Serosurvey of human antibodies recognizing Aedes aegypti D7 salivary proteins in Colombia

Citation: Londono-Renteria, B. L., Shakeri, H., Rozo-Lopez, P., Conway, M. J., Duggan, N., Jaberi-Douraki, M., & Colpitts, T. M. (2018). Serosurvey of Human Antibodies Recognizing Aedes aegypti D7 Salivary Proteins in Colombia. Frontiers in Public Health, 6. https://doi.org/10.3389/fpubh.2018.00111Background: Dengue is one of the most geographically significant mosquito-borne viral diseases transmitted by Aedes mosquitoes. During blood feeding, the mosquito deposits salivary proteins that induce antibody responses. These can be related to the intensity of exposure to bites. Some mosquito salivary proteins, such as D7 proteins, are known as potent allergens. The antibody response to D7 proteins can be used as a marker to evaluate the risk of exposure and disease transmission, and provide critical information for understanding the dynamics of vector-host interactions. Methods: The study was conducted at the Los Patios Hospital, Cucuta, Norte de Santander, Colombia. A total of 63 participants were enrolled in the study. Participants were categorized into three disease status groups, age groups, and socioeconomic strata. The level of IgG antibodies against D7 Aedes proteins was determined by ELISA. We used a statistical approach to determine if there is an association between antibody levels and factors such as age, living conditions, and dengue virus infection. Results: We found that IgG antibodies against D7 proteins were higher in non-DENV infected individuals in comparison to DENV-infected participants. Also, age factor showed a significant positive correlation with IgG antibodies against D7 proteins, and the living conditions (socioeconomic stratification), in people ages 20 years or older, are a statistically significant factor in the variability of IgG antibodies against D7 proteins. Conclusions: This pilot study represents the first approximation to elucidate any correlation between the antibody response against mosquito D7 salivary proteins and its correlation with age, living conditions and dengue virus infection in a dengue endemic area

Development of a subcutaneous ear implant to deliver an anaplasmosis vaccine to dairy steers

Bovine anaplasmosis is the most prevalent tick-transmitted disease of cattle worldwide and a major obstacle to profitable beef production. Use of chlortetracycline-medicated feed to control active anaplasmosis infections during the vector season has raised concerns about the potential emergence of antimicrobial resistance in bacteria that may pose a risk to human health. Furthermore, the absence of effectiveness data for a commercially available, conditionally licensed anaplasmosis vaccine is a major impediment to implementing anaplasmosis control programs. The primary objective of this study was to develop a single-dose vaccine delivery platform to produce long-lasting protective immunity against anaplasmosis infections. Twelve Holstein steers, aged 11-12 weeks, were administered a novel 3-stage, single-dose vaccine against Anaplasma marginale (Am) major surface protein 1a. The vaccine consisted of a soluble vaccine administered subcutaneously (s.c.) for immune priming, a vaccine depot of a biodegradable polyanhydride rod with intermediate slow release of the vaccine for boosting immune response, and an immune-isolated vaccine platform for extended antigen release (VPEAR implant) deposited s.c. in the ear. Six calves were randomly assigned to two vaccine constructs (n=3) that featured rods and implants containing a combination of two different adjuvants, diethylaminoethyl (DEAE)-Dextran and Quil-A (Group A). The remaining 6 calves were randomly assigned to two vaccine constructs (n=3) that featured rods and implants containing the same adjuvant (either DEAE-Dextran or Quil A) (Group B). Twenty one months post-implantation, calves were challenged intravenously with Am stabilate and were monitored weekly for signs of fever, decreased packed cell volume (PCV) and bacteremia. Data were analyzed using a mixed effects model and chi-squared tests (SAS v9.04.01, SAS Institute, Cary, NC). Calves in Group A had higher PCV than calves in Group B (P = 0.006) at day 35 post-infection. Calves in Group A were less likely to require antibiotic intervention compared with calves in Group B (P = 0.014). Results indicate that calves exhibited diminished clinical signs of anaplasmosis when antigen was delivered with a combination of adjuvants as opposed to a single adjuvant. This demonstrates the feasibility of providing long lasting protection against clinical bovine anaplasmosis infections using a subcutaneous ear implant vaccine construct

Evaluation of Precision Livestock Technology and Human Scoring of Nursery Pigs in a Controlled Immune Challenge Experiment

The objectives were to determine the sensitivity, specificity, and cutoff values of a visual-based precision livestock technology (NUtrack), and determine the sensitivity and specificity of sickness score data collected with the live observation by trained human observers. At weaning, pigs (n = 192; gilts and barrows) were randomly assigned to one of twelve pens (16/pen) and treatments were randomly assigned to pens. Sham-pen pigs all received subcutaneous saline (3 mL). For LPS-pen pigs, all pigs received subcutaneous lipopolysaccharide (LPS; 300 µg/kg BW; E. coli O111:B4; in 3 mL of saline). For the last treatment, eight pigs were randomly assigned to receive LPS, and the other eight were sham (same methods as above; half-and-half pens). Human data from the day of the challenge presented high true positive and low false positive rates (88.5% sensitivity; 85.4% specificity; 0.871 Area Under Curve, AUC), however, these values declined when half-and-half pigs were scored (75% sensitivity; 65.5% specificity; 0.703 AUC). Precision technology measures had excellent AUC, sensitivity, and specificity for the first 72 h after treatment and AUC values were \u3e0.970, regardless of pen treatment. These results indicate that precision technology has a greater potential for identifying pigs during a natural infectious disease event than trained professionals using timepoint sampling

Identifying a Milk-Replacer and Weaning Strategy for Holstein Calves Using Automated Behavioral Measures of Lying and Environmental Enrichment Device Use

In dairy production, “weaning readiness” is often based on solid feed intake. The goal of this study was to determine weaning readiness using feed-intake, lying-behaviors, and the use of an environmental enrichment device (EED) in calves that underwent 1 of 4 milk-replacer and weaning protocols. Twenty-eight male Holstein calves (95 ± 2.6 lb BW at 1 d of age) were housed in individual pens and initially fed one type of milk replacer (25% crude protein (CP), 17% fat, 1.45 lb of dry matter (DM)) via nipplebuckets twice a day (AM and PM), and one type of textured calf starter (ad libitum; 20% CP and 37% starch). At age 3 days, calves were randomly assigned to one of the four nutrition-weaning strategies:1. MOD-STEP - 1.46 lb per day of milk replacer; 2-step weaned, initiated at age 6 weeks, completed 3 days later; 2. HI-STEP - 2.4 lb per day of milk replacer; 2-step weaned, initiated at age 5 weeks and completed 1 week later; 3. HI-LATE - 2.4 lb per day of milk replacer; 2-step weaned, initiated at age 7 weeks and completed 1 week later; and 4. HI-GRAD - 2.4 lb per day of milk replacer; 5-step weaned, initiated at age 6 week and completed 2 weeks later. Each calf’s pen had an EED, which included a dummy-nipple attached to a bottle and holder. A sensor and automated logger tracked each event (1 Hz) that the calf manipulated the EED (25 Hz sensitivity). Each calf was fitted with an accelerometer on the back leg to automatically measure lying behaviors. The device collected the y-axis (lie vs. stand) and z-axis (right or left percent during lying) of the calf every minute. For this experiment, 3-day sample periods were analyzed before and after weaning was initiated. In addition, the 3 days following weaning-completion were sampled. Feed intake among MOD-STEP calves increased by 1.0 ± 0.19 lb after the first bottle was removed (P ≤ 0.05), and then by 1.5 ± 0.19 SE lb after completion of weaning (P ≤ 0.05). The use of EED did not change among MOD-STEP calves (P \u3e 0.05), but after weaning, they increased their lying time, especially on their left side (P ≤ 0.05). These changes in lying-behaviors may indicate increased comfort and maturity of the rumen. On the contrary, calves in the HI-STEP treatment ate the least amount of feed overall (P \u3c 0.05), and they used the EED the most (P \u3e 0.05). Calves in the HI-STEP treatment showed reduced lying bouts after weaning (P ≤ 0.05), but no other lying-measures changed (P \u3e 0.05). The HI-LATE calves had similar feed intake and EED use compared to MOD-STEP calves. These findings suggest that weaning age needs to be more than 8 weeks for calves fed 2.4 lb of milk replacer per day. Gradual weaning may also improve feed intake and reduce EED use. When calves were gradually weaned starting at age 6 weeks and completed at age 8 weeks, they had the same amount of solid feed intake as HI-LATE calves. More research is needed to determine if increased feed intake and reduced EED use are also indicators that cross-sucking is less likely to occur when calves are grouped after weaning

Autoimmune responses in T1DM : quantitative methods to understand onset, progression, and prevention of disease

Understanding the physiological processes that underlie autoimmune disorders and identifying biomarkers to predict their onset are two pressing issues that need to be thoroughly sorted out by careful thought when analyzing these diseases. Type 1 diabetes ( T1D ) is a typical example of such diseases. It is mediated by autoreactive cytotoxic CD4 + and CD8 + T‐cells that infiltrate the pancreatic islets of Langerhans and destroy insulin‐secreting β‐cells, leading to abnormal levels of glucose in affected individuals. The disease is also associated with a series of islet‐specific autoantibodies that appear in high‐risk subjects ( HRS ) several years prior to the onset of diabetes‐related symptoms. It has been suggested that T1D is relapsing‐remitting in nature and that islet‐specific autoantibodies released by lymphocytic B‐cells are detectable at different stages of the disease, depending on their binding affinity (the higher, the earlier they appear). The multifaceted nature of this disease and its intrinsic complexity make this disease very difficult to analyze experimentally as a whole. The use of quantitative methods, in the form of mathematical models and computational tools, to examine the disease has been a very powerful tool in providing predictions and insights about the underlying mechanism(s) regulating its onset and development. Furthermore, the models developed may have prognostic implications by aiding in the enrollment of HRS into trials for T1D prevention. In this review, we summarize recent advances made in determining T‐ and B‐cell involvement in T1D using these quantitative approaches and delineate areas where mathematical modeling can make further contributions in unraveling certain aspect of this disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106988/1/pedi12148.pd

Predicting the Prognostic Value of <i>POLI</i> Expression in Different Cancers via a Machine Learning Approach

Translesion synthesis (TLS) is a cell signaling pathway that facilitates the tolerance of replication stress. Increased TLS activity, the particularly elevated expression of TLS polymerases, has been linked to resistance to cancer chemotherapeutics and significantly altered patient outcomes. Building upon current knowledge, we found that the expression of one of these TLS polymerases (POLI) is associated with significant differences in cervical and pancreatic cancer survival. These data led us to hypothesize that POLI expression is associated with cancer survival more broadly. However, when cancers were grouped cancer type, POLI expression did not have a significant prognostic value. We presented a binary cancer random forest classifier using 396 genes that influence the prognostic characteristics of POLI in cervical and pancreatic cancer selected via graphical least absolute shrinkage and selection operator. The classifier was then used to cluster patients with bladder, breast, colorectal, head and neck, liver, lung, ovary, melanoma, stomach, and uterus cancer when high POLI expression was associated with worsened survival (Group I) or with improved survival (Group II). This approach allowed us to identify cancers where POLI expression is a significant prognostic factor for survival (p = 0.028 in Group I and p = 0.0059 in Group II). Multiple independent validation approaches, including the gene ontology enrichment analysis and visualization tool and network visualization support the classification scheme. The functions of the selected genes involving mitochondrial translational elongation, Wnt signaling pathway, and tumor necrosis factor-mediated signaling pathway support their association with TLS and replication stress. Our multidisciplinary approach provides a novel way of identifying tumors where increased TLS polymerase expression is associated with significant differences in cancer survival

Dependence of T-cell waves, caused by the transience of the autoimmune state , on T-cell avidity and killing efficacy.

<p>The duration of T-cell waves for are plotted as a function of the parametric quantity , representing T-cell avidity, at the following values of T-cell killing efficacies : (solid line), (dashed line), (dotted line) and (dashed-dotted line) (day cell)⁻¹. These curves are all steadily decreasing functions of and vanish at (.</p