Predikin and PredikinDB: a computational framework for the prediction of protein kinase peptide specificity and an associated database of phosphorylation sites

Background: We have previously described an approach to predicting the substrate specificity of serine-threonine protein kinases. The method, named Predikin, identifies key conserved substrate-determining residues in the kinase catalytic domain that contact the substrate in the region of the phosphorylation site and so determine the sequence surrounding the phosphorylation site. Predikin was implemented originally as a web application written in Javascript

Feeding Value of Diets for Growing-Finishing Pigs with Varying Concentrations of Corn Distillers Dried Grain with Solubles (DDGS)

Two-hundred and forty pigs (61.73 lb) were used in a 16-week study conducted to evaluate the feeding value of diets with varying concentrations of distillers dried grains with solubles (DDGS) for growing-finishing pigs. Pigs were assigned to one of four dietary treatments. Treatments consisted of a standard diet formulated on a standardized ileal digestible lysine (SID lys) basis in which a portion of dietary corn and soybean meal were replaced to include 0,5, 10 or 15% of DDGS in a 4-phase feeding regime. Treatment did not affect average daily gain (ADG), average daily feed intake (ADFI) or gain/feed (G:F) during the Grower 1, Grower 2, Finisher 1, and Finisher 2 feeding periods ( P \u3e 0.10). Overall, no linear or quadratic effects in ADG and ADFI were recorded as dietary DDGS increased (P \u3e 0.10). At day 21 and 42 backfat JBF) linearly decreased as dietary DDGS concentration increased (P = 0.008 and 0.018, respectively). A linear reduction in longissimus muscle area was recorded on day 42 JP = 0.025). Overall, growth performance was not affected by dietary DDGS inclusion increasing from 0 to 15%. The results of this study suggest that DDGS inclusion up to 15% in diets for growing-finishing pigs formulated on a SID lys basis does not affect optimum growth performance

Effects of Distillers Dried Grains with Solubles (DDGS) and paylean Supplementation on Growth Performance of Growing-finishing Pigs

Forty pigs were used in a 14-week, +phase regime study conducted to evaluate the feeding value of diets with varying concentrations of DDGS for growing-finishing pig formulated on a standardized ileal digestibility (SID) lysine (lys) basis, DDGS withdrawal at the last feeding phase, and ractopamine (RAC) supplementation four weeks prior harvesting. Treatments consisted in 0, 15 or 40% dietary DDGS inclusion supplemented or not with RAC (4.5 ppm) four weeks prior harvesting. Increased dietary DDGS inclusion resulted in a linear reduction in average daily gain (ADG) during the Grower 1 period (P = 0.002). There were no treatment effects (P \u3e 0.05) of increasing dietary DDGS inclusion for any of the variables examined during the Grower 2 feeding period. No differences among treatments were detected throughout the feeding phase Finisher 1 for ADG, average daily feed intake (ADFI), longissimus muscle area (LMA) and gain:feed (G:F) (P \u3e 0.05). During the Finisher 2 feeding phase, there were no differences among treatments due to dietary DDGS inclusion on any of the variables studied. The inclusion of RAC four weeks prior harvesting did not affect growth performance (ADG, ADFI, and G:F; P = 0.436, 0.21 7, 0.880 respectively); however, there was a numerical increase in ADG due to RAC inclusion. The examination of 98-day BF and LMA data did not show differences due to RAC inclusion (P = 0.319 and 0.728 respectively). There were no changes in growth performance or ultrasound measurements due to withdrawal of DDGS (P \u3e 0.05). Overall, growth performance was maintained as dietary DDGS inclusion increased from 0 to 40%

Production Through Four Parities of Prolific Females Developed With and Without Energy Restriction

This experiment evaluated the effects of developing gilts with ad libitum access to feed to breeding age (226 days) or feed intake restriction from 123 to 226 days of age. Gilts were managed in groups of 10 per pen. Those in the restricted group were fed two meals per day so that energy intake was 75% of that of the ad libitum group. Protein, vitamins , and minerals in their diet were increased so that daily intake of these nutrients was not restricted. A total of 661 gilts of two genetic lines that differed in reproductive rate and in lean growth rate started the experiment at 60 days of age, and one-half of the gilts of each line were developed with each feeding regimen. Growth and backfat were recorded at 14-day intervals from 60 to 226 days of age. Boar exposure to determine age at puberty was initiated at 140 days of age. A total of 509 gilts that could be mated at second or later post-pubertal estrus were designated as breeders and their production through four parities was recorded. Females were managed alike after 230 days of age and were culled only for reproductive failure, death, ruptures, or severe foot and leg problems. No interactions of genetic line by treatment were significant as females of both lines responded similarly to the developmental regimens. Developing gilts with energy restriction significantly decreased the proportion of gilts that expressed a pubertal estrus by 230 days of age, from 96% to 86% and increased their age at puberty from 174.1 to 177.5 days. Thereafter, females developed with both regimens had similar reproductive performance. Measures of productivity through parity 4 were 8 to 11% greater for females developed with energy restriction, but none of the differences were significant (P ≥ 0.14)

Nutrition During Gilt Development and Genetic Line Affect Reproductive Rate Through Parity 1

Effects of allowing gilts ad libitum access to feed until breeding age or developing them with 25% energy restriction from 123 days of age to breeding on reproductive success through parity I were studied with a total of 639 gilts of two lines that differ in lean growth and reproduction. Gilts of the two lines had common sires, an industry maternal line, but dams were from different populations. One line of gilts, LW x LR, represented standard industry Large White x Landrace cross females. The other gilts, L45X, were daughters of Nebraska selection Line 45 that has been selected 27generations for increased litter size with additional selection for increased growth and decreased fat in the last seven generations. More L45X than LW x LR gilts (95 vs. 88%, P \u3c 0.01) and more gilts developed with ad libitum intake than with restricted intake (96 vs. 86%, P \u3c 0.01) expressed puberty by 226 days of age. For gilts that expressed puberty, mean age at puberty was 6 days less (P \u3c 0.01) for L45X than LWx LR gilts, but did not differ between gilts on the two developmental regimens. For all gilts, the likelihood of expressing puberty increased with increasing weight at 123 days of age. It was also greater for gilts that attained heavier weights with greater backfat at 226 days of age, but the efiect varied among lines and gilt developmental regimens. Increasing weight and backfat at 226 days of age increased the likelihood of producing a parity 1 litter for L45Xgilts developed with restricted feeding, but not for other groups. Number of live born pigs per litter was affected by line, being greater for L45X gilts (P \u3c 0.05), but not by gilt developmental regimen. Neither line nor gilt developmental regimen affected maternal ability as measured by number and weight of pigs weaned. A 25% energy restriction duringgilt development decreases the likelihood that gilts express estrus by 226 days of age, but has little effect on subsequent reproductive performance

Effects of Nutrition During Gilt Development and Genetic Line on Farrowing Rates Through Parity 3, Causes of Culling, Sow Weights and Backfats through Parity 4, and Factors Affecting Farrowing Rates

Gilts of two genetic lines were developed with either ad libitum access to feed or energy restriction (75% of ad libitum) to determine effects on subsequent sow performance and longevity. Gilts can be developed with regimens in which energy is restricted during the growing period but the proportion that express pubertal estrus may be reduced in leaner, faster growing lines. Effects on subsequent farrowing rates are small. Sow weight and buckfat at farrowing and weaning of Parity 1 litters affect the likelihood of producing a Parity 2 litter, but these effects are dependent on lean growth rate of the line and on the gilt development regimen. Weight was important in the slower growing, fatter line developed with the restricted feeding regimen; backfat was important in the leaner, faster growing line, but the effect was twice as great in females developed with restricted feeding than for those developed with ad libitum access to feed

Cross-reactive Antibody Response to mRNA SARS-CoV-2 Vaccine After Recent COVID-19-Specific Monoclonal Antibody Therapy.

The efficacy of coronavirus disease 2019 (COVID-19) vaccines administered after COVID-19-specific monoclonal antibody is unknown, and "antibody interference" might hinder immune responses leading to vaccine failure. In an institutional review board-approved prospective study, we found that an individual who received mRNA COVID-19 vaccination <40 days after COVID-19-specific monoclonal antibody therapy for symptomatic COVID-19 had similar postvaccine antibody responses to SARS-CoV-2 receptor binding domain (RBD) for 4 important SARS-CoV-2 variants (B.1, B.1.1.7, B.1.351, and P.1) as other participants who were also vaccinated following COVID-19. Vaccination against COVID-19 shortly after COVID-19-specific monoclonal antibody can boost and expand antibody protection, questioning the need to delay vaccination in this setting.Trial registrationThe St. Jude Tracking of Viral and Host Factors Associated with COVID-19 study; NCT04362995; https://clinicaltrials.gov/ct2/show/NCT04362995

Host Predictors of Broadly Cross-Reactive Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern Differ Between Infection and Vaccination.

BACKGROUND: Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination there is significant variability between individuals in protective antibody levels against SARS-CoV-2, and within individuals against different virus variants. However, host demographic or clinical characteristics that predict variability in cross-reactive antibody levels are not well-described. These data could inform clinicians, researchers, and policymakers on the populations most likely to require vaccine booster shots. METHODS: In an institutional review board-approved prospective observational cohort study of staff at St. Jude Childrens Research Hospital, we identified participants with plasma samples collected after SARS-CoV-2 infection, after mRNA vaccination, and after vaccination following infection, and quantitated immunoglobulin G (IgG) levels by enzyme-linked immunosorbent assay to the spike receptor binding domain (RBD) from 5 important SARS-CoV-2 variants (Wuhan Hu-1, B.1.1.7, B.1.351, P.1, and B.1.617.2). We used regression models to identify factors that contributed to cross-reactive IgG against 1 or multiple viral variants. RESULTS: Following infection, a minority of the cohort generated cross-reactive antibodies, IgG antibodies that bound all tested variants. Those who did had increased disease severity, poor metabolic health, and were of a particular ancestry. Vaccination increased the levels of cross-reactive IgG levels in all populations, including immunocompromised, elderly, and persons with poor metabolic health. Younger people with a healthy weight mounted the highest responses. CONCLUSIONS: Our findings provide important new information on individual antibody responses to infection/vaccination that could inform clinicians on populations that may require follow-on immunization

SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cells.

Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection. Exposure order determined the distribution between spike-specific and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7-CD45RA+ effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell antigen receptor (TCR) sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory