Does phenology influence predation rate on Salmo trutta parr during lake migration?

Acoustic tags fitted with predation sensors, which trigger following ingestion by piscivorous predators, were used to compare direct predation rates during downstream migration (out-migration) of potamodromous (freshwater) brown trout (Salmo trutta L.) parr from their natal river into a large freshwater lake system during spring and autumn. Thirty-eight spring migrants were tagged across two study years (2021 and 2022) of which 13 individuals (34%) were predated. By contrast 40 autumn migrants were tagged (2020 and 2021) of which three individuals (7.5%) experienced predation. The overall predation loss rate for spring migrants was 0.342% day-1 and was 0.075% day-1 for autumn migrants. Most predation events during spring (77%) occurred within the lower river before tagged fish entered the lake, whilst no predation events were recorded within the river in the autumn. Predation events were significantly linked to tagging season (spring or autumn), with the probability of tags remaining untriggered (as a proxy for survival) being higher 93% (95% confidence interval [CI] [87%, 100%]) in autumn than in spring 66% (95% CI [53%, 83%]). The spring migration periods showed significantly lower river discharge (0.321 m3 /s mean daily discharge, April 1 to May 31) to those measured during autumn (1.056 m3 /s mean daily discharge, October 1 to November 30) (Mann-Whitney U-test, U = 1149, p < 0.001). Lower flows, clearer water, and longer sojourn in the river may have contributed to greater predation losses in the spring relative to the autumn.

Investigating the phenology of juvenile potamodromous brown trout (Salmo trutta L.) in two large lake catchments.

There is growing interest in the phenology of juvenile Salmo trutta and evidence of significant downstream migration during the autumn in some anadromous populations. The present study used acoustic telemetry to examine the phenology of potamodromous trout parr across a region encompassing two large lake catchments. One hundred sixty-seven trout parr were tagged in late summer across four lake tributaries between 2018 and 2020. In total, 75 tagged parr migrated into the lakes with 67 (89%) migrating between September and December and 8 (11%) migrating between March and June. Autumn migration was highly prevalent across all the tributaries, with 16%-66% of each tagged sample exhibiting autumn migration, and 0%-15% of each tagged sample exhibiting spring migration. Autumn migrants were significantly longer and heavier than spring migrants, but condition factor was similar. Autumn migrants were associated with higher river discharge levels and lower water temperatures than spring migrants. The management challenges posed by extensive autumn migration behaviour in migratory trout stocks are examined and discussed.

Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling.

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients' serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.

River lamprey present an unusual predation threat to Atlantic salmon smolts in Lough Neagh, Northern Ireland.

A new monitoring programme on the Lough Neagh catchment has documented a high incidence of river lamprey, Lampetra fluviatilis L., predation on Atlantic salmon smolts, Salmo salar L. In total 470 smolts were examined during the 2020 emigration period with 168 fish (36%) exhibiting lamprey scars of which 57 were lightly scarred and 111 were classed as heavily scarred. Lamprey predation was not size selective on Lough Neagh S. salar smolts.

Long-term retention of dummy acoustic transmitters in adult brown trout.

A group of 36 1+ age class Salmo trutta were surgically implanted with dummy acoustic tags and monitored for 370 days. In total 13 tags were expelled throughout the experiment with an overall tag loss rate of c. 0.035 tags per day. Fish length was the only explanatory variable which had a significant association with subsequent tag expulsion. The estimated probability of retaining a tag for a year for a fish of length 32 cm was 0.76, 34 cm was 0.60 and 36 cm was 0.38. The long-term tag loss patterns were examined and discussed.

Understanding microcystin-LR antibody binding interactions using in silico docking and in vitro mutagenesis.

Microcystins (MCs) are a group of highly potent cyanotoxins that are becoming more widely distributed due to increased global temperatures and climate change. Microcystin-leucine-arginine (MC-LR) is the most potent and most common variant, with a guideline limit of 1 µg/l in drinking water. We previously developed a novel avian single-chain fragment variable (scFv), designated 2G1, for use in an optical-planar waveguide detection system for microcystin determination. This current work investigates interactions between 2G1 and MC-LR at the molecular level through modelling with an avian antibody template and molecular docking by AutoDock Vina to identify key amino acid (AA) residues involved. These potential AA interactions were investigated in vitro by targeted mutagenesis, specifically, by alanine scanning mutations. Glutamic acid (E) was found to play a critical role in the 2G1-MC-LR binding interaction, with the heavy chain glutamic acid (E) 102 (H-E102) forming direct bonds with the arginine (R) residue of MC-LR. In addition, alanine mutation of light chain residue aspartic acid 57 (L-D57) led to an improvement in antigen-binding observed using enzyme-linked immunosorbent assay (ELISA), and was confirmed by surface plasmon resonance (SPR). This work will contribute to improving the binding of recombinant anti-MC-LR to its antigen and aid in the development of a higher sensitivity harmful algal toxin diagnostic.

Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer.

Classifying indolent prostate cancer represents a significant clinical challenge. We investigated whether integrating data from different omic platforms could identify a biomarker panel with improved performance compared to individual platforms alone. DNA methylation, transcripts, protein and glycosylation biomarkers were assessed in a single cohort of patients treated by radical prostatectomy. Novel multiblock statistical data integration approaches were used to deal with missing data and modelled via stepwise multinomial logistic regression, or LASSO. After applying leave-one-out cross-validation to each model, the probabilistic predictions of disease type for each individual panel were aggregated to improve prediction accuracy using all available information for a given patient. Through assessment of three performance parameters of area under the curve (AUC) values, calibration and decision curve analysis, the study identified an integrated biomarker panel which predicts disease type with a high level of accuracy, with Multi AUC value of 0.91 (0.89, 0.94) and Ordinal C-Index (ORC) value of 0.94 (0.91, 0.96), which was significantly improved compared to the values for the clinical panel alone of 0.67 (0.62, 0.72) Multi AUC and 0.72 (0.67, 0.78) ORC. Biomarker integration across different omic platforms significantly improves prediction accuracy. We provide a novel multiplatform approach for the analysis, determination and performance assessment of novel panels which can be applied to other diseases. With further refinement and validation, this panel could form a tool to help inform appropriate treatment strategies impacting on patient outcome in early stage prostate cancer.

Migration and survival of Atlantic salmon Salmo salar smolts in a large natural lake.

An investigation with acoustic telemetry of the passage of Salmo salar smolts through a large natural lake found heavy mortality occurred at the river-to-lake confluences (mean 31.2% km-1 ), but was lower in the main body of the lake (mean 2.4% km-1 ). Predation was a significant pressure on emigrating smolts as tagged pike Esox lucius aggregated at river-to-lake confluences during the peak of the smolt run. Tagged smolts mainly emmigrated into the lake in the late evening after dusk, possibly as a predator-avoidance behaviour.

Biosensors for the monitoring of harmful algal blooms.

Harmful algal blooms (HABs) are a major global concern due to their propensity to cause environmental damage, healthcare issues and economic losses. In particular, the presence of toxic phytoplankton is a cause for concern. Current HAB monitoring programs often involve laborious laboratory-based analysis at a high cost and with long turnaround times. The latter also hampers the potential to develop accurate and reliable models that can predict HAB occurrence. However, a promising solution for this issue may be in the form of remotely deployed biosensors, which can rapidly and continuously measure algal and toxin levels at the point-of-need (PON), at a low cost. This review summarises the issues HABs present, how they are difficult to monitor and recently developed biosensors that may improve HAB-monitoring challenges.

Comprehensive N-Glycan Profiling of Avian Immunoglobulin Y.

Recent exploitation of the avian immune system has highlighted its suitability for the generation of high-quality, high-affinity antibodies to a wide range of antigens for a number of therapeutic and biotechnological applications. The glycosylation profile of potential immunoglobulin therapeutics is species specific and is heavily influenced by the cell-line/culture conditions used for production. Hence, knowledge of the carbohydrate moieties present on immunoglobulins is essential as certain glycan structures can adversely impact their physicochemical and biological properties. This study describes the detailed N-glycan profile of IgY polyclonal antibodies from the serum of leghorn chickens using a fully quantitative high-throughput N-glycan analysis approach, based on ultra-performance liquid chromatography (UPLC) separation of released glycans. Structural assignments revealed serum IgY to contain complex bi-, tri- and tetra-antennary glycans with or without core fucose and bisects, hybrid and high mannose glycans. High sialic acid content was also observed, with the presence of rare sialic acid structures, likely polysialic acids. It is concluded that IgY is heavily decorated with complex glycans; however, no known non-human or immunogenic glycans were identified. Thus, IgY is a potentially promising candidate for immunoglobulin-based therapies for the treatment of various infectious diseases.

Antibodies and antibody-derived analytical biosensors.

The rapid diagnosis of many diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Biosensors are now being applied for rapid diagnostics due to their capacity for point-of-care use with minimum need for operator input. Antibody-based biosensors or immunosensors have revolutionized diagnostics for the detection of a plethora of analytes such as disease markers, food and environmental contaminants, biological warfare agents and illicit drugs. Antibodies are ideal biorecognition elements that provide sensors with high specificity and sensitivity. This review describes monoclonal and recombinant antibodies and different immobilization approaches crucial for antibody utilization in biosensors. Examples of applications of a variety of antibody-based sensor formats are also described.

Use of biosensors for the detection of marine toxins.

Increasing occurrences of harmful algal blooms (HABs) in the ocean are a major concern for countries around the globe, and with strong links between HABs and climate change and eutrophication, the occurrences are only set to increase. Of particular concern with regard to HABs is the presence of toxin-producing algae. Six major marine biotoxin groups are associated with HABs. Ingestion of such toxins via contaminated shellfish, fish, or other potential vectors, can lead to intoxication syndromes with moderate to severe symptoms, including death in extreme cases. There are also major economic implications associated with the diverse effects of marine biotoxins and HABs. Thus, effective monitoring programmes are required to manage and mitigate their detrimental global effect. However, currently legislated detection methods are labour-intensive, expensive and relatively slow. The growing field of biosensor diagnostic devices is an exciting area that has the potential to produce robust, easy-to-use, cost-effective, rapid and accurate detection methods for marine biotoxins and HABs. This review discusses recently developed biosensor assays that target marine biotoxins and their microbial producers, both in harvested fish/shellfish samples and in the open ocean. The effective deployment of such biosensor platforms could address the pressing need for improved monitoring of HABs and marine biotoxins, and could help to reduce their global economic impact.

The need for effective pancreatic cancer detection and management: a biomarker-based strategy.

Pancreatic cancer (Pa) is generally a very aggressive disease, with few effective approaches available for early diagnosis or therapy. These factors, combined with the aggressiveness and chemoresistance of Pa, results in a bleak outcome post-diagnosis. Cancer-related biomarkers have established capabilities for diagnosis, prognosis and screening and can be exploited to aid in earlier less-invasive diagnosis and optimization of targeted therapies. Pa has only one US FDA-approved biomarker, CA19-9, which has significant limitations. Hence, it is vital that novel biomarkers are identified and validated to diagnose, treat, control and monitor Pa. This review focuses on existing and potential Pa-associated markers and discusses how they may be applied in cohort for improved management of Pa.

Detection of the cyanobacterial toxin, microcystin-LR, using a novel recombinant antibody-based optical-planar waveguide platform.

Microcystins are a major group of cyanobacterial heptapeptide toxins found in freshwater and brackish environments. There is currently an urgent requirement for highly-sensitive, rapid and in-expensive detection methodologies for these toxins. A novel single chain fragment variable (scFv) fragment was generated and is the first known report of a recombinant anti-microcystin avian antibody. In a surface plasmon resonance-based immunoassay, the antibody fragment displayed cross-reactivity with seven microcystin congeners (microcystin-leucine-arginine (MC-LR) 100%, microcystin-tyrosine-arginine (MC-YR) 79.7%, microcystin-leucine-alanine (MC-LA) 74.8%, microcystin-leucine-phenylalanine (MC-LF) 67.5%, microcystin-leucine-tryptophan (MC-LW) 63.7%, microcystin-arginine-arginine (MC-RR) 60.1% and nodularin (Nod) 69.3%, % cross reactivity). Following directed molecular evolution of the parental clone the resultant affinity-enhanced antibody fragment was applied in an optimized fluorescence immunoassay on a planar waveguide detection system. This novel immuno-sensing format can detect free microcystin-LR with a functional limit of detection of 0.19 ng mL(-1)and a detection range of 0.21-5.9 ng mL(-1). The assay is highly reproducible (displaying percentage coefficients of variance below 8% for intra-day assays and below 11% for inter-day assays), utilizes an inexpensive cartridge system with low reagent volumes and can be completed in less than twenty minutes.

Point-of-care diagnostics, a major opportunity for change in traditional diagnostic approaches: potential and limitations.

'Point-of-care' (POC) diagnostics are a powerful emerging healthcare approach. They can rapidly provide statistically significant results, are simple to use, do not require specialized equipment and are cost-effective. For these reasons, they have the potential to play a major role in revolutionizing the diagnosis, initiation and monitoring of treatment of major global diseases. This review focuses on antibody-based POC devices that target four major global diseases: cardiovascular diseases, prostate cancer, HIV infection and tuberculosis. The key statistics and pathology of each disease is described in detail, followed by an in-depth discussion on emerging POC devices that target each disease, highlighting their potential and limitations.

Reconciling the structural attributes of avian antibodies.

Antibodies are high value therapeutic, diagnostic, biotechnological, and research tools. Combinatorial approaches to antibody discovery have facilitated access to unique antibodies by surpassing the diversity limitations of the natural repertoire, exploitation of immune repertoires from multiple species, and tailoring selections to isolate antibodies with desirable biophysical attributes. The V-gene repertoire of the chicken does not utilize highly diverse sequence and structures, which is in stark contrast to the mechanism employed by humans, mice, and primates. Recent exploitation of the avian immune system has generated high quality, high affinity antibodies to a wide range of antigens for a number of therapeutic, diagnostic and biotechnological applications. Furthermore, extensive examination of the amino acid characteristics of the chicken repertoire has provided significant insight into mechanisms employed by the avian immune system. A paucity of avian antibody crystal structures has limited our understanding of the structural consequences of these uniquely chicken features. This paper presents the crystal structure of two chicken single chain fragment variable (scFv) antibodies generated from large libraries by phage display against important human antigen targets, which capture two unique CDRL1 canonical classes in the presence and absence of a non-canonical disulfide constrained CDRH3. These structures cast light on the unique structural features of chicken antibodies and contribute further to our collective understanding of the unique mechanisms of diversity and biochemical attributes that render the chicken repertoire of particular value for antibody generation.

Basin-scale phenology and effects of climate variability on global timing of initial seaward migration of Atlantic salmon (Salmo salar).

Migrations between different habitats are key events in the lives of many organisms. Such movements involve annually recurring travel over long distances usually triggered by seasonal changes in the environment. Often, the migration is associated with travel to or from reproduction areas to regions of growth. Young anadromous Atlantic salmon (Salmo salar) emigrate from freshwater nursery areas during spring and early summer to feed and grow in the North Atlantic Ocean. The transition from the freshwater ('parr') stage to the migratory stage where they descend streams and enter salt water ('smolt') is characterized by morphological, physiological and behavioural changes where the timing of this parr-smolt transition is cued by photoperiod and water temperature. Environmental conditions in the freshwater habitat control the downstream migration and contribute to within- and among-river variation in migratory timing. Moreover, the timing of the freshwater emigration has likely evolved to meet environmental conditions in the ocean as these affect growth and survival of the post-smolts. Using generalized additive mixed-effects modelling, we analysed spatio-temporal variations in the dates of downstream smolt migration in 67 rivers throughout the North Atlantic during the last five decades and found that migrations were earlier in populations in the east than the west. After accounting for this spatial effect, the initiation of the downstream migration among rivers was positively associated with freshwater temperatures, up to about 10 °C and levelling off at higher values, and with sea-surface temperatures. Earlier migration occurred when river discharge levels were low but increasing. On average, the initiation of the smolt seaward migration has occurred 2.5 days earlier per decade throughout the basin of the North Atlantic. This shift in phenology matches changes in air, river, and ocean temperatures, suggesting that Atlantic salmon emigration is responding to the current global climate changes.

A tale of two specificities: bispecific antibodies for therapeutic and diagnostic applications.

Artificial manipulation of antibody genes has facilitated the production of several unique recombinant antibody formats, which have highly important therapeutic and biotechnological applications. Although bispecific antibodies (bsAbs) are not new, they are coming to the forefront as our knowledge of the potential efficacy of antibody-based therapeutics expands. The next generation of bsAbs is developing due to significant improvements in recombinant antibody technologies. This review focuses on recent advances with a particular focus on improvements in format and design that are contributing to the resurgence of bsAbs, and in particular, on innovative structures applicable to next generation point-of-care (POC) devices with applicability to low resource environments.

Aberrant PSA glycosylation--a sweet predictor of prostate cancer.

Prostate cancer--the most commonly diagnosed cancer in men worldwide--can have a substantial effect on quality of life, regardless of the route the cancer takes. The serum PSA assay is the current gold standard option for diagnosing prostate cancer. However, a growing body of evidence suggests that PSA screening for prostate cancer results in extensive overdiagnosis and overtreatment. It is increasingly evident that the potential harm from overdiagnosis (in terms of unnecessary biopsies) must be weighed against the benefit derived from the early detection and treatment of potentially fatal prostate cancers. Rapid screening methods have been used to analyse glycosylation patterns on glycoproteins in large cohorts of patients, enabling the identification of a new generation of disease biomarkers. Changes to the expression status of certain glycan structures are now widely thought to be common features of tumour progression. In light of this development, much research has focused on the potential role of altered PSA glycosylation patterns in discriminating between significant and insignificant prostate cancers, with the aim of developing a more reliable diagnostic tool than the current serum PSA test.

Quality of life among acoustic neuroma patients managed by microsurgery, radiation, or observation.

OBJECTIVE: The main aim of this study was to examine differences in quality of life (QoL) among acoustic neuroma patients across the management options of microsurgery, radiation, and observation. Additional aims were to describe QoL and investigate management, medical, and demographic factors that predicted QoL in this patient group. STUDY DESIGN: Cross-sectional design, using a postal questionnaire. SETTING: Tertiary referral centers. PATIENTS: Participants included 180 adults diagnosed with, or treated for, a unilateral acoustic neuroma within 5 years of questionnaire distribution. The mean age of participants was 56.5 years, and 107 (59.4%) were female. INTERVENTION(S): Patients' acoustic neuromas were managed with microsurgery, radiation, or observation. MAIN OUTCOME MEASURE(S): Current QoL was measured using the Short Form 12 Version 2 (SF-12), and postmanagement changes in QoL were assessed with the Glasgow Benefit Inventory (GBI). RESULTS: No significant differences in SF-12 scores were found across microsurgery, radiation, and observation patients. However, microsurgery patients reported more deterioration on the GBI general well-being subscale than radiation patients and more improvement in the GBI social support scale than observation patients. Number of symptoms was a consistent predictor of SF-12 and GBI scores. CONCLUSION: This is only the second study to use multivariate statistical techniques and a large sample to examine QoL across the acoustic neuroma management options of microsurgery, radiation, and observation. There were few differences in QoL outcomes across management groups. Number of symptoms was an important factor in current QoL and postmanagement changes in QoL.