Advances in ophthalmic drug delivery

Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient’s lifetime

INFECTION OF GASTRO-INTESTINAL TRACT BY SARS-CoV-2 AND ITS POTENTIAL FOR FAECAL-ORAL TRANSMISSION: A LITERATURE REVIEW

Context: SARS-CoV-2, has already affected more than 180 countries. 3,175,207 confirmed cases and 224,173 deaths due to the disease were reported worldwide till 1st May 2020. WHO has declared it a Public Health Emergency of International Concern. Aims: To present information from worldwide literature on infection of gastro-intestinal tract by SARS-CoV-2 and its potential for faecal-oral transmission. Material and Methods: Literature search was carried out using Google Scholar and PubMed in 3rd week of April, 2020. Search terms used were “SARS-CoV-2” or “COVID-19” or “New Coronavirus” or “Coronavirus” in title and “Transmission” or “Faecal” or “Oral” anywhere in the article. Studies from the year 2019 to 2020 published in “English” language were included in the search. Results: 15 studies were found relevant and were included in the review. Studies reported that SARS-CoV-2 infects and replicates in gastro-intestinal tract and manifests enteric symptoms. Viral RNA is excreted in stool. Fecal samples were found to be positive for the viral RNA for many days even after respiratory samples become negative. Virus has been detected in anal swabs and live virus could be successfully isolated from stool specimen. The virus was also reported to be viable in the environment for many days. Conclusions: SARS-CoV-2 can potentially be transmitted by faecal-oral route. The transmission can occur even after respiratory symptoms subside and respiratory tract samples test negative for the virus. Appropriate policy response is needed for awareness, testing, discharge and quarantine of patients to prevent spread of the disease. Keywords--SARS-CoV-2, Coronavirus Outbreak, COVID-19, New Coronaviru

Phytochemicals against COVID-19 and a gap in clinical investigations: An outlook

The novel coronavirus 2019 (COVID-19) has presented an unexpected pandemic that has triggered severe panic among people worldwide. In this direction, nations are maximizing their efforts to battle the disease and lower illness. Plants that produce numerous bioactive compounds might help develop and keep immunity against chronic diseases and COVID-19. Medicinal plant-based treatments are trendy in rural and tribal communities, mainly as an outcome of the increased scalability, which causes them to be cheaper and affordable compared to present-day medication. Furthermore, additional research on the antiviral possibility of healing plants shown that plant extracts with incredibly energetic secondary metabolites are competent to interrupt the replication of numerous very pathogenic viruses. But the testing and clinical trials take a very long time. This review discusses the gap in clinical studies with available phytochemicals and the possible ways to cover the same

New mutations at the imprinted Gnas cluster show gene dosage effects of Gsα in postnatal growth and implicate XLαs in bone and fat metabolism, but not in suckling

The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLαs, XLN1, and ALEX or a double dose of maternally expressed Gsα to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsα, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsα and loss of expression of XLαs and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLαs, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLαs. This is, to our knowledge, the first report describing a role for XLαs in bone metabolism. We propose that XLαs is involved in the regulation of bone and adipocyte metabolism

Biochemical composition of potato biowaste of popular North Indian cultivars

Potato is among the top processed vegetables, and its demand is continuously on the rise. Moreover, by the unit that peels are produced, significant issues associated with managing substantial volumes of solvents, impractical astounding scale drying out functions, in addition to lowering capital expenses render these remedies unfeasible. Additionally, isolation of helpful metabolites from potato are bound on the usage authorized as food quality applications. The current study's objective was to estimate the peel biochemical composition of potato cultivars suitable for cultivation in the Ranch district of Jharkhand state in India. The highest amount of chlorogenic acid (1.13 mg/g FW) and dry matter (17.90%) was determined in the variety Kufri Sindhuri. The chlorogenic acid content and the peel dry matter were determined to be significantly correlated with each other. The highest value for the phenolic content of the potato peel was determined for the variety Kufri Lalima. Simultaneously, the reducing sugars were most elevated in the peel of variety Kufri Pukhraj and starch content in the peel of variety Kufri Purkhraj. Overall, our work highlights the biochemical composition of potato peel and this information can be targeted on the potential usage of potato peel usage for industrial products formulation

Effect of poplar and eucalyptus based agroforestry system on soil biochemistry

126-130The field experiment was conducted during the winter season of 2016-17 at the experimental site of Agroforestry Research Centre, G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand. Poplar and eucalyptus were intercropped with different wheat varieties (UP-2526, UP-2565, UP-2628, and DPW-621-50). After harvesting the wheat crop, the soil sampling was performed to determine the soil parameters like electrical conductivity (EC), organic carbon and the minerals content. Nitrogen, phosphorus and potassium content and other biochemical constituents were higher in the agroforestry system as compared to the open farming system. A high soil pH (7. 53) was found in an open farming system and lower pH in an agroforestry system. Soil EC in the agroforestry system was slightly higher than the open farming system. Organic carbon was maximum (1. 33%) under the poplar agroforestry system compared to the eucalyptus based agroforestry system. Overall, this study determines the effect of poplar and eucalyptus based agroforestry systems on soil biochemistry

Control of sulphide during anaerobic treatment of S-containing wastewaters by adding limited amounts of oxygen or nitrate

Sulphide generated during anaerobic treatment of S-containing wastewaters represents an environmental problem. Adding limited amounts of oxygen or nitrate (or nitrite) to biologically (or chemically) oxidise sulphide forms a simple process level strategy to control this problem. This short review evaluates the feasibility and limitations of this strategy on the basis of the results of bioreactor studies.Sulphide generated during anaerobic treatment of S-containing wastewaters represents an environmental problem. Adding limited amounts of oxygen or nitrate (or nitrite) to biologically (or chemically) oxidise sulphide forms a simple process level strategy to control this problem. This short review evaluates the feasibility and limitations of this strategy on the basis of the results of bioreactor studies.Spanish Ministry of Education and Science; AEA Technology Environment; Nova Energie; The Swedish Gas Centre; University of Southern Denmark

Critical mutation rate has an exponential dependence on population size for eukaryotic-length genomes with crossover

The critical mutation rate (CMR) determines the shift between survival-of-the-fittest and survival of individuals with greater mutational robustness (“flattest”). We identify an inverse relationship between CMR and sequence length in an in silico system with a two-peak fitness landscape; CMR decreases to no more than five orders of magnitude above estimates of eukaryotic per base mutation rate. We confirm the CMR reduces exponentially at low population sizes, irrespective of peak radius and distance, and increases with the number of genetic crossovers. We also identify an inverse relationship between CMR and the number of genes, confirming that, for a similar number of genes to that for the plant Arabidopsis thaliana (25,000), the CMR is close to its known wild-type mutation rate; mutation rates for additional organisms were also found to be within one order of magnitude of the CMR. This is the first time such a simulation model has been assigned input and produced output within range for a given biological organism. The decrease in CMR with population size previously observed is maintained; there is potential for the model to influence understanding of populations undergoing bottleneck, stress, and conservation strategy for populations near extinction

Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition

Protein phosphatase 2A (PP2A) holoenzymes target broad substrates by recognizing short motifs via regulatory subunits. PP2A methylesterase 1 (PME-1) is a cancer-promoting enzyme and undergoes methylesterase activation upon binding to the PP2A core enzyme. Here, we showed that PME-1 readily demethylates different families of PP2A holoenzymes and blocks substrate recognition in vitro. The high-resolution cryoelectron microscopy structure of a PP2A-B56 holoenzyme–PME-1 complex reveals that PME-1 disordered regions, including a substrate-mimicking motif, tether to the B56 regulatory subunit at remote sites. They occupy the holoenzyme substrate-binding groove and allow large structural shifts in both holoenzyme and PME-1 to enable multipartite contacts at structured cores to activate the methylesterase. B56 interface mutations selectively block PME-1 activity toward PP2A-B56 holoenzymes and affect the methylation of a fraction of total cellular PP2A. The B56 interface mutations allow us to uncover B56-specific PME-1 functions in p53 signaling. Our studies reveal multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile PME-1 activities derived from coupling substrate-mimicking motifs to dynamic structured cores

Diversification of rice with pigeonpea in a rice-wheat cropping system on a Typic Ustochrept: effect on soil fertility, yield and nutrient use efficiency

Continuous adoption of rice-wheat cropping system (RWCS) has led to depletion of inherent soil fertility resulting in a serious threat to its sustainability in the Indo-Gangetic plain region (IGPR) of India. The inclusion of legumes in RWCS assumes a great significance to restore soil fertility. But farmers in the IGPR rarely grow legumes in the system. We, therefore, carried out farmers' participatory diagnostic survey in the Upper Gangetic plain zone (UGP) to understand farmers' fertilizer management practices for wheat (Trititicum aestivum L. Emend Fiori & Paol) following rice (Oryza sativa L.) or pigeonpea (Cajanus cajan (L.) Millsp). The survey indicated that most of the farmers in UGP grew pigeonpea in place of rice under RWCS as only a break crop at a 2-3 year interval. The farmers applied, on average, 11 kg N ha-1 and 24 kg P ha-1 to wheat sown after rice, and 12 kg N ha-1 and 19 kg P ha-1 to wheat sown after pigeonpea. Wheat yields, however, were lower (3.3 t ha-1) when sown after pigeonpea than after rice (3.7 t ha-1). The survey was followed by a field experiment at Modipuram (29°4′N), Meerut, India that continued during the three consecutive years (1998-1999 to 2000-2001) to examine the effect of inclusion of pigeonpea in place of rice on soil fertility, N and P use efficiency and yields of wheat. In 1998-1999, wheat yields after pigeonpea were lower than after rice, but improved significantly (p<0.05) by 11.4-15.1% in pigeonpea plots compared with those in rice plots during 1999-2000 and 2000-2001, respectively. The use efficiency of applied N and P fertilizers in wheat, measured as agronomic efficiency and apparent recovery, was increased with combined use of fertilizer N and P at recommended rate, and also with inclusion of pigeonpea in place of rice. The post-wheat harvest NO3-N in soil profile beyond 45 cm depth was significantly greater under rice-wheat system than under pigeonpea-wheat system, suggesting that inclusion of pigeonpea may help in minimizing NO3-N leaching to deeper profile layers beyond root zone. Similarly, in the treatments receiving both 120 kg N and 26 kg P ha-1, NO3-N beyond 45 cm soil depth was lower compared to those receiving N or P alone. Inclusion of pigeonpea in place of rice enhanced carbon accumulation in the soil profile. The available P content was, however, invariably low under pigeonpea plots as compared to that under rice. With continuous rice-wheat cropping, the bulk density (BD) of soil was increased, especially in the 30-45 cm soil profile. Inclusion of pigeonpea in the system not only helped maintaining soil BD at initial level in the surface (0-15 cm) soil layers, but also in decreasing (p<0.05) BD in sub-surface layers (15-30 cm and 30-45 cm). Compared to rice, a statistically significant (p<0.05) positive effect of pigeonpea on root volume (58%) and root weight (99.5%) of succeeding wheat was also recorded. The net economic returns under pigeonpea-wheat system were greater compared with rice-wheat syste