Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this ...process by repressing E-cadherin and enhancing vimentin and N-cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic ductal adenocarcinomas (PDA). In this study, we show that over expression of MUC1 in pancreatic cancer cells triggers the molecular process of EMT, which translates to increased invasiveness and metastasis. EMT was significantly reduced when MUC1 was genetically deleted in a mouse model of PDA or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to phenylalanine (mutated MUC1 CT). Using proteomics, RT-PCR and western blotting, we revealed a significant increase in vimentin, Slug and Snail expression with repression of E-Cadherin in MUC1-expressing cells compared with cells expressing the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed to co-immunoprecipitate with β-catenin and translocate to the nucleus, thereby blocking transcription of the genes associated with EMT and metastasis. Thus, functional tyrosines are critical in stimulating the interactions between MUC1 and β-catenin and their nuclear translocation to initiate the process of EMT. This study signifies the oncogenic role of MUC1 CT and is the first to identify a direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may have implications in future design of MUC1-targeted therapies for pancreatic cancer.
IgG is the predominant immunoglobulin in cervicovaginal mucus (CVM), yet how immunoglobulin G (IgG) in mucus can protect against infections is not fully understood. IgG diffuses rapidly through ...cervical mucus, slowed only slightly by transient adhesive interactions with mucins. We hypothesize that this almost unhindered diffusion allows IgG to accumulate rapidly on pathogen surfaces, and the resulting IgG array forms multiple weak adhesive crosslinks to mucus gel that effectively trap (immobilize) pathogens, preventing them from initiating infections. Here, we report that herpes simplex virus serotype 1 (HSV-1) readily penetrated fresh, pH-neutralized ex vivo samples of CVM with low or no detectable levels of anti-HSV-1 IgG but was trapped in samples with even modest levels of anti-HSV-1 IgG. In samples with little or no endogenous anti-HSV-1 IgG, addition of exogenous anti-HSV-1 IgG, affinity-purified from intravenous immunoglobulin, trapped virions at concentrations below those needed for neutralization and with similar potency as endogenous IgG. Deglycosylating purified anti-HSV-1 IgG, or removing its Fc component, markedly reduced trapping potency. Finally, a non-neutralizing IgG against HSV-gG significantly protected mice against vaginal infection, and removing vaginal mucus by gentle lavage abolished protection. These observations suggest that IgG-Fc has a glycan-dependent "muco-trapping" effector function that may provide exceptionally potent protection at mucosal surfaces.
The colon epithelium is covered by two layers of mucus built around the MUC2 mucin. An inner dense and attached mucus layer does not allow bacteria to penetrate, thus keeping the epithelial cell ...surface free from bacteria. An outer loose mucus layer is the habitat for the commensal bacterial microbiota. The inner mucus layer is renewed from the epithelial side and gets converted into the outer layer due to proteolytic cleavages by host proteases. We have now analysed if potential probiotic bacteria, namely Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus bulgaricus and Bifidobacterium lactis, can secrete protease that cleaves the MUC2 mucin. We found that none of the potential probiotic bacteria Lactobacillus and Bifidobacterium could cleave the MUC2 core protein in the form of recombinant MUC2 N and C-termini although they secreted active proteases. This was in contrast to crude mixtures of oral and faecal bacteria that cleaved the MUC2 mucin. This observation further supports the view that these potential probiotic bacteria are of no harm to the host, as these bacteria cannot disrupt the mucin organised mucus as long as they are covered by glycans.
Background. Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff mm score is not reproducible and may miss important ME features. The study aimed to ...improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss. Methods. We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff mm score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %ME mm (%glomeruli with ME in ≥2 lobules, like Banff mm ); (2) %ME any (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss. Results. From 1- to 5-y biopsies, the mean Banff mm score increased from 0.18 to 0.34, whereas %ME mm increased from 2.5% to 13.3%. Banff mm score had modest correlations with morphometric ME measures. Moderate-severe %ME mm was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff mm scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff mm score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %ME any had the highest c-statistic (0.872). Conclusions. Banff mm score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.
In order to assess the geochemical mechanism liable for fluoride contamination in groundwater and its health effects on the people of the Shanmuganadhi River basin, Tamil Nadu, India, 61 groundwater ...samples were collected during post- and pre-monsoon seasons from the wells used for drinking purposes. Collected samples were analysed for various physico-chemical parameters. The parameters estimated in the present study are hydrogen ion concentration (pH), total dissolved solids, electrical conductivity, calcium (Ca
2+
), magnesium (Mg
2+
), sodium (Na
+
), potassium (K
+
), bicarbonate (HCO
3
−
), chloride (Cl
−
), sulphate (SO
4
2−
), nitrate (NO
3
−
), phosphate (PO
4
3−
) and fluoride (F
−
). The fluoride ion concentration in the groundwater samples of this region varied from 0.01 to 2.50 mg/l and 0.01 to 3.30 mg/l during post- and pre-monsoon seasons, respectively. Out of 61 groundwater samples, 14 samples of post-monsoon season and 16 samples of pre-monsoon season represented high, very high and extremely high classes of fluoride, which cause dental fluorosis in this region. The fluoride-bearing minerals in the granitic and gneissic rocks such as apatite, hornblende, muscovite, biotite and amphiboles are the major sources for fluoride contamination in this area. In addition to the geogenic sources, applications of synthetic fertilizers in the agricultural fields also contribute significant amount of fluoride ions to groundwater. The spatial distribution of fluoride in different geological formations clearly indicate that the wells located in charnockite terrain were possessing very low fluoride concentration when compare with the wells located in the hornblende–biotite gneiss formation. Therefore, dental fluorosis risks are mostly associated with rock types in this region. People living over the basement rock comprising of hornblende–biotite gneiss are prone for fluorosis. Fluoride exhibited good positive correlation with bicarbonate in groundwater. As fluoridated endemic regions normally acquire lot of bicarbonate in groundwater samples, Shanmuganadhi basin falls under fluoride endemic category. The present study identified 26 villages in Shanmuganadhi basin as probable fluorosis risk areas where attention should be given to treat the fluoride-rich groundwater before drinking water supply. The groundwater level fluctuation study also designates that rise in water level reduces the concentration of fluoride due to dilution mechanism. Therefore, recharge of groundwater by artificial methods will definitely improve the present scenario.
The effect of particle hardness on the erosion of stainless steel has been studied with fine particles at low impacting velocities with two experimental apparatuses, submerged configuration with ...slurry mix and mist flow test with solid particles entrained in the droplets. Particle concentration was 1% by mass and the tests have been run for 72h. The testing particles include iron powder, calcite, barite, hematite, magnetite, silica flour, alumina and silicon carbide which are smaller than 40µm with Vickers׳s hardness of 65–3000kgfmm−2. A Particle Image Velocimeter (PIV) is used to measure droplet size and velocity for air/water tests, and Computational Fluid Dynamics (CFD) with particle tracking scheme is implemented to estimate the particle impact velocities for both cases. The measured erosion ratio was consistent for most of the particles in the two testing configurations. It was observed that erosion ratio increases with increasing particle hardness when target material is harder than the particle and does not change considerably after a point where the particle is hard enough to keep its integrity during impact. A correlation has been proposed to correlate erosion ratio (mass of material loss/mass of particles) to the particle hardness by considering the effect of particle impact velocity and angularity of the particles.
•The effect of erodent particle properties on the erosion of SS-316 is studied.•The tests have been conducted in two configurations, submerged and mist flow.•Erosion has been correlated to particle hardness.•The effect of particle angularity and impact velocity is considered.
The artificial recharge is an alternative technique to augment surface water and groundwater and for providing continuous supply of water to the demand regions. The scope of contemporary study helps ...in evaluation of groundwater potential zones and to find proper zones and sites for groundwater recharge using geospatial and multi-criteria decision analysis (MCDA) techniques. In this study, the pragmatic methodology was proposed for the implementation of water harvesting structures. The satellite and conventional datasets with field inferences were systematically processed to obtain various thematic information of the study area. The analytical hierarchical process (AHP) in geographical information system (GIS) was utilized to assign the geometric mean and the normalized weight for the individual features. Further, groundwater potential zones were identified, and they were categorized into four types viz. very high (523.58 km
2
), high (798.22 km
2
), moderate (646.04 km
2
) and low (456.66 km
2
). Nearly, 54.52% of the study area falls in the ‘very high’ to ‘high’ potential categories. The GIS-based Boolean logical method was also executed to identify suitable areas for creating recharge structures such as check dams (127.47 km
2
), percolation ponds (115.23 km
2
), flood and furrows (63.01 km
2
) and ditch and furrows (1046.31 km
2
). Based on the above results, 36 water harvesting structures were promoted to augment the groundwater resources of the basin. The highest priority was given to check dams (19 Nos), followed by percolation ponds (7 Nos), flood and furrows (5 Nos) and ditch and furrows (5 Nos). The suggested structures would improve the groundwater availability for agriculture and domestic purposes in the study area. Further, the outcomes could deliver a scientific procedure to the decision makers and water scientists for effective water resources development and management planning. Overall, the integrated remote sensing, GIS and MCDA methods are an efficient and useful tool for planning and improving groundwater recharge in the basin scale.
Groundwater resources are used in various parts of the world to meet out drinking water supply, irrigational practices and industrial applications. These valuable resources are naturally replenished ...by rainfall infiltration. Due to population growth and industrialization, groundwater resources are often overexploited in different parts of the world particularly in the hard rock areas. It leads to rapid declination in the groundwater level. Therefore, groundwater fluctuation with respect to space and time governs attention throughout the world for the purpose of sustainable management of water resources. In the present study, long-term trend detection and spatiotemporal variation of groundwater levels were analyzed using Geographical Information System (GIS) and performing statistical tests for the Lower Bhavani River basin, Tamil Nadu, India. For this purpose, 32 years long-term groundwater-level data (1984–2015) of 57 observation wells spread over the study area were collected from the government departments. Seasonal variation of groundwater levels was plotted spatially for pre-monsoon (March to May), post-monsoon (January and February), southwest (SW) monsoon (June to September) and northeast (NE) monsoon (October to December) seasons using GIS. The trend variation of groundwater levels was predicted by performing statistical tests such as Mann–Kendall test and Sen’s slope estimator. The present study indicates that the average annual groundwater level has lowered beyond 15 m (below ground level) during all the monsoon seasons in the year 2003 and 2004, which highlights less rainfall infiltration and overexploitation of groundwater. This leads the hard rock aquifer into stress. The study also shows that the groundwater fluctuation is very high in the southeastern and northeastern parts of the basin, and it is moderate in the northern and northwestern parts of the basin. However, the fluctuation is comparatively less in the central part of the basin because of replenishment of groundwater by the Bhavani River. The trend analysis highlights that declining water table is mostly found during SW monsoon season (summer season), which is observed more than 50% area of the basin. The places such as Emmampoondi, Kumbapanai, Kandisalai, Alukuli, Perikoduveri, P.Mettupalayam, Pudupalayam, Sathyamangalam, Nallagoundanpudur, Kullampalayam and Baguthampalayam are mostly affected by the declining trend in the groundwater level. Therefore, this study recommends for the implementation of large-scale rainwater harvesting system in the Lower Bhavani River basin to augment groundwater resources.
Water is one of the important sources for the survival of living species on the earth. As earth having only a small amount of water resources for drinking purpose people in rural and urban areas are ...getting affected by consuming contaminated water that leads to water-borne diseases. Even ground water has to be properly treated before its use for internal consumption. Salt water contains dissolved and undissolved contents and hence it is not suitable for domestic purpose (cleaning, washing, bathing, etc.). This paper completely deals with the detailed review of a solar still integrated to solar collectors for augmenting the yield of fresh water. However, these methods appear to be uneconomical to the middle and low-income families. The yield, economic aspects and payback period of different solar still are reviewed, and a possible conclusion with the integration of low-cost solar water heater and nanofluids in solar water heater are arrived.
Rainfall and surface runoff are the two most important components, which control the groundwater recharge of the basin. The long-term groundwater recharge of an aquifer gets affected by the ...population growth, irregular agriculture activities and industrialization. Hence, estimation of rainfall-surface runoff is very much essential for proper groundwater management practices. In the present study, Soil Conservation Service Curve Number (SCS-CN) model was employed in combination with geospatial techniques to estimate rainfall-surface runoff for the Lower Bhavani River basin in South India. To develop the SCS-CN model, rainfall data were obtained for 33 years (1983–2015) from 22 rain gauge stations spread over the basin. IRS LISS-IV satellite data of 5.8 m spatial resolution were used to analyze the land use/land cover (LU/LC) behavior. Based on the soil properties, four Hydrological Soil Groups (HSG) were identified in the basin which is most significant for surface runoff estimation. Curve Number (CN) values were obtained for various Antecedent Moisture Conditions (AMC) such as dry condition (AMC I), average condition (AMC II) and wet condition (AMC III). Spatial distribution of CN values was plotted using Geographical Information System (GIS) for the entire Lower Bhavani Basin to assess the surface runoff potential. The results indicate that the annual rainfall varies from 267 mm (2002) to 1528.6 mm (2005), and the annual surface runoff varies from 102.04 mm (1985) to 463.02 mm (2010). The SCS-CN model outputs predict that the average surface runoff of the basin is 211.99 mm, and the average surface runoff volume is 81,995,380 m
3
. The study also indicates that nearly 53% of the basin area is dominated by high to very high surface runoff potential. Finally, the output of surface runoff potential was validated with the Average Groundwater Level Fluctuation (AGLF) observed in 57 wells spread over the entire basin. The basin AGLF ranges from 2.32 to 21.72 m. The surface runoff potential categories are satisfactorily matching with the AGLF categories. Moderate surface runoff as well as moderate AGLF zones mostly occupy the central portion of the basin, which possess good groundwater potential. However, the high surface runoff zones in the basin lead more surface water flow into the river channels, which reduce the infiltration rate and decline the water table. This problem can be solved by constructing suitable artificial groundwater recharge structures across the river channels in the high surface runoff potential areas.
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