Variation In Specificity Research Articles

Differential survival and dispersal of avian feather mites with contrasting host specificities

Abstract Host specificity is a fundamental life history trait of symbionts and exists on a broad continuum from symbionts that are specific to one or a few hosts (host specialists), to those associated with multiple different host species (host generalists). However, the biological mechanisms underlying the complexity and wide variation in symbiont host specificity are poorly understood from both the symbiont and host perspectives across many symbiotic systems. Feather mites are common avian symbionts that vary in their host specificity from extreme host generalists to host specialists, even among species within the same genus. Here, we measured and compared survival probability and rate of dispersal to determine how these traits differ between two species of feather mites in the same genus: one host generalist associated with 17 host species (Amerodectes ischyros) and one host specialist with only one known host (A. protonotaria). We initially predicted that the host generalist would live longer and disperse more rapidly but discovered that while the host generalist mite survived longer, the host specialist mite dispersed more quickly. The differing environmental and ecological conditions in which the hosts of these mites are associated may explain the survival and dispersal patterns we uncovered, as differential microclimates may have led to different selective pressures on each species of mite. We also noted mite behavioural observations and suggest experiments to extend our understanding of feather mite ecology and evolution.

Epidemiology of Q-fever in domestic ruminants and humans in Africa. A systematic review

Abstract Q-fever is a zoonotic infectious disease caused by the gram-negative, intracellular, spore-forming bacterium Coxiella burnetii . Infected ruminants (cattle, sheep, and goats) are the reservoirs of the pathogen and thus an important source of infection in humans. This systematic review aims to consolidate the knowledge and awareness of Q-fever in Africa and identify future research opportunities and possible interventions in low-resource settings. We review information on Q-fever epidemiology and the diagnostic challenges in humans and domestic ruminants in Africa from the last 23 years. Six databases including university repositories were searched for relevant articles. A total of 84 studies and 4 theses met the selection criteria and were thus included in the review. They include serological and molecular studies of Q-fever in humans or domestic ruminants in 24/54 African countries. The mean seroprevalence estimates were 16% (95%CI 11–23%) in humans; 14% (95%CI 10–20%) in cattle; 13% (95%CI 9–18%) in sheep; and 21% (95%CI 15–29%) in goats. The mean prevalence for molecular detection of the pathogen were 3% (95%CI 0–16%) in humans; 9% (95%CI 4–19%) in cattle; 16% (95%CI 5–41%) in sheep; and 23% (95%CI 20–80%) in goats. The number of studies that identified risk factors for exposure among domestic ruminants was: sex (n = 6), age (n = 17), contact with other animals (n = 5), lack of quarantine of newly purchased animals (n = 1), extensive grazing system (n = 4), herd size (2), history of abortion (n = 5), absence of vaccination (n = 2), and high temperature (n = 1). The number of studies that reported protective factors was: sanitation (n = 2), burying and/ or burning the aborted foetus (n = 2), and young (age) (n = 2). The studies that identified risk factors for human disease infection included: close contact to animals (n = 7), age (n = 3), and gender (n = 5), while those identifying protective factors included: living in non-irrigated areas (n = 1), awareness/knowledge about zoonosis (n = 1), rodent control (n = 1), sanitation/disinfection of equipment after and before use (n = 1), occasional grazing (n = 1), and do nothing to aborted materials (n = 1). Diagnostic challenges such as poverty, lack of a well-equipped laboratory with biosafety level 3 specific for Q-fever testing, unspecific and self-limiting clinical signs/symptoms, lack of gold standard test, and variation in test specificity and sensitivity were identified. The disease is likely to be widespread in Africa and of public importance and underreported thus ‘One Health’ approaches to future studies are recommended. Further studies should focus on concurrent studies of human and livestock populations. One Health Impact Statement This review applies to One Health stakeholders including, the public, players in the livestock value chain, animal/ human/ environmental health workers, policy makers, and other implementers. This review summarizes the available information regarding Q-fever ( Coxiella burnetii ) in animals and humans in Africa, providing new information on the magnitude of the disease, and risk factors for infection. This information highlights the need for collaboration among One Health stakeholders and multisectoral cooperation towards achieving the One Health goals. The sharing of knowledge generated through research from academic, non-academic, and local/ indigenous knowledge will allow a new foundation for disease control that is applicable and beneficial to all stakeholders under the One Health umbrella rather than academic scientists alone.

Reliability of Genetic Alterations in Predicting Ceftriaxone Resistance in Neisseria gonorrhoeae Globally.

ABSTRACTAntimicrobial resistance in N. gonorrhoeae is increasing globally, and ceftriaxone is the recommended treatment for empirical therapy in most settings. Developing molecular assays to detect decreased ceftriaxone susceptibility is critical. Using PathogenWatch, a public database of N. gonorrhoeae genomes, antibiotic susceptibility data and DNA sequences of different genes associated with ceftriaxone resistance were extracted. That information was used to determine the sensitivity and specificity of different molecular markers and algorithms to predict decreased susceptibility to ceftriaxone. A total of 12,943 N. gonorrhoeae genomes were extracted from the PathogenWatch database, of which 9,540 genomes were used in the analysis. The sensitivity and specificity of specific molecular markers and algorithms were largely consistent with prior reports. Small variation (<10%) in either sensitivity or specificity occurred. Certain algorithms using different molecular markers at various prevalence of decreased ceftriaxone susceptibility identified a potentially clinically useful range of positive and negative predictive values. We validated previously described mutations and algorithms in a large public database containing a global collection of N. gonorrhoeae genomes. Certain mutations and algorithms resulted in sensitivity and specificity values consistent with those of prior studies. Further research is needed to integrate these markers and algorithms into the development of molecular assays to predict decreased ceftriaxone susceptibility.IMPORTANCE Antimicrobial resistance in Neisseria gonorrhoeae (N. gonorrhoeae), the causative agent of gonorrhea, is rising globally. Ceftriaxone is the last remaining antibiotic for empirical treatment of gonorrhea. Developing molecular tests to predict ceftriaxone resistance can help to improve detection and surveillance of ceftriaxone resistance. Here, we utilized PathogenWatch, a public global online database of N. gonorrhoeae genomes, to evaluate different genetic markers in predicting decreased susceptibility to ceftriaxone. We compiled MICs for ceftriaxone from the PathogenWatch database and used a computational approach to extract all the genetic markers from the genomic data. We determined the sensitivity and specificity for predicting decreased ceftriaxone susceptibility among several combinations of genetic markers. We identified several combinations of genetic markers with high predictive values for decreased susceptibility to ceftriaxone. These combinations of genetic markers might be promising candidates for future molecular tests to predict ceftriaxone resistance.

Symptom- and chest-radiography screening for active pulmonary tuberculosis in HIV-negative adults and adults with unknown HIV status.

Symptom- and chest-radiography screening for active pulmonary tuberculosis in HIV-negative adults and adults with unknown HIV status.

Acupoint Selection for Autonomous Massage Based on Infrared Thermography

After breast cancer surgery, the patient has difficulty in selecting the acupoints for autonomous massage, due to the changes in muscles and nerves on the affected side. To overcome the difficulty, this paper proposes an acupoint selection method for autonomous massage after breast cancer surgery, based on infrared thermography. Firstly, the contrast of the infrared thermogram was enhanced by image differencing, and the chest region and upper limbs were segmented through global thresholding. Next, temperature specific detection and edge detection algorithms were combined to automatically locate the main chest organs, and the horizontal and vertical axes of the upper limbs, according to the temperature specificity and temperature variation induced by the physiological structure of chest and upper limbs. Furthermore, the main acupoints for autonomous massage were determined, based on their positions relative to the axes of main organs. Experimental results show that our method achieved a positioning accuracy greater than 90.12%. The excellent positioning effect improves the compliance of patients in active rehabilitation.

The binding specificity of bZIP/DNA from a knob-socket analysis

The basic leucine zipper motif (bZIP) is a simple DNA-binding domain recognizing consensus sequences through interactions between α-helices and DNA. This α-helical domain consists of an N-terminal DNA-binding basic and C-terminal leucine zipper region forming a coiled-coil. As a transcription factor, bZIPs exhibit a high degree of variance in the DNA binding region. This study applies a knob-socket analysis to characterize the multibody determinants of the variation in specificity between individual bZIP monomers and their respective four-base half-site.

Assessing the EULAR/ACR classification criteria for patients with systemic lupus erythematosus

ABSTRACT Introduction The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) established a new criteria system with antinuclear antibodies (ANA) as an entry criterion, domains, and weighted criteria. In the validation cohort, specificity and sensitivity each matched the best performance of the previous criteria sets. Areas covered Groups worldwide have externally validated the EULAR/ACR SLE classification criteria. Studies on the classification criteria were searched on PubMed and analyzed for their estimates of criteria performance. These were combined with new insights from the EULAR/ACR criteria project to understand any differences in assessments. Expert opinion Overall, external validation supports the concepts and performance of the new SLE criteria. Variation in specificity in part appears to be related to incomplete application of the attribution rule of the criteria, under which items should only be counted for SLE if there were no more likely alternative explanation. Scientific uncertainty, and a lack of worldwide consensus, on the borderline between disease entities, e.g. between SLE and isolated cutaneous lupus erythematosus (CLE), also affected variation in estimates. For sensitivity, the performance of tests for ANA is critical.

Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy Discriminates the Elderly with a Low and High Percentage of Pathogenic CD4+ T Cells.

In the aging process, the presence of interleukin (IL)-17-producing CD4+CD28-NKG2D+T cells (called pathogenic CD4+ T cells) is strongly associated with inflammation and the development of various diseases. Thus, their presence needs to be monitored. The emergence of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy empowered with machine learning is a breakthrough in the field of medical diagnostics. This study aimed to discriminate between the elderly with a low percentage (LP; ≤3%) and a high percentage (HP; ≥6%) of pathogenic CD4+CD28-NKG2D+IL17+ T cells by utilizing ATR-FTIR coupled with machine learning algorithms. ATR spectra of serum, exosome, and HDL from both groups were explored in this study. Only exosome spectra in the 1700–1500 cm−1 region exhibited possible discrimination for the LP and HP groups based on principal component analysis (PCA). Furthermore, partial least square-discriminant analysis (PLS-DA) could differentiate both groups using the 1700–1500 cm−1 region of exosome ATR spectra with 64% accuracy, 69% sensitivity, and 61% specificity. To obtain better classification performance, several spectral models were then established using advanced machine learning algorithms, including J48 decision tree, support vector machine (SVM), random forest (RF), and neural network (NN). Herein, NN was considered to be the best model with an accuracy of 100%, sensitivity of 100%, and specificity of 100% using serum spectra in the region of 1800–900 cm−1. Exosome spectra in the 1700–1500 and combined 3000–2800 and 1800–900 cm−1 regions using the NN algorithm gave the same accuracy performance of 95% with a variation in sensitivity and specificity. HDL spectra with the NN algorithm also showed excellent test performance in the 1800–900 cm−1 region with 97% accuracy, 100% sensitivity, and 95% specificity. This study demonstrates that ATR-FTIR coupled with machine learning algorithms can be used to study immunosenescence. Furthermore, this approach can possibly be applied to monitor the presence of pathogenic CD4+ T cells in the elderly. Due to the limited number of samples used in this study, it is necessary to conduct a large-scale study to obtain more robust classification models and to assess the true clinical diagnostic performance.

Anti-dsDNA Testing Specificity for Systemic Lupus Erythematosus: A Systematic Review.

Autoantibody specificity in autoimmune diseases is variable due to each patient's individual spectrum of autoantibodies and the inherent differences between detection methods and tests. Since false-positive results have downstream consequences, we conducted a comprehensive assessment of anti-double stranded DNA (anti-dsDNA) specificity from published studies of systemic lupus erythematosus (SLE). A systematic review (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects) identified cross-sectional or case-control studies published January 2004 to August 2019, reporting anti-dsDNA test accuracy data in SLE. Study quality was assessed using Quality Assessment Tool for Diagnostic Accuracy Studies, version 2. A meta-analysis was conducted to estimate specificity by test method or named test where feasible. Thirty studies were included covering 43 different tests. The Crithidia luciliae indirect immunofluorescence test (CLIFT) and fluorescence enzyme immunoassay methods are likely to be ≥ 90% specific (Euroimmun 97.8% (95% CI 96.2%-98.7%) 4 studies; EliA 94.7% (95% CI 91.7%-96.7%), 6 studies; CLIFT 98.7% (95% CI 96.7%-99.5%), 8 studies/7 tests]. For other test methods, specificity was not fully demonstrated to be ≥ 90% and/or the control group included healthy patients possibly overestimating specificity. More studies are required for NOVA Lite [96.0% (95% CI 87.2%-98.9%), 5 studies], chemiluminescence immunoassays [92.3% (95% CI 83.6%-96.6%), 6 studies/4 tests], multiplex immunoassays [89.3% (95% CI 86.1%-91.8%), 4 studies/2 tests], and Farr fluorescent immunoassays (no estimate, 2 studies). Specificity data reported for Farr radioimmunoassays [93.8% (95% CI 85.4-97.5%), 11 studies, 9 tests] and enzyme-linked immunosorbent assays [93.4% (95% CI 89.9%-95.7%), 15 studies/16 tests] lacked consistency. Anti-dsDNA testing shows considerable variation in test specificity, with potential impact on the management of SLE patients. This review may help laboratory specialists and clinicians choose and interpret the appropriate anti-dsDNA test for their setting.

The diagnostic accuracy of coronary computed tomography angiography in patients with and without previous coronary interventions

BackgroundInvasive coronary angiography (ICA) is the gold standard for imaging coronary arteries and the severity of coronary artery disease (CAD). Coronary computed tomography angiography (CCTA) has undergone remarkable progress in the diagnosis of CAD. ObjectivesTo evaluate the effect of prior vs no previous coronary interventions on the diagnostic accuracy of CCTA as an alternative to ICA to improve health outcomes for patients with suspected CAD. MethodsA prospective cohort study was carried out among patients suspected of CAD and for evaluation of grafts and stents to investigate recurrent ischemic symptoms. 120 patients imaged by CCTA were then referred to ICA, which is considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CCTA were assessed relative to ICA. ResultsBased on a per-patient analysis, the comparison with ICA reveals variations in sensitivity, specificity, PPV, NPV and accuracy of CCTA. In patients without any previous coronary interventions, the sensitivity was 97.8%, and specificity was 95.6%. The PPV and NPV were 97.8% and 95.5%, respectively. Regarding patients with coronary artery bypass grafts (CABG), the sensitivity was 95% and specificity 100%. The PPV and NPV were 100% and 90.9%, respectively. Regarding patients with prior percutaneous coronary intervention (PCI), the results were a sensitivity of 84.6%, specificity of 77.8%, PPV of 84.6% and NPV of 77.8%. ConclusionCCTA is a powerful diagnostic tool, especially for the evaluation of the major coronary arteries and evaluation of patients with prior CABG. ICA is recommended for evaluation of patients with an intracoronary stent.

Monitoring plasmatic concentrations of efavirenz for prediction of clinical outcomes in people living with HIV

Objective: To assess the ability of efavirenz plasma concentrations to predict clinical outcomes. Methods: This is a cross-sectional study in people living with HIV on efavirenz antiretroviral therapy. The ROC curve (Receiver Operating Characteristic) analysis was carried out in order to verify the variation in sensitivity and specificity between the efavirenz plasma concentration and the other variables of interest in the study. The study was approved by the Human Research Ethics Committee of the University of São João del-Rei, Central-West Dona Lindu Campus, as per CAAE 41775015.3.0000.5545. Results: Among the 108 patients included in the study, the median age was 54.5 years (IQ25%: 41.0; IQ75%: 63.0). The efavirenz plasma concentration was not able to predict outcomes such as viral suppression (AUC: 0.525; CI95%: 0.334 - 0.716; p = 0.803), immune response (AUC: 0.501; CI95%: 0.390 - 0.612; p = 0.982), presence of adverse events (1 adverse event - AUC: 0.326: CI95%: 0.156 - 0.497; p = 0.103) / ≥ 4 adverse events – AUC = 0.432; CI95%: 0.323 - 0.542; p = 0.232) and adherence (AUC = 0.537; CI95%: 0.423 - 0.651; p = 0.520). Conclusions: More studies are needed to estimate the relationship between clinical outcomes and efavirenz plasma concentrations in current clinical protocols. Therefore, the accumulation of evidence on the subject is essential to identify the feasibility of therapeutic monitoring of antiretrovirals for the purpose of optimizing parameters such as efficacy, safety and adherence.

Mouse Organ-Specific Proteins and Functions

Organ-specific proteins (OSPs) possess great medical potential both in clinics and in biomedical research. Applications of them—such as alanine transaminase, aspartate transaminase, and troponins—in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human populations are well known, yet their effects on OSPs are less addressed. Here, we used mice as a model and implemented a breadth study to examine the panorgan proteome for potential variations in organ specificity in different genetic backgrounds. Using reasonable resources, we generated panorgan proteomes of four in-bred mouse strains. The results revealed a large diversity that was more profound among OSPs than among proteomes overall. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ-specific and are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.

The activation fragment of PAR2 is elevated in serum from patients with rheumatoid arthritis and reduced in response to anti-IL6R treatment

Osteoarthritis (OA) and rheumatoid arthritis (RA) are serious and painful diseases. Protease-activated receptor 2 (PAR2) is involved in the pathology of both OA and RA including roles in synovial hyperplasia, cartilage destruction, osteophyogenesis and pain. PAR2 is activated via cleavage of its N-terminus by serine proteases. In this study a competitive ELISA assay was developed targeting the 36-amino acid peptide that is cleaved and released after PAR2 activation (PRO-PAR2). Technical assay parameters including antibody specificity, intra- and inter-assay variation (CV%), linearity, accuracy, analyte stability and interference were evaluated. PRO-PAR2 release was confirmed after in vitro cleavage of PAR2 recombinant protein and treatment of human synovial explants with matriptase. Serum levels of 22 healthy individuals, 23 OA patients and 15 RA patients as well as a subset of RA patients treated with tocilizumab were evaluated. The PRO-PAR2 antibody was specific for the neo-epitope and intra-inter assay CV% were 6.4% and 5.8% respectively. In vitro cleavage and matriptase treated explants showed increased PRO-PAR2 levels compared to controls. In serum, PRO-PAR2 levels were increased in RA patients and decreased in RA patients treated with tocilizumab. In conclusion, PRO-PAR2 may be a potential biomarker for monitoring RA disease and pharmacodynamics of treatment.

Probing the functions of friedelane-type triterpene cyclases from four celastrol-producing plants.

Triterpenes are among the most diverse plant natural products, and their diversity is closely related to various triterpene skeletons catalyzed by different 2,3-oxidosqualene cyclases (OSCs). Celastrol, a friedelane-type triterpene with significant bioactivities, is specifically distributed in higher plants, such as Celastraceae species. Friedelin is an important precursor for the biosynthesis of celastrol, and it is synthesized through the cyclization of 2,3-oxidosqualene, with the highest number of rearrangements being catalyzed by friedelane-type triterpene cyclases. However, the molecular mechanisms underlying the catalysis of friedelin production by friedelane-type triterpene cyclases have not yet been fully elucidated. In this study, transcriptome data of four celastrol-producing plants from Celastraceae were used to identify a total of 21 putative OSCs. Through functional characterization, the friedelane-type triterpene cyclases were separately verified in the four plants. Analysis of the selection pressure showed that purifying selection acted on these OSCs, and the friedelane-type triterpene cyclases may undergo weaker selective restriction during evolution. Molecular docking and site-directed mutagenesis revealed that changes in some amino acids that are unique to friedelane-type triterpene cyclases may lead to variations in catalytic specificity or efficiency, thereby affecting the synthesis of friedelin. Our research explored the functional diversity of triterpene synthases from a multispecies perspective. It also provides some references for further research on the relative mechanisms of friedelin biosynthesis.

OUHP: an optimized universal hairpin primer system for cost-effective and high-throughput RT-qPCR-based quantification of microRNA (miRNA) expression.

MicroRNAs (miRNAs or miRs) are single-stranded, ∼22-nucleotide noncoding RNAs that regulate many cellular processes. While numerous miRNA quantification technologies are available, a recent analysis of 12 commercial platforms revealed high variations in reproducibility, sensitivity, accuracy, specificity and concordance within and/or between platforms. Here, we developed a universal hairpin primer (UHP) system that negates the use of miRNA-specific hairpin primers (MsHPs) for quantitative reverse transcription PCR (RT-qPCR)-based miRNA quantification. Specifically, we analyzed four UHPs that share the same hairpin structure but are anchored with two, three, four and six degenerate nucleotides at 3′-ends (namely UHP2, UHP3, UHP4 and UHP6), and found that the four UHPs yielded robust RT products and quantified miRNAs with high efficiency. UHP-based RT-qPCR miRNA quantification was not affected by long transcripts. By analyzing 14 miRNAs, we demonstrated that UHP4 closely mimicked MsHPs in miRNA quantification. Fine-tuning experiments identified an optimized UHP (OUHP) mix with a molar composition of UHP2:UHP4:UHP6 = 8:1:1, which closely recapitulated MsHPs in miRNA quantification. Using synthetic LET7 isomiRs, we demonstrated that the OUHP-based qPCR system exhibited high specificity and sensitivity. Collectively, our results demonstrate that the OUHP system can serve as a reliable and cost-effective surrogate of MsHPs for RT-qPCR-based miRNA quantification for basic research and precision medicine.

Abstract 12489: Blood Type A1 Donor and Recipient Matching for Heart Transplant: Does It Matter?

Introduction: ABO antibodies bind specific carbohydrate moieties defining the A and B antigens. With blood group A, inter-individual variation in transferase specificity and efficiency results in differential antigen expression and density. These subgroups of A are termed non-A1 and have fewer A antigen epitopes per red blood cell, which is less immunogenic. Our goal was to assess the impact of transplantation of an A1 organ to a non-A1 recipient. Methods: We assessed 138 blood-type A heart transplant recipients transplanted between 2013 and 2020. Comparison groups included a "match" group (A1 donor into A1 recipient, and non-A1 donor into non-A1 recipient, n=88) and a "mismatch" group (A1 donor into non-A1 recipient, and non-A1 donor into A1 recipient, n=50). Outcomes included 1-year survival, freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30%), freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, percutaneous coronary intervention, defibrillator/pacemaker implant, stroke), and 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Results: The mismatch group exhibited similar subsequent 1-year survival, freedom from CAV, and freedom from NF-MACE and subsequent 1-year freedom from ATR, ACR, and AMR compared to the match group. (Table) Conclusions: The mismatch of blood type in A1 and non-A1 between donors and recipients does not adversely affect outcomes after heart transplantation. Selective matching of specific A blood typing for heart transplantation is not necessary.

Defining substrate selection by rhinoviral 2A proteinase through its crystal structure with the inhibitor zVAM.fmk

Picornavirus family members cause disease in humans. Human rhinoviruses (RV), the main causative agents of the common cold, increase the severity of asthma and COPD; hence, effective agents against RVs are required. The 2A proteinase (2Apro), found in all enteroviruses, represents an attractive target; inactivating mutations in poliovirus 2Apro result in an extension of the VP1 protein preventing infectious virion assembly. Variations in sequence and substrate specificity on eIF4G isoforms between RV 2Apro of genetic groups A and B hinder 2Apro as drug targets. Here, we demonstrate that although RV-A2 and RV-B4 2Apro cleave the substrate GAB1 at different sites, the 2Apro from both groups cleave equally efficiently an artificial site containing P1 methionine. We determined the RV-A2 2Apro structure complexed with zVAM.fmk, containing P1 methionine. Analysis of this first 2Apro-inhibitor complex reveals a conserved hydrophobic P4 pocket among enteroviral 2Apro as a potential target for broad-spectrum anti-enteroviral inhibitors.

Lipid profiling suggests species specificity and minimal seasonal variation in Pacific Green and Hawksbill Turtle plasma.

In this study, we applied multiple reaction monitoring (MRM)-profiling to explore the relative ion intensity of lipid classes in plasma samples from sea turtles in order to profile lipids relevant to sea turtle physiology and investigate how dynamic ocean environments affect these profiles. We collected plasma samples from foraging green (Chelonia mydas, n = 28) and hawksbill (Eretmochelys imbricata, n = 16) turtles live captured in North Pacific Costa Rica in 2017. From these samples, we identified 623 MRMs belonging to 10 lipid classes (sphingomyelin, phosphatidylcholine, free fatty acid, cholesteryl ester, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidylethanolamine, ceramide, and triacylglyceride) and one metabolite group (acyl-carnitine) present in sea turtle plasma. The relative ion intensities of most lipids (80%) were consistent between species, across seasons, and were not correlated to body size or estimated sex. Of the differences we observed, the most pronounced was the differences in relative ion intensity between species. We identified 123 lipids that had species-specific relative ion intensities. While some of this variability is likely due to green and hawksbill turtles consuming different food items, we found indications of a phylogenetic component as well. Of these, we identified 47 lipids that varied by season, most belonging to the structural phospholipid classes. Overall, more lipids (n = 39) had higher relative ion intensity in the upwelling (colder) season compared to the non-upwelling season (n = 8). Further, we found more variability in hawksbill turtles than green turtles. Here, we provide the framework in which to apply future lipid profiling in the assessment of health, physiology, and behavior in endangered sea turtles.

A Novel Phage Infecting Alteromonas Represents a Distinct Group of Siphophages Infecting Diverse Aquatic Copiotrophs.

ABSTRACTBacteriophages play critical roles in impacting microbial community succession both ecologically and evolutionarily. Although the majority of phage genetic diversity has been increasingly unveiled, phages infecting members of the ecologically important genus Alteromonas remain poorly understood. Here, we present a comprehensive analysis of a newly isolated alterophage, vB_AcoS-R7M (R7M), to characterize its life cycle traits, genomic features, and putative evolutionary origin. R7M harbors abundant genes identified as host-like auxiliary metabolic genes facilitating viral propagation. Genomic analysis suggested that R7M is distinct from currently known alterophages. Interestingly, R7M was found to share a set of similar characteristics with a number of siphophages infecting diverse aquatic opportunistic copiotrophs. We therefore proposed the creation of one new subfamily (Queuovirinae) to group with these evolutionarily related phages. Notably, tail genes were less likely to be shared among them, and baseplate-related genes varied the most. In-depth analyses indicated that R7M has replaced its distal tail with a Rhodobacter capsulatus gene transfer agent (RcGTA)-like baseplate and further acquired a putative receptor interaction site targeting Alteromonas. These findings suggest that horizontal exchanges of viral tail adsorption apparatuses are widespread and vital for phages to hunt new hosts and to adapt to new niches.IMPORTANCE The evolution and ecology of phages infecting members of Alteromonas, a marine opportunistic genus that is widely distributed and of great ecological significance, remain poorly understood. The present study integrates physiological and genomic evidence to characterize the properties and putative phage-host interactions of a newly isolated Alteromonas phage, vB_AcoS-R7M (R7M). A taxonomic study reveals close evolutionary relationships among R7M and a number of siphophages infecting various aquatic copiotrophs. Their similar head morphology and overall genetic framework suggest their putative common ancestry and the grouping of a new viral subfamily. However, their major difference lies in the viral tail adsorption apparatuses and the horizontal exchanges of which possibly account for variations in host specificity. These findings outline an evolutionary scenario for the emergence of diverse viral lineages of a shared genetic pool and give insights into the genetics and ecology of viral host jumps.

Age-specific cut-off levels of anti-M\xfcllerian hormone can be used as diagnostic markers for polycystic ovary syndrome

BackgroundThe majority of available studies on the AMH thresholds were not age-specific and performed the receiver operating characteristic curve (ROC) analysis, based on variations in sensitivity and specificity rather than positive and negative predictive values (PPV and NPV, respectively), which are more clinically applicable. Moreover, all of these studies used a pre-specified age categorization to report the age-specific cut-off values of AMH.Methods A total of 803 women, including 303 PCOS patients and 500 eumenorrheic non-hirsute control women, were enrolled in the present study. The PCOS group included PCOS women, aged 20–40 years, who were referred to the Reproductive Endocrinology Research Center, Tehran, Iran. The Rotterdam consensus criteria were used for diagnosis of PCOS. The control group was selected among women, aged 20–40 years, who participated in Tehran Lipid and Glucose cohort Study (TLGS). Generalized additive models (GAMs) were used to identify the optimal cut-off points for various age categories. The cut-off levels of AMH in different age categories were estimated, using the Bayesian method.Main results and the role of chanceTwo optimal cut-off levels of AMH (ng/ml) were identified at the age of 27 and 35 years, based on GAMs. The cut-off levels for the prediction of PCOS in the age categories of 20–27, 27–35, and 35–40 years were 5.7 (95 % CI: 5.48–6.19), 4.55 (95 % CI: 4.52–4.64), and 3.72 (95 % CI: 3.55–3.80), respectively. Based on the Bayesian method, the PPV and NPV of these cut-off levels were as follows: PPV = 0.98 (95 % CI: 0.96–0.99) and NPV = 0.40 (95 % CI: 0.30–0.51) for the age group of 20–27 years; PPV = 0.96 (95 % CI: 0.91–0.99) and NPV = 0.82 (95 % CI: 0.78–0.86) for the age group of 27–35 years; and PPV = 0.86 (95 % CI: 0.80–0.94) and NPV = 0.96 (95 % CI: 0.93–0.98) for the age group of 35–40 years.ConclusionsApplication of age-specific cut-off levels of AMH, according to the GAMs and Bayesian method, could elegantly assess the value of AMH in discriminating PCOS patients in all age categories.