yields in the wet season are attributed mostly to reduction in grain number per panicle or per unit land area, which is a consequence of high spikelet sterility. Grain yield of rice planted in July third week was reduced by 3.8, 12.3, and 6.9% over June first and third week and July first week, respectively, mainly due to spikelet sterility (26%) and lower grains per panicle (18%). Our results indicated that agronomic management like optimum time of sowing, cultivar duration, and establishment methods should be followed for yield improvement in tropical lowlands where light intensity is limiting due to prevailing weather situations.

An overview of the recent trends on the waste valorization techniques for food wastes.

A critical and up-to-date review has been conducted on the latest individual valorization technologies aimed at the generation of value-added by-products from food wastes in the form of bio-fuels, bio-materials, value added components and bio-based adsorbents. The aim is to examine the associated advantages and drawbacks of each technique separately along with the assessment of process parameters affecting the efficiency of the generation of the bio-based products. Challenges faced during the processing of the wastes to each of the bio-products have been explained and future scopes stated. Among the many hurdles encountered in the successful and high yield generation of the bio-products is the complexity and variability in the composition of the food wastes along with the high inherent moisture content. Also, individual technologies have their own process configurations and operating parameters which may affect the yield and composition of the desired end product. All these require extensive study of the composition of the food wastes followed by their effective pre-treatments, judicial selection of the technological parameters and finally optimization of not only the process configurations but also in relation to the input food waste material. Attempt has also been made to address the hurdles faced during the implementation of such technologies on an industrial scale.

C-reactive protein as a prognostic marker of Plasmodiumfalciparum malaria severity.

BACKGROUND & OBJECTIVES: Plasmodiumfalciparum malaria causes wide variety of clinical symptoms ranging from a mild febrile illness to life-threatening complications. For prevention of the severity and early diagnosis, evaluation of potential biomarkers is much needed. C-reactive protein (CRP) is an acute phase protein and well-recognized marker of inflammation in the body. It is synthesized by liver in response to pro-inflammatory responses and has correlation with complications associated with malaria. The study was aimed to assess, if it could serve as a predictive marker for malaria disease severity. METHODS: In the present study, 74 P. falciparum patients and 22 healthy controls were enrolled. Turbidimetric immunoassay was used to measure the CRP in serum samples of all the study participants. Mann-Whitney U-test for continuous data and chi-square test for categorical data were used to compare all malaria cases vs. healthy control group and uncomplicated vs. severe malaria groups. Using receiver operating characteristic (ROC) analysis, best threshold value was determined for CRP in severe malaria patients. RESULTS: CRP level was significantly elevated in all malaria case groups (1.6 mg/dl IQ 1-2.6) as compared to healthy controls (0.10 mg/dl IQ 0.1-0.20), with p-value <0.0001. Further, CRP level was significantly higher in the severe malaria group (2 mg/dl IQ 1.8-3.9) as compared to the uncomplicated malaria group (1.4 mg/dl IQ 1-2.47) and healthy control group (0.10 mg/dl IQ 0.10-0.20), with p-value <0.05. INTERPRETATION & CONCLUSION: The present study findings suggest that CRP level can be used to differentiate severe malaria from uncomplicated malaria. Elevated CRP level could be helpful in early prediction of the disease severity in patients infected with P. falciparum and may play an important role in diagnosis of falciparum malaria where improper initial test and clinical manifestations like fever may be absent even with a high load of parasite.

Ecosystem services in different agro-climatic zones in eastern India: impact of land use and land cover change.

Land use and land cover (LULC) change have considerable influence on ecosystem services. Assessing change in ecosystem services due to LULC change at different spatial and temporal scales will help to identify suitable management practices for sustaining ecosystem productivity and maintaining the ecological balance. The objective of this study was to investigate variations in ecosystem services in response to LULC change over 27 years in four agro-climatic zones (ACZ) of eastern India using satellite imagery for the year 1989, 1996, 2005, 2011 (Landsat TM) and 2016 (Landsat 8 OLI). The satellite images were classified into six LULC classes, agriculture land, forest, waterbody, wasteland, built-up, and mining area. During the study period (1989 to 2016), forest cover reduced by 5.2%, 13.7%, and 3.6% in Sambalpur, Keonjhar, and Kandhamal districts of Odisha, respectively. In Balasore, agricultural land reduced by 17.2% due to its conversion to built-up land. The value of ecosystem services per unit area followed the order of waterbodies > agricultural land > forests. A different set of indicators, e.g., by explicitly including diversity, could change the rank between these land uses, so the temporal trends within a land use are more important than the absolute values. Total ecosystem services increased by US$ 1296.4 × 105 (50.74%), US$ 1100.7 × 105 (98.52%), US$ 1867 × 105 (61.64%), and US$ 1242.6 × 105 (46.13%) for Sambalpur, Balasore, Kandhamal, and Keonjhar, respectively.

Enhancement of toxic Cr (VI), Fe, and other heavy metals phytoremediation by the synergistic combination of native Bacillus cereus strain and Vetiveria zizanioides L.

Bioremediation of Cr (VI), Fe, and other heavy metals (HMs) through plant-microbes interaction is one of the efficient strategies due to its high efficiency, low cost, and ecofriendly nature. The aim of the study was to isolate, characterize, and assess the potential of rhizospheric bacteria to enhance growth and metal accumulation by the chromium hyperaccumulator Vetiveria zizanoides. The bacterial strain isolated from mine tailings was identified to be Bacillus cereus (T1B3) strain exhibited plant growth-promoting traits including, 1-aminocyclopropane-1-carboxylate deaminase, indole acetic acid, and siderophores production, nitrogen fixation, and P solubilization. Removal capacity (mg L-1) of T1B3 strain was 82% for Cr+6 (100), 92% for Fe (100), 67% for Mn(50), 36% for Zn (50), 31% for Cd (30), 25% for Cu (30), and 43% for Ni (50) during the active growth cycle in HM-amended, extract medium. Results indicate that inoculating the native V. zizanioides with T1B3 strain improves its phytoremediation efficiency of HMs. The mineralogical characteristics of chromite ore tailings and soil were also confirmed by X-ray diffraction, Fourier Transform Infrared, scanning electron microscope-energy dispersive spectroscopy analysis.

Larvicidal activity of Ricinus communis extract against mosquitoes.

BACKGROUND & OBJECTIVES: Vector control strategies play significant role in reducing the transmission of malaria, dengue and other vector-borne diseases. The control of vector population using synthetic insecticides has resulted in development of insecticide resistance and negative effects on humans and environment. The present investigation evaluated the larvicidal potential of methanol, dichloromethane and hexane extracts of leaves and seeds of Ricinus communis (castor) plant against the early IV instar larvae of the dengue vector, Aedes aegypti, and malaria vector, Anopheles culicifacies. METHODS: Plant extracts were screened for their efficacy against Ae. aegypti and An. culicifacies using WHO standard larval susceptibility test method. Dose response bioassay was performed to get lethal concentrations. Further, gas chromatography-mass spectroscopy (GC-MS) analysis was carried out to identify the bioactive chemical constituents of the extracts of R. communis. Toxicity of the extracts towards non-target organism, Poecilia reticulata was also evaluated. RESULTS: The leaf and seed extracts of R. communis showed significant mortality against the larvae of Ae. aegypti and An. culicifacies at concentrations of 31.25, 62.5, 125, 250, 500 ppm; and 2, 4, 8, 16, 32, 64 ppm, respectively. At 24 h of the exposure period, the larvicidal activities were highest for the methanol extract of seeds with LC50 15.52 and 9.37 ppm and LC90 45.24 and 31.1 ppm for Ae. aegypti and An. culicifacies, respectively. The methanol extract of seeds and leaves was found to be safe towards non-target organism, P. reticulata. The GC-MS profile showed that seed extracts were having higher concentration of stigmasterol (7.5%), ß-sitosterol (11.48%), methyl linoleate (2.5%), vitamin E (11.93%), and ricinoleic acid (34%) than the leaf extracts. INTERPRETATION & CONCLUSION: The seed extract of R. communis has better larvicidal activity than the leaf extract and can be used as an effective larvicide against mosquitoes. The non-toxicity of the extracts towards P. reticulata further suggests that these plant extracts could be used along with predatory fishes in integrated vector control approaches.

Impact of germline and somatic missense variations on drug binding sites.

Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and germline nsSNVs that disrupt these binding sites can provide valuable knowledge for personalized medicine treatment. A web portal is available where nsSNVs from individual patient can be checked by scanning against DrugVar to determine whether any of the SNVs affect the binding of any drug in the database.

Subchronic exposures to fungal bioaerosols promotes allergic pulmonary inflammation in naïve mice.

BACKGROUND: Epidemiological surveys indicate that occupants of mold contaminated environments are at increased risk of respiratory symptoms. The immunological mechanisms associated with these responses require further characterization. OBJECTIVE: The aim of this study was to characterize the immunotoxicological outcomes following repeated inhalation of dry Aspergillus fumigatus spores aerosolized at concentrations potentially encountered in contaminated indoor environments. METHODS: Aspergillus fumigatus spores were delivered to the lungs of naïve BALB/cJ mice housed in a multi-animal nose-only chamber twice a week for a period of 13 weeks. Mice were evaluated at 24 and 48 h post-exposure for histopathological changes in lung architecture, recruitment of specific immune cells to the airways, and serum antibody responses. RESULT: Germinating A. fumigatus spores were observed in lungs along with persistent fungal debris in the perivascular regions of the lungs. Repeated exposures promoted pleocellular infiltration with concomitant epithelial mucus hypersecretion, goblet cell metaplasia, subepithelial fibrosis and enhanced airway hyperreactivity. Cellular infiltration in airways was predominated by CD4(+) T cells expressing the pro-allergic cytokine IL-13. Furthermore, our studies show that antifungal T cell responses (IFN-γ(+) or IL-17A(+) ) co-expressed IL-13, revealing a novel mechanism for the dysregulated immune response to inhaled fungi. Total IgE production was augmented in animals repeatedly exposed to A. fumigatus. CONCLUSIONS & CLINICAL RELEVANCE: Repeated inhalation of fungal aerosols resulted in significant pulmonary pathology mediated by dynamic shifts in specific immune populations and their cytokines. These studies provide novel insights into the immunological mechanisms and targets that govern the health outcomes that result from repeated inhalation of fungal bioaerosols in contaminated environments.

Influence of Aspergillus fumigatus conidia viability on murine pulmonary microRNA and mRNA expression following subchronic inhalation exposure.

BACKGROUND: Personal exposure to fungal bioaerosols derived from contaminated building materials or agricultural commodities may induce or exacerbate a variety of adverse health effects. The genomic mechanisms that underlie pulmonary immune responses to fungal bioaerosols have remained unclear. OBJECTIVE: The impact of fungal viability on the pulmonary microRNA and messenger RNA profiles that regulate murine immune responses was evaluated following subchronic inhalation exposure to Aspergillus fumigatus conidia. METHODS: Three groups of naïve B6C3F1/N mice were exposed via nose-only inhalation to A. fumigatus viable conidia, heat-inactivated conidia (HIC), or HEPA-filtered air twice a week for 13 weeks. Total RNA was isolated from whole lung 24 and 48 h postfinal exposure and was further processed for gene expression and microRNA array analysis. The molecular network pathways between viable and HIC groups were evaluated. RESULTS: Comparison of data sets revealed increased Il4, Il13 and Il33 expression in mice exposed to viable vs. HIC. Of 415 microRNAs detected, approximately 50% were altered in mice exposed to viable vs. HIC 48 h postexposure. Significantly down-regulated (P ≤ 0.05) miR-29a-3p was predicted to regulate TGF-ß3 and Clec7a, genes involved in innate responses to viable A. fumigatus. Also significantly down-regulated (P ≤ 0.05), miR-23b-3p regulates genes involved in pulmonary IL-13 and IL-33 responses and SMAD2, downstream of TGF-ß signalling. Using Ingenuity Pathway Analysis, a novel interaction was identified between viable conidia and SMAD2/3. CONCLUSIONS AND CLINICAL RELEVANCE: Examination of the pulmonary genetic profiles revealed differentially expressed genes and microRNAs following subchronic inhalation exposure to A. fumigatus. MicroRNAs regulating genes involved in the pulmonary immune responses were those with the greatest fold change. Specifically, germinating A. fumigatus conidia were associated with Clec7a and were predicted to interact with Il13 and Il33. Furthermore, altered microRNAs may serve as potential biomarkers to evaluate fungal exposure.