CPPsite: a curated database of cell penetrating peptides

Delivering drug molecules into the cell is one of the major challenges in the process of drug development. In past, cell penetrating peptides have been successfully used for delivering a wide variety of therapeutic molecules into various types of cells for the treatment of multiple diseases. These peptides have unique ability to gain access to the interior of almost any type of cell. Due to the huge therapeutic applications of CPPs, we have built a comprehensive database ‘CPPsite’, of cell penetrating peptides, where information is compiled from the literature and patents. CPPsite is a manually curated database of experimentally validated 843 CPPs. Each entry provides information of a peptide that includes ID, PubMed ID, peptide name, peptide sequence, chirality, origin, nature of peptide, sub-cellular localization, uptake efficiency, uptake mechanism, hydrophobicity, amino acid frequency and composition, etc. A wide range of user-friendly tools have been incorporated in this database like searching, browsing, analyzing, mapping tools. In addition, we have derived various types of information from these peptide sequences that include secondary/tertiary structure, amino acid composition and physicochemical properties of peptides. This database will be very useful for developing models for predicting effective cell penetrating peptides

Sox2 Is Essential for Formation of Trophectoderm in the Preimplantation Embryo

In preimplantation mammalian development the transcription factor Sox2 (SRY-related HMG-box gene 2) forms a complex with Oct4 and functions in maintenance of self-renewal of the pluripotent inner cell mass (ICM). Previously it was shown that Sox2-/- embryos die soon after implantation. However, maternal Sox2 transcripts may mask an earlier phenotype. We investigated whether Sox2 is involved in controlling cell fate decisions at an earlier stage.We addressed the question of an earlier role for Sox2 using RNAi, which removes both maternal and embryonic Sox2 mRNA present during the preimplantation period. By depleting both maternal and embryonic Sox2 mRNA at the 2-cell stage and monitoring embryo development in vitro we show that, in the absence of Sox2, embryos arrest at the morula stage and fail to form trophectoderm (TE) or cavitate. Following knock-down of Sox2 via three different short interfering RNA (siRNA) constructs in 2-cell stage mouse embryos, we have shown that the majority of embryos (76%) arrest at the morula stage or slightly earlier and only 18.7-21% form blastocysts compared to 76.2-83% in control groups. In Sox2 siRNA-treated embryos expression of pluripotency associated markers Oct4 and Nanog remained unaffected, whereas TE associated markers Tead4, Yap, Cdx2, Eomes, Fgfr2, as well as Fgf4, were downregulated in the absence of Sox2. Apoptosis was also increased in Sox2 knock-down embryos. Rescue experiments using cell-permeant Sox2 protein resulted in increased blastocyst formation from 18.7% to 62.6% and restoration of Sox2, Oct4, Cdx2 and Yap protein levels in the rescued Sox2-siRNA blastocysts.We conclude that the first essential function of Sox2 in the preimplantation mouse embryo is to facilitate establishment of the trophectoderm lineage. Our findings provide a novel insight into the first differentiation event within the preimplantation embryo, namely the segregation of the ICM and TE lineages

Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles

The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work

JavaGRID: Providing Simplified Access to Widely Distributed Computing

Presented for Consideration to the Conference on High Performance Distributed Computing Samuel H. Russ, Srikanth Batchu, Sonetra Howard, and Saneedp Musinipally Mississippi State University NSF Engineering Research Center for Computational Field Simulation Abstract ---- The era of rapid, easy access to remote computer resources is rapidly ap- proaching. Systems and collaborative efforts have been launched to experiment and determine how widely distributed, loosely coupled computing resources can be harnessed and man- aged efficiently and effectively. Such systems are sometimes called a "grid" or "information power grid". This paper discusses a grid architecture that promotes widely distributed com- puting among scientific programmers by making both access to remote resources and admins- tiration of remote users extremely simple. The architecture leverages the portability of Java, the Web, and MPI, and provides a platform for experimenting with regional--scale grids and "intrag..

High-Condensed Tannin Diet and Transportation Stress in Goats: Effects on Physiological Responses, Gut Microbial Counts and Meat Quality

Feeding condensed tannin (CT)-containing diets such as sericea lespedeza (Lespedeza cuneata) and reducing stress have been reported to improve meat quality and food safety in goats. In a completely randomized design with split-plot, thirty-six uncastrated male Spanish goats were assigned to 3 dietary treatments (n = 12/treatment): ground ‘Serala’ sericea lespedeza hay (SER), bermudagrass (Cynodon dactylon) hay (BG), or bermudagrass hay—dewormed goats (BG-DW; Control) at 75% of intake, with a corn-based supplementation (25%) for 8 weeks. Prior to slaughter, goats were either transported for 90 min to impose stress or held in pens. Basophil counts were lower (p < 0.01) in the SER group compared to BG or BG-DW groups suggesting a better anti-inflammatory capacity due to polyphenols in the SER diet. Compared to BG-DW group, cortisol level was higher (p < 0.05) and norepinephrine was lower (p < 0.05) in the SER group. The SER group had the lowest aerobic plate counts (APC) in both rumen and rectum (p < 0.01). Longissimus dorsi muscle initial pH was not affected by diet or stress. Feeding sericea hay to goats may have beneficial effects, such as enhanced antioxidant and anti-inflammatory properties during stress and reduced gut microbial counts, without changing meat quality characteristics

Plasma metabolomic profiles as affected by diet and stress in Spanish goats

Abstract The effects of high-condensed tannin (CT) diet combined with preslaughter stress have not been studied at the metabolome level in goats. This study was conducted to determine the effects of feeding sericea lespedeza (SL; Lespedeza cuneata), a high-CT legume, and transportation stress on plasma metabolome in goats. Uncastrated male Spanish goats (age = 8 months; BW = 26.0 ± 0.48 kg) were either fed ground ‘Serala’ SL hay (SER), bermudagrass (Cynodon dactylon) hay (BG), or bermudagrass hay-dewormed goats (BG-DW; Control) at 75% of intake, with a corn-based supplementation (25%) for 8 weeks (n = 12/Diet). At the end of the trial, goats were subjected to one of two stress treatments (ST): transported for 90 min to impose stress (TS) or held in pens (NTS) before slaughtering, in two replicates. Live and carcass weights, and blood samples were collected at 0, 30, 60 and 90 min of transportation or holding time (Time). The data were analyzed using MIXED procedures in SAS and metabolomics data were analyzed using the R software. When measured after ST, SER group had the lowest body weight (P < 0.05) among the three diet groups. Carcass weights were high in the BG-DW, low in SER, and intermediate in BG group. Plasma creatine concentrations decreased over Time (P < 0.01) in the TS goats in all diet groups. Meat crude protein percentages were higher (P < 0.05) in SER (22.5 ± 0.22) and BG-DW (22.3 ± 0.22) groups compared to the BG group (21.6 ± 0.22). At the metabolome level, SER group had the lowest (P < 0.05) glycine, alanine, threonine, taurine, trans-hydroxyproline, methionine, and histidine concentrations and highest (P < 0.01) lysine and citrulline concentrations among the Diet groups. Butyric acid, concentration was higher (P < 0.05) in the SER group compared to BG group. Eight medium- and long-chained acylcarnitines were higher (P < 0.05) in the BG-DW group than SER or BG groups. In general, amino acid levels decreased and acylcarnitine increased with Time (P < 0.05) in all groups. Sericea diet can be beneficial in enhancing stress coping abilities in goats due to elevated butyrate, lysine, and citrulline levels; however, SER resulted in lower energy level in goats compared to BG or BG-DW groups. Fatty acid metabolism is the main energy pathway in all groups during prolonged stress. Inclusion of certain varieties of SL in the diet must be carefully controlled to prevent possible negative effect

RNA-Seq exploration of the influence of stress on meat quality in Spanish goats

Abstract Studies exploring the transcriptome of stress and its effects on meat quality are very limited, particularly in goats. Fifty-four male Spanish goats (8-mo old; BW = 29.7 ± 2.03 kg) were randomly subjected to one of three treatments (TRT; n = 18 goats/treatment): (1) transported for 180 min, (2) transported for 30 min, or (3) held in pens (control) to analyze the transcriptome of stress and meat quality in goats using RNA-seq technology. Blood samples were collected before and after treatment, and meat samples were collected after humane slaughter for stress hormone, meat quality (Longissimus dorsi), and transcriptomic analysis. Plasma epinephrine concentrations were higher (P < 0.01) in 180 min and 30 min groups compared to the control group; however, norepinephrine concentrations were not affected by the treatment. Muscle glycogen concentrations (15 min postmortem) were lower (P < 0.01) in both 30 min and 180 min groups compared to the control group. Calpastatin levels were higher (P < 0.01) in 180 min and 30 min groups than the control group. Warner–Bratzler shear force values of loin chops were the highest in the 180 min group (4 ± 0.15, kg), lowest in the control group (3.51 ± 0.10, kg), and intermediate in the 30 min group (3.78 ± 0.09, kg; P < 0.01) both at day 1 and day 6 aging time. Additionally, desmin levels of day 6 samples were lowest in the control group, highest in 180 min group, and intermediate in 30 min group (P < 0.05). RNA-seq results showed that a total of 10,633 genes were differentially expressed (5194 up regulated; 5439 down regulated) among all comparisons (blood and day 1 and day 6 muscle samples). Among these differentially expressed genes (DEGs), KLF9, AMPK, FOXO3, PTX3, GADD45, PTPN1, CASP7, MAPK4, HSPA12A, and JAK-STAT were probably associated with the effects of stress on skeletal muscle proteins and involved in biological process such as cellular response to corticosteroid stimulus, endoplasmic reticulum stress, insulin resistance, DNA repair, apoptosis, MAPK cascade and regulation of proteolysis. The KEGG analysis revealed that AMPK and JAK-SAT signaling pathways and autophagy were among the top 20 enriched pathways in our treatment comparisons. The results provide an understanding of the genes and pathways involved in stress responses and related changes in postmortem muscle metabolism and meat quality characteristics in goats

Differential gene expression analysis using RNA-seq in the blood of goats exposed to transportation stress

Abstract Transportation stress causes significant changes in physiological responses in goats; however, studies exploring the transcriptome of stress are very limited. The objective of this study was to determine the differential gene expressions and related pathways in the blood samples using RNA-seq procedure in Spanish goats subjected to different durations of transportation stress. Fifty-four male Spanish goats (8-mo old; BW = 29.7 ± 2.03 kg) were randomly subjected to one of three treatments (TRT; n = 18 goats/treatment): (1) transported for 180 min, (2) transported for 30 min, or (3) held in pens (control). Blood samples were collected before and after treatment for stress hormone, metabolite, and transcriptomic analysis. RNA-seq technology was used to obtain the transcriptome profiles of blood. Analysis of physiological data using SAS showed that plasma cortisol concentrations were higher (P < 0.01) in 180 min and 30 min groups compared to the control group. Enrichment analysis of DEGs related to transportation stress through Gene Ontology and KEGG databases revealed that the differentially expressed genes related to inflammatory pathways, caspases, and apoptosis such as IL1R2, CASP14, CD14, TLR4, and MAPK14 were highly enriched in the transported group of goats compared to non-transported goats. Stress in goats leads to a sequence of events at cellular and molecular levels that causes inflammation and apoptosis

Influence of Excitability Rate on Physiological Responses to Stress in Goats

This study was conducted to determine if excitability score (ES) in goats can influence their physiological responses when subjected to stress. Thirty-six intact male Spanish goats (8-mo-old) were individually weighed and scored for excitability: 1 for calm (13 goats), 2 for moderately excitable (11 goats), and 3 for highly excitable (12 goats). To impose stress, goats were assigned to one of three treatments (TRT) for 90 min: (i) isolation in an open pen with metal grill panels, (ii) isolation in a pen with side panels covered using tarp sheets, and (iii) no isolation (control). Blood samples were collected at 0, 30, 60, and 90 min of isolation and physiological data were analyzed using MIXED procedures in SAS. The data from the two isolation treatments were pooled and compared with that of the control group. Plasma cortisol and non-esterified fatty acid concentrations were the lowest in goats with ES 1 (p p < 0.01). Application of full quadratic model using response surface methodology (PROC RSREG) in SAS revealed that the influence of ES on physiological stress responses over time was not the same between the TRT groups. The results indicate that physiological stress responses are greater in goats with an excitable temperament compared to goats with a calm temperament

Habituation to Livestock Trailer and Its Influence on Stress Responses during Transportation in Goats

This experiment was conducted to determine the effects of habituation to livestock trailers on stress responses in goats transported for long periods. Intact male Spanish goats (12-month old; BW = 31.6 ± 0.34 kg; N = 168) were separated into two treatment (TRT) groups and maintained on two different paddocks. Concentrate supplement was fed to one group inside two livestock trailers (5.0 × 2.3 m each; habituated group, H), while the other group received the concentrate supplement, but not inside the trailers (non-habituated, NH). After 4 weeks of habituation period, goats were subjected to a 10-h transportation stress in four replicates (n = 21 goats/replicate/TRT). Blood samples were collected by a trained individual by jugular venipuncture into vacutainer tubes before loading (Preload), 20 min after loading (0 h), and at 2-h intervals thereafter (Time) for analysis of stress responses. There was a tendency for a TRT effect (p p p < 0.05) with transportation time; however, TRT × Time interaction effects were not significant. Habituation to trailers may be beneficial in mood and energy stabilization in goats during long-distance transportation