New cyclophilin D inhibitor rescues mitochondrial and cognitive function in Alzheimer's disease.

Mitochondrial dysfunction is an early pathological feature of Alzheimer disease and plays a crucial role in the development and progression of Alzheimer's disease. Strategies to rescue mitochondrial function and cognition remain to be explored. Cyclophilin D (CypD), the peptidylprolyl isomerase F (PPIase), is a key component in opening the mitochondrial membrane permeability transition pore, leading to mitochondrial dysfunction and cell death. Blocking membrane permeability transition pore opening by inhibiting CypD activity is a promising therapeutic approach for Alzheimer's disease. However, there is currently no effective CypD inhibitor for Alzheimer's disease, with previous candidates demonstrating high toxicity, poor ability to cross the blood-brain barrier, compromised biocompatibility and low selectivity. Here, we report a new class of non-toxic and biocompatible CypD inhibitor, ebselen, using a conventional PPIase assay to screen a library of ∼2000 FDA-approved drugs with crystallographic analysis of the CypD-ebselen crystal structure (PDB code: 8EJX). More importantly, we assessed the effects of genetic and pharmacological blockade of CypD on Alzheimer's disease mitochondrial and glycolytic bioenergetics in Alzheimer's disease-derived mitochondrial cybrid cells, an ex vivo human sporadic Alzheimer's disease mitochondrial model, and on synaptic function, inflammatory response and learning and memory in Alzheimer's disease mouse models. Inhibition of CypD by ebselen protects against sporadic Alzheimer's disease- and amyloid-ß-induced mitochondrial and glycolytic perturbation, synaptic and cognitive dysfunction, together with suppressing neuroinflammation in the brain of Alzheimer's disease mouse models, which is linked to CypD-related membrane permeability transition pore formation. Thus, CypD inhibitors have the potential to slow the progression of neurodegenerative diseases, including Alzheimer's disease, by boosting mitochondrial bioenergetics and improving synaptic and cognitive function.

Exploratory modelling of the impacts of sea-level rise on the Sundarbans mangrove forest, West Bengal, India.

In this paper we conduct exploratory simulations of the possible evolution of the Indian Sundarbans mangroves to 2100 under a range of future sea-level rise (SLR) scenarios, considering the effects of both inundation and shoreline erosion. The Sea Level Affecting Marshes Model (SLAMM) is used to simulate habitat transitions due to inundation and these outputs are combined with an empirical model of SLR-driven shoreline erosion. A set of plausible climate-induced SLR scenarios are considered, together with delta subsidence and constrained vertical sediment accretion. Significant mangrove decline is found in all cases: the greater the rise in sea level the greater the losses. By the end of the century, the Indian Sundarbans mangroves could lose between 42 % and 80 % of their current area if current management is continued. Managed realignment could offset these losses but at the expense of productive land and the migration of the human population.

Mapping of tide-dominated Hooghly estuary water quality parameters using Sentinel-3 OLCI time-series data.

The study explores the spatio-temporal variation of water quality parameters in the Hooghly estuary, which is considered an ecologically-stressed shallow estuary and a major distributary for the Ganges River. The estimated parameters are chlorophyll-a, total suspended matter (TSM), and chromophoric dissolved organic matter (CDOM). The Sentinel-3 OLCI remote sensing imageries were analyzed for the duration of October 2018 to February 2019. We observed that the water quality of the Hooghly estuaries is comparatively low-oxygenated, mesotrophic, and phosphate-limited. Ongoing channel dredging for maintaining shipping channel depth keeps the TSM in the estuary at an elevated level, with the highest amount of TSM observed during March of 2019 (41.59g m-3) at station A, upstream point. Since the pre-monsoon season, TSM data shows a decreasing trend towards the mouth of the estuary. Chl-a concentration is higher during pre-monsoon than monsoon and post-monsoon periods, with the highest value observed in April at 1.09 mg m-3 in station D during the pre-monsoon period. The CDOM concentration was high in the middle section (January-February) and gradually decreased towards the estuary's head and mouth. The highest CDOM was found in February at locations C and D during the pre-monsoon period. Every station shows a significant correlation among CDOM, TSM, and Chl-a measured parameters. Based on our satellite data analysis, it is recommended that SNAP C2RCC be regionally used for TSM, Chl-a, and CDOM for water quality product retrieval and in various algorithms for the Hooghly estuary monitoring.

Multifunctional Architectures of Cyclic Dipeptide Copolymers and Composites, and Modulation of Multifaceted Amyloid-ß Toxicity.

Alzheimer's disease (AD) is a major neurodegenerative disorder primarily characterized by the ß-amyloid (Aß42) misfolding and aggregation-associated multifaceted amyloid toxicity encompassing oxidative stress, neuronal death, and severe cognitive impairment. Modulation of Aß42 aggregation via various structurally anisotropic macromolecular systems is considered effective in protecting neuronal cells. In this regard, we have developed a cyclic dipeptide (CDP)-based copolymer (CP) and explored its material and biomedical properties. Owing to the structural versatility, CDP-CP forms solvent-dependent anisotropic architectures ranging from dense fibers and mesosheets to vesicles, which are shown to interact with dyes and nanoparticles and mimic synthetic protocells, providing a conceptually new approach to achieve advanced functional materials with the hierarchical organization. CP upon interaction with gold nanoparticles (GNP) and polyoxometalate (POM) generated faceted architectures (CP-GNP) and the nanocomposite (CP-POM), respectively. CP-GNP and CP-POM have shown remarkable ability to inhibit Aß42 aggregation, dissolve the preformed aggregates, and scavenge reactive oxygen species (ROS) to ameliorate multifaceted amyloid toxicity. In cellulo studies show that CP-GNP and CP-POM protect neuronal cells from Aß42-induced toxicity and reduce lipopolysaccharide (LPS)-activated neuroinflammation at sub-micromolar concentration. To our knowledge, this is the first report on the hierarchical organization of CDP-CP into 1D-to-2D architectures and their organic-inorganic hybrid nanocomposites to combat the multifaceted amyloid toxicity.

Antioxidant Silk Fibroin Composite Hydrogel for Rapid Healing of Diabetic Wound.

Wound healing is a complex process requiring multiple biological pathways and chemical responses to be activated and synchronized to recover tissue integrity. In normal physiological circumstances, the epidermal barrier restoration process through new tissue formation is highly efficient. However, increased production of reactive oxygen species (ROS), attack of pathogenic microorganisms, and high glucose level delay the normal healing process in diabetic patients. The successful treatment of diabetic wounds requires efficient strategies to control oxidative stress, promoting angiogenesis, re-epithelialization, and collagen deposition. In this study, a composite hydrogel for rapid wound healing in diabetic condition is developed by the amalgamation of hypolipidemic property of silk fibroin (SF), antioxidant property of melanin, and therapeutic effect of berberine. Studies have revealed that cross-linked mesoporous morphology of hydrogel matrix facilitates slow release of berberine to impart long-term therapeutic effects at wound site. The composite hydrogel formulation is biocompatible, stimulates effective migration of fibroblast cells, and control oxidative stress under in vitro conditions. The hydrogel served as scaffold for tissue re-epithelialization and promotes wound repair in diabetic type I Wistar rat model. This study demonstrates the ability of berberine- loaded SF-melanin composite hydrogel as a potential dressing formulation for wound healing in diabetic conditions.

Combating amyloid-induced cellular toxicity and stiffness by designer peptidomimetics.

Amyloid beta (Aß) aggregation species-associated cellular stress instigates cytotoxicity and adverse cellular stiffness in neuronal cells. The study and modulation of these adverse effects demand immediate attention to tackle Alzheimer's disease (AD). We present a de novo design, synthesis and evaluation of Aß14-23 peptidomimetics with cyclic dipeptide (CDP) units at defined positions. Our study identified AkdNMC with CDP units at the middle, N- and C-termini as a potent candidate to understand and ameliorate Aß aggregation-induced cellular toxicity and adverse stiffness.

Earth observation and geospatial data can predict the relative distribution of village level poverty in the Sundarban Biosphere Reserve, India.

There is increasing interest in leveraging Earth Observation (EO) and geospatial data to predict and map aspects of socioeconomic conditions to support survey and census activities. This is particularly relevant for the frequent monitoring required to assess progress towards the UNs' Sustainable Development Goals (SDGs). The Sundarban Biosphere Reserve (SBR) is a region of international ecological importance, containing the Indian portion of the world's largest mangrove forest. The region is densely populated and home to over 4.4 million people, many living in chronic poverty with a strong dependence on nature-based rural livelihoods. Such livelihoods are vulnerable to frequent natural hazards including cyclone landfall and storm surges. In this study we examine associations between environmental variables derived from EO and geospatial data with a village level multidimensional poverty metric using random forest machine learning, to provide evidence in support of policy formulation in the field of poverty reduction. We find that environmental variables can predict up to 78% of the relative distribution of the poorest villages within the SBR. Exposure to cyclone hazard was the most important variable for prediction of poverty. The poorest villages were associated with relatively small areas of rural settlement (<∼30%), large areas of agricultural land (>∼50%) and moderate to high cyclone hazard. The poorest villages were also associated with less productive agricultural land than the wealthiest. Analysis suggests villages with access to more diverse livelihood options, and a smaller dependence on agriculture may be more resilient to cyclone hazard. This study contributes to the understanding of poverty-environment dynamics within Low-and middle-income countries and the associations found can inform policy linked to socio-environmental scenarios within the SBR and potentially support monitoring of work towards SDG1 (No Poverty) across the region.

Economic incentives drive the conversion of agriculture to aquaculture in the Indian Sundarbans: Livelihood and environmental implications of different aquaculture types.

Expansion of aquaculture in the Sundarbans Biosphere Reserve (SBR) is irreversibly replacing agricultural land and the drivers of this change are disputed. Based on in-depth interviews with 67 aquaculture farmers, this paper characterizes major aquaculture types in the SBR, their impacts, and identifies drivers of conversion from agricultural land. Aquaculture types included traditional, improved-traditional, modified-extensive, and semi-intensive systems. Extensive capture of wild shrimp larvae is environmentally harmful but constitutes an important livelihood. Semi-intensive aquaculture of exotic shrimp (Litopenaeus vannamei) has much higher unit-area profitability than other types but involves greater financial risk. Profitability is the main driver for the transition from agriculture, but environmental factors such as lowered crop yields and cyclone impacts also contributed. Many conversions from agriculture to aquaculture are illegal according to the stakeholders. Existing legislation, if enforced, could halt the loss of agriculture, while the promotion of improved-traditional aquaculture could reduce the demand for wild seed.

Stiffness prediction on elastography images and neuro-fuzzy based segmentation for thyroid cancer detection.

The elastography method detects metastatic changes by measuring the stiffness of tissues. Estimation of elasticities from elastography images facilitates more precise identification of the metastatic region and detection of the same. In this study, an automated segmentation algorithm is proposed that calculates pixel-wise elasticity values to detect thyroid cancer from elastography images. This intensity to elasticity conversion is achieved by constructing a fuzzy inference system using an adaptive neuro-fuzzy inference system supported by two meta-heuristic algorithms: genetic algorithm and particle swarm optimization. Pixels of the input color images (red, green, and blue) are replaced by equivalent elasticity values (in kilo Pascal) and are stored in a two-dimensional array to form an "elasticity matrix." The elasticity matrix is then segmented into three regions, namely, suspicious, near-suspicious, and non-suspicious, based on the elasticity measures, where the threshold limits are calculated using the fuzzy entropy maximization method optimized by the differential evolution algorithm. Segmentation performances are evaluated by Kappa and the dice similarity co-efficient, and average values achieved are 0.94±0.11 and 0.93±0.12, respectively. Sensitivity and specificity values achieved by the proposed method are 86.35±0.34% and 97.67±0.40%, respectively, showing an overall accuracy of 93.50±0.42%. Results justify the importance of pixel stiffness for segmentation of thyroid nodules in elastography images.

Identification of Multicolor Fluorescent Probes for Heterogeneous Aß Deposits in Alzheimer's Disease.

Accumulation of amyloid-beta (Aß) into amyloid plaques and hyperphosphorylated tau into neurofibrillary tangles (NFTs) are pathological hallmarks of Alzheimer's disease (AD). There is a significant intra- and inter-individual variability in the morphology and conformation of Aß aggregates, which may account in part for the extensive clinical and pathophysiological heterogeneity observed in AD. In this study, we sought to identify an array of fluorescent dyes to specifically probe Aß aggregates, in an effort to address their diversity. We screened a small library of fluorescent probes and identified three benzothiazole-coumarin derivatives that stained both vascular and parenchymal Aß deposits in AD brain sections. The set of these three dyes allowed the visualization of Aß deposits in three different colors (blue, green and far-red). Importantly, two of these dyes specifically stained Aß deposits with no apparent staining of hyperphosphorylated tau or α-synuclein deposits. Furthermore, this set of dyes demonstrated differential interactions with distinct types of Aß deposits present in the same subject. Aß aggregate-specific dyes identified in this study have the potential to be further developed into Aß imaging probes for the diagnosis of AD. In addition, the far-red dye we identified in this study may serve as an imaging probe for small animal imaging of Aß pathology. Finally, these dyes in combination may help us advance our understanding of the relation between the various Aß deposits and the clinical diversity observed in AD.

Effects of COVID-19 pandemic on the air quality of three megacities in India.

COVID-19 pandemic compelled many countries in the world to go for a nationwide lockdown to prevent the spread of the coronavirus. India started the lockdown on 24 March 2020. We analyzed the air quality of three megacities of India, namely Mumbai, Delhi, and Kolkata, during the lockdown phase and compared it with the pre-lockdown and post-lockdown scenarios. We considered seven major air pollutants: PM2.5, PM10, NO2, NH3, SO2, CO, and O3. We analyzed the data acquired from 56 automatic air-monitoring stations (AAMS) under the Central Pollution Control Board (CPCB) spread across the megacities. The air pollution level in the eastern part of Mumbai and the western part of Delhi and Kolkata usually remains high. Delhi was the worst polluted megacity, followed by Kolkata and Mumbai. The stop of vehicular movements and industrial lockdown across the nation has substantial effects on the environment, especially in the atmosphere near the Earth's surface. Our analysis showed significant improvements in air quality during the period of lockdown (25 March to 14 April 2020) compared to the pre-lockdown phase (3 March to 23 March 2020) and the same time window of the previous year (25 March to 14 April 2019). The post-lockdown (15 April to 5 May) phase exhibited mixed results. We mapped the spatial pattern of these pollutants and the air quality index (AQI). According to CPCB, PM2.5, PM10, and CO are the major air pollutants in India that reduced by 47%, 41%, and 27% in Mumbai; 52%, 39%, and 13% in Delhi; and 49%, 37%, and 21% in Kolkata, respectively, in the lockdown phase. PM2.5, PM10, and NO2 exhibited significant correlations across the three megacities. This study shows that occasional short-term lockdowns can effectively refresh the air in these megacities.

Polyampholyte-Based Synthetic Chaperone Modulate Amyloid Aggregation and Lithium Delivery.

Protein misfolding and aggregation is the pathological hallmark of Alzheimer's disease (AD). The etiopathogenesis of AD involves the accumulation of amyloid-ß (Aß) plaques in the brain, which disrupt the neuronal network and communication, causing neuronal death and severe cognitive impairment. Modulation of Aß aggregation by exogenous therapeutic agents is considered an effective strategy to treat AD. Frequent failure of drug candidates in various phases of clinical trials reiterates the need for alternative therapeutic strategies for AD treatment. Polyampholytes with cationic and anionic segments are considered as artificial protein mimics capable of modulating the protein misfolding and aggregation. We report a diblock copolymer of tryptophan-functionalized methacrylic acid (PTMA) polyampholyte synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization. Investigation revealed that PTMA acts as a synthetic chaperone to protect the native structure of the lysozyme under heat-induced aggregation conditions. PTMA effectively modulates Aß aggregation and rescues neuronal cells. Lithium has been shown to exhibit therapeutic efficacy in chronic neurological diseases including AD. PTMA sequesters and releases lithium ions in response to neuropathological pH stimuli, making it a promising candidate for lithium transport and delivery. The detailed studies demonstrate PTMA as aggregation modulator and lithium carrier with implications for combinational therapy to treat AD.

CO2 effluxes from an urban tidal river flowing through two of the most populated and polluted cities of India.

Urbanized rivers flowing through polluted megacities receive substantial amount of carbon from domestic sewage and industrial effluents which can significantly alter the air-water CO2 flux rates. In this regard, we quantified the partial pressure of CO2 in the surface water (pCO2(water)), air-water CO2 fluxes, and associated biogeochemical parameters in the Hooghly River, India, flowing through two of the most polluted cities of the country, Kolkata and Howrah, over a complete annual cycle during spring tidal phase (SP) and neap tidal phase (NP). This urbanized part of Hooghly River was always supersaturated with CO2 having an annual mean pCO2(water) and air-water CO2 flux of ~ 3800 µatm and ~ 49 mol C m-2 year-1, respectively. Significant seasonal variability was observed for both pCO2(water) and air-water CO2 flux (pre-monsoon, 3038 ± 539 µatm and 5049 ± 964 µmol m-2 h-1; monsoon, 4609 ± 711 µatm and 7918 ± 1400 µmol m-2 h-1; post-monsoon, 2558 ± 258 µatm and 4048 ± 759 µmol m-2 h-1, respectively). Monthly mean pH and total alkalinity varied from 7.482 to 8.099 and from 2437 to 4136 µmol kg-1, respectively, over the annual cycle. pCO2(water) showed significant positive correlation with turbidity and negative correlation with electrical conductivity and gross primary productivity (GPP). High water discharge could have facilitated high turbidity, especially during the monsoon season, which led to depletion in GPP and enhancement in pCO2(water) which in turn led to very high CO2 effluxes. The CO2 efflux rate in this urbanized riverine stretch was substantially higher than that observed in previous studies carried out in the less urbanized estuarine stretch of Hooghly. This indicates that the presence of highly urbanized and polluted metropolis potentially enhanced the pCO2(water) and CO2 effluxes of this river. Similar observations were made recently in some Asian and Australian urban rivers.

Antioxidant Berberine-Derivative Inhibits Multifaceted Amyloid Toxicity.

Multiple lines of evidence indicate that amyloid beta (Aß) peptide is responsible for the pathological devastation caused in Alzheimer's disease (AD). Aß aggregation species predominantly contribute to multifaceted toxicity observed in neuronal cells including generation of reactive oxygen species (ROS), mitochondrial dysfunction, interfering with synaptic signaling, and activation of premature apoptosis. Herein, we report a natural product berberine-derived (Ber-D) multifunctional inhibitor to ameliorate in cellulo multifaceted toxicity of AD. The structural attributes of polyphenolic Ber-D have contributed to its efficient Cu chelation and arresting the redox cycle to prevent the generation of ROS and rescue biomacromolecules from oxidative damage. Ber-D inhibits metal-dependent and -independent Aß aggregation, which is supported by in silico studies. Ber-D treatment averts mitochondrial dysfunction and corresponding neuronal toxicity contributing to premature apoptosis. These key multifunctional attributes make Ber-D a potential therapeutic candidate to ameliorate multifaceted Aß toxicity in AD.

Summer methane emissions from sewage water-fed tropical shallow aquaculture ponds characterized by different water depths.

Aquaculture practices are steadily increasing to meet the fish demand, especially in tropical countries like India. However, efforts to characterize the contribution of these aquaculture ponds towards greenhouse gas emission like CH4 are still very few. CH4 concentration in water [pCH4(water)] and air-water CH4 fluxes were estimated (during the summer months) in two sewage-fed ponds having different depths situated in the East Kolkata Wetlands, India (a Ramsar site). pCH4(water) in both of these ponds showed significant positive correlation with water temperature (R2 = 0.68 and 0.71, p < 0.05). Daily mean chlorophyll-a, turbidity, biochemical oxygen demand (BOD) and gross primary productivity (GPP) also showed positive correlation with pCH4(water). This indicated that higher primary production and presence of turbid materials acted as substrates for methanogenesis, which favoured air-water CH4 effluxes towards atmosphere. Mean air-water CH4 fluxes in the ponds having depth of 1.1 m and 0.6 m were observed to be 24.79 ± 12.02 mg m-2 h-1 and 6.05 ± 3.14 mg m-2 h-1 respectively. Higher depth facilitated net heterotrophic conditions, which led to lower dissolved oxygen levels, which, in turn, led to lower rate of CH4 oxidation. Moreover, under reduced photosynthetically active radiation (in the pond having greater depth), the pH values were comparatively lower (~7.7), which further facilitated a favourable condition for the methanogens to grow. On the whole, it was inferred that apart from pre-established physicochemical factors, depth was also found to play a decisive role in regulating the air-water CH4 fluxes from these aquaculture ponds. In future, continuous sampling should be carried out (by chamber method) to take into account the ebullition CH4 fluxes, and more number of ponds should be sampled throughout a complete annual cycle to have a more holistic understanding about this cluster of sewage-fed aquaculture ponds.

Injectable Silk Fibroin-Based Hydrogel for Sustained Insulin Delivery in Diabetic Rats.

Diabetes is a chronic disease affecting over 400 million people worldwide. Inadequate production of insulin due to loss of beta cells or insulin resistance within the body imbalances the glucose homeostasis, resulting in an abrupt increase of blood glucose level. The conventional and last resort of treatment involves repeated subcutaneous insulin injections to maintain the physiological glucose homeostasis. However, continuous and multiple subcutaneous injections are associated with poor patient compliance and local amyloidosis of insulin, which can be overcome with controlled and sustained insulin delivery. In this context, we have designed and formulated an injectable silk fibroin hydrogel (iSFH) to realize sustained insulin delivery over a prolonged period under diabetic conditions. The specific composition of glycol additives (ethylene glycol and triethylene glycol) allowed the silk fibroin protein to form an injectable hydrogel within 50 min. The detailed characterization of iSFH by a field-emission scanning electron microscope displayed the desired mesoporous structures, which are appropriate for drug (insulin) encapsulation in its active form. Interestingly, the subcutaneous injection of iSFH-encapsulated insulin (insulin-iSFH) in diabetic T1DM Wistar rats showed controlled release of insulin and restored physiological glucose homeostasis up to 4 days. The biocompatible and biodegradable nature of iSFH makes it a potential drug delivery system for active storage, and controlled and sustained delivery of insulin in diabetic conditions to maintain the physiological glucose level.

Unambiguous Detection of Elevated Levels of Hypochlorous Acid in Double Transgenic AD Mouse Brain.

Alzheimer's disease (AD) is one of the most prevalent forms of dementia. The current diagnosis methods based on the behavior and cognitive decline or imaging of core biomarkers, namely, amyloid-ß (Aß) plaques and neurofibrillary tangles (NFTs), in the brain offer poor to moderate success. Detection and imaging of biomarkers that cause additional traits of pathophysiological aberrations in the brain are invaluable to monitor early disease onset and progression of AD pathology. The pathological hallmark of AD is associated with generation of excessive reactive oxygen species (ROS) in the brain, which aggravate oxidative stress and inflammation. ROS production involves elevated levels of hypochlorous acid (HOCl) and can serve as one of the potential biomarkers for the diagnosis of AD. We report the design, synthesis, and characterization of switchable coumarin-morpholine (CM) conjugates as off-on fluorescence probes for the specific detection of HOCl produced and proximally localized with amyloid plaques. The nonfluorescent thioamide probe CM2 undergoes regioselective transformation to fluorescent amide probe CM1 in the presence of HOCl (∼90-fold fluorescence enhancement and 0.32 quantum yield) with high selectivity and sensitivity (detection limit: 0.17 µM). The excellent cellular uptake and blood-brain barrier (BBB) crossing ability of CM2 allowed unambiguous and differential detection, imaging, and quantification of HOCl in cellular milieu and in the wild type (WT) and AD mouse brains. This study demonstrates the elevated level of HOCl in the AD mouse brain and the potential to expand the repertoire of biomarkers for the diagnosis of AD.

Small Molecule Inhibits Metal-Dependent and -Independent Multifaceted Toxicity of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most devastating forms of dementia, without reliable treatments to cure, delay the onset, or prevent the disease progression. The proposed toxic mechanisms of AD include amyloidogenesis of amyloid ß (Aß), metal ion dyshomeostasis, redox active metal-Aß inclusion complex formation, and generation of excessive reactive oxygen and nitrogen species (ROS and RNS). The imbalance in redox homeostasis causes oxidative stress, DNA damage, mitochondrial dysfunction, and inflammation, which collectively become a major hurdle in the development of effective therapeutic agents for multifactorial AD. This necessitates a multifunctional strategy to develop effective therapeutic agents to inhibit multifaceted toxicity. In this context, we report a rational design, synthesis, and detailed study to identify a small molecule multifunctional modulator (MFM) inspired by the human origin tripeptide. The lead, MFM 4, chelates and sequesters metal ions, disrupts their redox cycles, prevents excessive ROS production and oxidative stress, ameliorates oxidative DNA damage and mitochondrial dysfunction, and modulates Nrf2 protein signaling under oxidative stress conditions by eliminating the toxic stress elements. The MFM 4 was found to inhibit metal-dependent and -independent Aß aggregation and qualified as a suitable candidate to inhibit Aß-induced neuronal toxicity. The NMR spectroscopy study revealed molecular-level interactions of 4 with Aß42, which explain the mechanism of aggregation inhibition. Furthermore, 4 effectively inhibited inflammation as revealed by reduction in nitric oxide (NO) production in LPS-activated glial cells. These key features make 4 a potential MFM platform to develop therapeutic agents for metal (Cu, Zn and Fe)-dependent and -independent multifaceted Aß toxicity of AD.

CO2 fluxes from aquaculture ponds of a tropical wetland: Potential of multiple lime treatment in reduction of CO2 emission.

Partial pressure of CO2 in water [pCO2(water)] and air-water CO2 flux were estimated in two aquaculture ponds (one received no lime treatment (NTP) and in the other lime treatment was performed (LTP) four times a year) every month throughout an annual cycle, situated in East Kolkata Wetlands, a Ramsar Site in eastern India. It was hypothesized that lime treatment can potentially lower the pCO2(water) in aquaculture ponds and hence make these aquatic bodies sinks for CO2. The results portrayed that NTP acted as a source of CO2 throughout the year (annual mean: 1929 ±â€¯1397 µmol m-2 h-1), whereas, LTP acted as CO2 sinks post lime addition (monthly mean ranged from -366 ±â€¯16 to -449 ±â€¯32 µmol m-2 h-1), though the effect of lime addition was found to diminish by the next month and it acted as source for CO2 in the months when no lime treatment was done (LTP annual mean: 1010 ±â€¯1617 µmol m-2 h-1). Lime treatment increased the pH level and reduced the turbidity which facilitated optimum photosynthesis and the productivity increased rapidly. Beyond the critical pH value of 8.9-9.0, the pCO2(water) values became under-saturated with respect to atmospheric CO2 concentration. The effect of lime treatment was not found to prevail in the following months as a steady source of sewage from the Kolkata metropolis which feeds these aquaculture constantly bring in a huge carbon source both in inorganic and organic form. As soon as the flocculation effect of the lime dies off, the water column starts becoming turbid again which aids in converting the system into a net heterotrophic one from a net autotrophic. Based on the results we could successfully accept our hypothesis that lime treatment can not only reduce the CO2 emission but also make the system a CO2 sink.