Discovery Pool Research Articles

Recent efforts for drug identification from phytochemicals against SARS-CoV-2: Exploration of the chemical space to identify druggable leads

Nature, which remains a central drug discovery pool, is always looked upon to find a putative druggable lead. The natural products and phytochemical derived from plants are essential during a global health crisis. This class represents one of the most practical and promising approaches to decrease pandemic's intensity owing to their therapeutic potential. The present manuscript is therefore kept forth to give the researchers updated information on undergoing research in allied areas of natural product-based drug discovery, particularly for Covid-19 disease. The study briefly shreds evidence from in vitro and in silico researches done so far to find a lead molecule against Covid-19. Following this, we exhaustively explored the concept of chemical space and molecular similarity parameters for the drug discovery about the lead(s) generated from in silico-based studies. The comparison was drawn using FDA-approved anti-infective agents during 2015–2020 using key descriptors to evaluate druglike properties. The outcomes of results were further corroborated using Molecular Dynamics studies which suggested the outcomes in alignment with chemical space ranking. In a nutshell, current research work aims to provide a holistic strategic approach to drug design, keeping in view the identified phytochemicals against Covid-19.

A Cross-Institutional Study of eBook Demand-Driven Acquisition (DDA) Use and Efficacy of Eight Large Academic Libraries

This study is the first of its kind to analyze and compare demand-driven acquisition (DDA) ebook programs on a large scale by using eight academic libraries. The purpose is to understand which factors contribute to successful collection management practices and sustainability. Study findings also offer insight into weeding practices and suggest that ebooks removed from the discovery pool too soon may impact service to library users. Furthermore, findings based on formula analysis show that return on investment (ROI) for serviceable content is better achieved through a sustained straight DDA model without short-term loans.

Neutrophil myeloperoxidase harbors distinct site-specific peculiarities in its glycosylation

Anti-neutrophil cytoplasmic autoantibodies (ANCAs) are directed against lysosomal components of neutrophils. ANCAs directed to proteinase 3 and myeloperoxidase (MPO) in particular are associated with distinct forms of small vessel vasculitides. MPO is an abundant neutrophil-derived heme protein that is part of the antimicrobial defense system. The protein is typically present in the azurophilic granules of neutrophils, but a large portion may also enter the extracellular space. It remains unclear why MPO is frequently the target of antibody-mediated autoimmune responses. MPO is a homodimeric glycoprotein, posttranslationally modified with complex sugars at specific sites. Glycosylation can strongly influence protein function, affecting its folding, receptor interaction, and backbone accessibility. MPO potentially can be heavily modified as it harbors 5 putative N-glycosylation sites (10 in the mature dimer). Although considered important for MPO structure and function, the full scope and relative abundance of the glycans attached to MPO is unknown. Here, combining bottom-up glycoproteomics and native MS approaches, we structurally characterized MPO from neutrophils of healthy human donors. We quantified the relative occupancy levels of the glycans at each of the five sites and observed complex heterogeneity and site-specific glycosylation. In particular, we detected glycosylation phenotypes uncommon for glycoproteins in the extracellular space, such as a high abundance of phosphorylated high-mannose species and severely truncated small glycans having the size of paucimannose or smaller. We hypothesize that the atypical glycosylation pattern found on MPO might contribute to its specific processing and presentation as a self-antigen by antigen-presenting cells.

Diversity of microbial carbohydrate-active enzymes in Danish anaerobic digesters fed with wastewater treatment sludge

BackgroundImproved carbohydrate-active enzymes (CAZymes) are needed to fulfill the goal of producing food, feed, fuel, chemicals, and materials from biomass. Little is known about how the diverse microbial communities in anaerobic digesters (ADs) metabolize carbohydrates or which CAZymes that are present, making the ADs a unique niche to look for CAZymes that can potentiate the enzyme blends currently used in industry.ResultsEnzymatic assays showed that functional CAZymes were secreted into the AD environments in four full-scale mesophilic Danish ADs fed with primary and surplus sludge from municipal wastewater treatment plants. Metagenomes from the ADs were mined for CAZymes with Homology to Peptide Patterns (HotPep). 19,335 CAZymes were identified of which 30% showed 50% or lower identity to known proteins demonstrating that ADs make up a promising pool for discovery of novel CAZymes. A function was assigned to 54% of all CAZymes identified by HotPep. Many different α-glucan-acting CAZymes were identified in the four metagenomes, and the most abundant family was glycoside hydrolase family 13, which contains α-glucan-acting CAZymes. Cellulytic and xylanolytic CAZymes were also abundant in the four metagenomes. The cellulytic enzymes were limited almost to endoglucanases and β-glucosidases, which reflect the large amount of partly degraded cellulose in the sludge. No dockerin domains were identified suggesting that the cellulytic enzymes in the ADs studied operate independently. Of xylanolytic CAZymes, especially xylanases and β-xylosidase, but also a battery of accessory enzymes, were present in the four ADs.ConclusionsOur findings suggest that the ADs are a good place to look for novel plant biomass degrading and modifying enzymes that can potentiate biological processes and provide basis for production of a range of added-value products from biorefineries.

Demand-Driven Acquisition E-books Have Equal Cost Per Use as Print, but DDA Has Much More Active Use Overall

A Review of:
 Downey, K., Zhang, Y., Urbano, C., & Klinger, T. (2014). A comparative study of print book and DDA e-book acquisition and use. Technical Services Quarterly, 31 (2), 139-160. http://dx.doi.org/10.1080/07317131.2014.875379
 
 Abstract
 
 Objective – To compare usage of demand-driven acquisition (DDA) e-books with print books to help determine if one acquisition model better serves the needs of library users and return on investment.
 
 Design – Case study.
 
 Setting – Library system of a large American public university. 
 
 Subjects – 22,018 DDA e-book discovery records, 456 purchased e-book records, and 20,030 print item records were examined.
 
 Method – The researchers examined usage statistics, circulation statistics, and cost measures of DDA e-books and print books. E-books were purchased in 2012 and print books were purchased by the start of the DDA project (January 2012).
 
 Main Results – All but one of the 456 DDA-triggered e-books had repeated use within the first year, totalling 2,484 user sessions. 90% of the triggered e-books had 2-9 user sessions, and over half had at least 4 user sessions. E-books were most used in classes N (fine arts), P (Language and Literature), and R (Medicine). E-books in T (Technology) had a lower percentage of user sessions compared to other subject areas. 712 (3.2%) of the e-books in the discovery pool were used without triggering a purchase. Usage of e-books in the discovery pool (those used but not triggering a purchase) showed a consistent use of e-books by subject. E-books in Class B (Philosophy, Psychology, Religion) were used more in the discovery pool without actually being purchased, suggesting a light use of a wide range of books in this subject area. In contrast, Class R (Medicine) saw less use in the discovery pool than what was actually purchased, suggesting heavier and more focused use of triggered e-books in this area. Only 62.5% of the 20,030 purchased print books included in the study were used in the first 1 to 2.5 years they were added to the collection (i.e., 37.5% were not used in that time period). Half of the print books were used no more than once (once or no use), and more than 90% were used fewer than 10 times. Print books in Class Q (Science) contributed to only 7.5% of the total circulations, suggesting print books are underused in this subject area. 10.2% of total circulation of print books in Class R (Medicine) suggests print books are better used in this area. Print acquisition and use occur more often in classes N (Fine Arts) and P (Language and Literature). The average cost for DDA e-books was of $98.52 per book. The average price per print book was $59.53. The unit cost per print book was $17.73 per use. Depending on various measures, cost per use for e-books ranged from $17.73 to $29.15 per use. (If the measurement included the free use of non-triggered DDA books, the cost per use was $18.07, essentially the same as the print cost).
 
 Conclusion – Both print books and DDA e-books are proportionately distributed across most subject areas. Although DDA and print cost per use are equal, DDA leads to much more active use overall.

Enhancing in silico protein-based vaccine discovery for eukaryotic pathogens using predicted peptide-MHC binding and peptide conservation scores.

Given thousands of proteins constituting a eukaryotic pathogen, the principal objective for a high-throughput in silico vaccine discovery pipeline is to select those proteins worthy of laboratory validation. Accurate prediction of T-cell epitopes on protein antigens is one crucial piece of evidence that would aid in this selection. Prediction of peptides recognised by T-cell receptors have to date proved to be of insufficient accuracy. The in silico approach is consequently reliant on an indirect method, which involves the prediction of peptides binding to major histocompatibility complex (MHC) molecules. There is no guarantee nevertheless that predicted peptide-MHC complexes will be presented by antigen-presenting cells and/or recognised by cognate T-cell receptors. The aim of this study was to determine if predicted peptide-MHC binding scores could provide contributing evidence to establish a protein’s potential as a vaccine. Using T-Cell MHC class I binding prediction tools provided by the Immune Epitope Database and Analysis Resource, peptide binding affinity to 76 common MHC I alleles were predicted for 160 Toxoplasma gondii proteins: 75 taken from published studies represented proteins known or expected to induce T-cell immune responses and 85 considered less likely vaccine candidates. The results show there is no universal set of rules that can be applied directly to binding scores to distinguish a vaccine from a non-vaccine candidate. We present, however, two proposed strategies exploiting binding scores that provide supporting evidence that a protein is likely to induce a T-cell immune response–one using random forest (a machine learning algorithm) with a 72% sensitivity and 82.4% specificity and the other, using amino acid conservation scores with a 74.6% sensitivity and 70.5% specificity when applied to the 160 benchmark proteins. More importantly, the binding score strategies are valuable evidence contributors to the overall in silico vaccine discovery pool of evidence.

A Comparative Study of Print Book and DDA Ebook Acquisition and Use

In January 2012, Kent State University Libraries implemented a six-month pilot project for a Demand-Driven Acquisitions (DDA) ebook purchasing model that uses a combination of the acquisition services provided by the primary book jobber (YBP) and the access services provided by a well-known ebook distributer (eBrary). Using the book jobber mediated DDA model provided the library with selected discovery records that closely matched specifications of the library's print approval plan. This report provides an assessment of the DDA acquisition model as compared to that of the print books approval model in terms of budget, costs, workflow, subjects, publishers, and publication dates. Because DDA empowers library users to choose which ebooks are purchased based on actual use, this assessment also compares ebook usage from a DDA discovery pool with print book circulation of an equivalent amount of recent print acquisitions. The results of this study will help answer some of the key questions about the DDA acquisition model: (1) How does DDA align the library's collection with current user requirements? (2) Does DDA lead to more active use of library book collection? (3) Is DDA cost effective as an acquisition model? (4) What issues are associated with DDA, and how may these issues be addressed?

Transcriptome of the dead: characterisation of immune genes and marker development from necropsy samples in a free-ranging marine mammal

BackgroundTranscriptomes are powerful resources, providing a window on the expressed portion of the genome that can be generated rapidly and at low cost for virtually any organism. However, because many genes have tissue-specific expression patterns, developing a complete transcriptome usually requires a 'discovery pool' of individuals to be sacrificed in order to harvest mRNA from as many different types of tissue as possible. This hinders transcriptome development in large, charismatic and endangered species, many of which stand the most to gain from such approaches. To circumvent this problem in a model pinniped species, we 454 sequenced cDNA from testis, heart, spleen, intestine, kidney and lung tissues obtained from nine adult male Antarctic fur seals (Arctocephalus gazella) that died of natural causes at Bird Island, South Georgia.ResultsAfter applying stringent quality control criteria based on length and annotation, we obtained 12,397 contigs which, in combination with 454 data previously obtained from skin, gave a total of 23,096 unique contigs. Homology was found to 77.0% of dog (Canis lupus familiaris) transcripts, suggesting that the combined assembly represents a substantial proportion of this species' transcriptome. Moreover, only 0.5% of transcripts revealed sequence similarity to bacteria, implying minimal contamination, and the percentage of transcripts involved in cell death was low at 2.6%. Transcripts with immune-related annotations were almost five-fold enriched relative to skin and represented 13.2% of all spleen-specific contigs. By reference to the dog, we also identified transcripts revealing homology to five class I, ten class II and three class III genes of the Major Histocompatibility Complex and derived the putative genomic distribution of 17,121 contigs, 2,119 in silico mined microsatellites and 9,382 single nucleotide polymorphisms.ConclusionsOur findings suggest that transcriptome development based on samples collected post mortem may greatly facilitate genomic studies, not only of marine mammals but also more generally of species that are of conservation concern.

Genome wide SNP discovery, analysis and evaluation in mallard (Anas platyrhynchos)

BackgroundNext generation sequencing technologies allow to obtain at low cost the genomic sequence information that currently lacks for most economically and ecologically important organisms. For the mallard duck genomic data is limited. The mallard is, besides a species of large agricultural and societal importance, also the focal species when it comes to long distance dispersal of Avian Influenza. For large scale identification of SNPs we performed Illumina sequencing of wild mallard DNA and compared our data with ongoing genome and EST sequencing of domesticated conspecifics. This is the first study of its kind for waterfowl.ResultsMore than one billion base pairs of sequence information were generated resulting in a 16× coverage of a reduced representation library of the mallard genome. Sequence reads were aligned to a draft domesticated duck reference genome and allowed for the detection of over 122,000 SNPs within our mallard sequence dataset. In addition, almost 62,000 nucleotide positions on the domesticated duck reference showed a different nucleotide compared to wild mallard. Approximately 20,000 SNPs identified within our data were shared with SNPs identified in the sequenced domestic duck or in EST sequencing projects. The shared SNPs were considered to be highly reliable and were used to benchmark non-shared SNPs for quality. Genotyping of a representative sample of 364 SNPs resulted in a SNP conversion rate of 99.7%. The correlation of the minor allele count and observed minor allele frequency in the SNP discovery pool was 0.72.ConclusionWe identified almost 150,000 SNPs in wild mallards that will likely yield good results in genotyping. Of these, ~101,000 SNPs were detected within our wild mallard sequences and ~49,000 were detected between wild and domesticated duck data. In the ~101,000 SNPs we found a subset of ~20,000 SNPs shared between wild mallards and the sequenced domesticated duck suggesting a low genetic divergence. Comparison of quality metrics between the total SNP set (122,000 + 62,000 = 184,000 SNPs) and the validated subset shows similar characteristics for both sets. This indicates that we have detected a large amount (~150,000) of accurately inferred mallard SNPs, which will benefit bird evolutionary studies, ecological studies (e.g. disentangling migratory connectivity) and industrial breeding programs.

Results of California Exploration during the War Period: ABSTRACT

The paper continues the work Roy Barnes published in the A.A.P.G. Bulletin of October, 1940, on through the war period with emphasis on discoveries of the first 9 months of 1945. The trends of geophysical activity, geological employment in exploration, and the number of A.A.P.G. members in California are shown and compared with the price curve. A pronounced increase in A.A.P.G. membership is found with only a slight increase in employment in the seventeen companies considered. It is thought the employment trend is not representative as many of the smaller companies not considered have added to their staffs. The seismograph activity has fluctuated seasonally but has averaged a level trend. Wildcat drilling as shown by the dry-hole curve has increased and broken previous records both in 1943 and 1944. The lesser increase in number of currently active wildcats End_Page 128------------------------------ is ascribed to increased efficiency in shortening rigging-up and shut-down periods due to greater demand for rigs and crews. A clear correlation is shown between the number of wildcats drilled and the number of discoveries made. The less obvious correlation between geological employment and discoveries may be due to the lapse of time between the working-out of a play and the drilling of it, in some cases 5 or 10 years. The increased demand and price of dry gas is reflected in the increasing number of gas field discoveries. The correlation of reserves, production, and new reserves by discovery is discussed. The new reserves discovered have failed to keep pace with the production. The production, which reached a new high of 311 million barrels in 1944 and possibly will reach 315 million in 1945, has been maintained by increased development drilling and the discovery of new pools and extensions. By the end of the war the California reserves had declined only 185 million barrels, from 3533 million in 39 to 3348 million in January, 1945. The effect of Order M68 on development drilling is well marked by a slump, while practically no effect is visible on wildcat drilling. As was intended, that order provided materials to keep up the pace of exploration at the expense of development drilling. The prompt recover of development activity by the fall of 1942 and its rapid increase from then through the war is illustrated by the curve. The amount of oil found by wildcatting alone, that is, the amount of oil in the discovery pool only of the fields is compared with the total ultimate by years. The curve shows that approximately three-eighths of the oil has been in pools discovered by later exploratory drilling. Also, it is seen that the discoveries in California have come in steps of half billion or more size additions to reserves at intervals of 8 to 10 years which are timed by advances in geologic exploration, drilling technique, and seismic exploration. The present year should be the period for another advance in discoveries according to the chart, but so far has not differed from the last 6 or 7 years in volume of oil found. The writer estimates roughly 25 million barrels of oil as the reserves of the new fields. With the data so far in hand no estimate of the new gas fields or of the new pools and extensions can be given. The various exploration methods or combinations of them leading to the drilling of the dry holes and discoveries are compared graphically. The chart showed 20 wildcats to be successful out of a total of 202 drilled. Of these only sixteen will eventually be regarded as having found fields rather than extensions, and five of these were of dubious commercial value. The greatest footage and number of wells were drilled on subsurface work, with both seismic and surface work less and about equal. Other methods and combinations had much less footage. The over-all wildcat success percentage was 10.2%. New-pool tests were 31% successful and outposts 42% successful. It appears that at the present rate 1945 will end with somewhat less wildcat footage but with a greater number of wells drilled. O her types of exploratory wells will exceed substantially 1944 both in footage and number. End_of_Article - Last_Page 129------------