The Strength of B Cell Interaction with Antigen Determines the Degree of IgM Polymerization

The induction of variable disulfide polymerization of IgM in the trout (Oncorhynchus mykiss) and its effect on its half-life were examined. An association between greater Ab affinity and increased disulfide polymerization was first indicated by the observation of this increased IgM disulfide polymerization during the process of affinity maturation. A direct association between Ab affinity and disulfide polymerization was then established by the fractionation of individual sera into high- and low-affinity subpopulations, which also resulted in the partitioning of high and low degrees of disulfide polymerization. The ability of high-affinity B cells to produce more highly polymerized Abs upon Ag induction was demonstrated by in vitro Ag-driven selection. Low Ag concentrations, which elicited only high-affinity Abs, also possessed the highest degree of polymerization, whereas higher concentrations of Ag elicited a broader array of Ab affinities, yielding a lower average affinity and degree of polymerization. Half-life studies revealed that the high-affinity, highly polymerized Abs possessed longer half-lives than the lower-affinity, lightly polymerized Abs. Finally, although the affinity for Ag is associated with elevated levels of polymerization, analysis of naive Ig revealed that the degree of polymerization alone, not affinity, appears sufficient to prolong Ig half-life. The Journal of Immunology, 2010,184: 844-850

Evolution of the capsular operon of Streptococcus iniae in response to vaccination

Streptococcus iniae causes severe septicemia and meningitis in farmed fish and is also occasionally zoonotic. Vaccination against S. iniae is problematic, with frequent breakdown of protection in vaccinated fish. The major protective antigens in S. iniae are the polysaccharides of the capsule, which are essential for virulence. Capsular biosynthesis is driven and regulated by a 21-kb operon comprising up to 20 genes. In a long-term study, we have sequenced the capsular operon of strains that have been used in autogenous vaccines across Australia and compared it with the capsular operon sequences of strains subsequently isolated from infected vaccinated fish. Intriguingly, strains isolated from vaccinated fish that subsequently become infected have coding mutations that are confined to a limited number of genes in the cps operon, with the remainder of the genes in the operon remaining stable. Mutations in strains in diseased vaccinated fish occur in key genes in the capsular operon that are associated with polysaccharide configuration (cpsG) and with regulation of biosynthesis (cpsD and cpsE). This, along with high ratios of nonsynonymous to synonymous mutations within the cps genes, suggests that immune response directed predominantly against capsular polysaccharide may be driving evolution in a very specific set of genes in the operon. From these data, it may be possible to design a simple polyvalent vaccine with a greater operational life span than the current monovalent killed bacterins

Description of Goussia kuehae n. sp. (Apicomplexa: Eimeriidae) infecting the Asian seabass, Lates calcarifer (Bloch)(Perciformes: Latidae), cultured in Malaysian fish farms

Culturing fishes in marine cages is a rapidly developing area of marine aquaculture. The Asian seabass Lates calcarifer (Bloch) is a fast growing good quality fish that is readily cultured in intensive systems in the South Asian region and in Malaysia in particular. Although several papers have been published to date on viral, bacterial, parasitic and fungal organisms causing diseases in the Asian seabass, the occurrence of a coccidian infection in this species has only recently been recorded. We collected sporulated and unsporulated oo¨cysts of a new species of Goussia Labbe´, 1986, from the mucus covering the epithelium of the intestine of L. calcarifer. This paper provides a description of Goussia kuehae n. sp. Sporulated oo¨cysts of this species are ellipsoidal, 37–40 lm in length and 28–30 lm in width. The ellipsoidal sporocysts are relatively small, 15.2–17 9 5.7–8 lm, and located loosely in the oo¨cyst. There are residual bodies both in the oo¨cysts and the sporocysts. Goussia kuehae n. sp. differs from all known species of Goussia in the large size of the oo¨cysts and in having two types of oo¨cyst residuum

Detection of hexavalent uranium with inline and field-portable immunosensors

An antibody that recognizes a chelated form of hexavalent uranium was used in the development of two different immunosensors for uranium detection. Specifically, these sensors were utilized for the analysis of groundwater samples collected during a 2007 field study of in situ bioremediation in a aquifer located at Rifle, CO. The antibody-based sensors provided data comparable to that obtained using Kinetic Phosphorescence Analysis (KPA). Thus, these novel instruments and associated reagents should provide field researchers and resource managers with valuable new tools for on-site data acquisition

Dietary tuna hydrolysate modulates growth performance, immune response, intestinal morphology and resistance to Streptococcus iniae in juvenile barramundi, Lates calcarifer

This study investigated the effects of tuna hydrolysate (TH) inclusion in fishmeal (FM) based diets on the growth performance, innate immune response, intestinal health and resistance to Streptococcus iniae infection in juvenile barramundi, Lates calcarifer. Five isonitrogenous and isoenergetic experimental diets were prepared with TH, replacing FM at levels of 0% (control) 5%, 10%, 15% and 20%, and fed fish to apparent satiation three times daily for 8 weeks. The results showed that fish fed diets containing 5% and 10% TH had significantly higher final body weight and specific growth rate than the control. A significant reduction in blood glucose was found in fish fed 10%, 15% and 20% TH compared to those in the control whereas none of the other measured blood and serum indices were influenced by TH inclusion. Histological observation revealed a significant enhancement in goblet cell numbers in distal intestine of fish fed 5 to 10% TH in the diet. Moreover, fish fed 10% TH exhibited the highest resistance against Streptococcus iniae infection during a bacterial challenge trial. These findings therefore demonstrate that the replacement of 5 to 10% FM with TH improves growth, immune response, intestinal health and disease resistance in juvenile barramundi

Melatonin Induces Follicle Maturation in Danio rerio

Most organisms modulate their reproductive activity responding to day length by the nocturnal release of melatonin by the pineal gland. This hormone is also responsible for synchronizing reproduction with specific external environment stimuli in order to optimize reproductive success

Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study

Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods: This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926. Findings: Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation: Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services. Funding: National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

Appositional enamel growth in molars of South African fossil hominids

Enamel is formed incrementally by the secretory activity of ameloblast cells. Variable stages of secretion result in the formation of structures known as cross striations along enamel prisms, for which experimental data demonstrate a correspondence with daily periods of secretion. Patterns of variation in this daily growth are important to understanding mechanisms of tooth formation and the development of enamel thickness. Transmitted light microscopy (TLM) of histological ground sections and scanning electron microscopy (SEM) of bulk specimens or their surface replicas are the usual methods for investigating cross striations. However, these methods pose some constraints on the study of these features in Plio-Pleistocene hominid enamel, the specimens of which may only rarely be sectioned for TLM or examined on only their most superficial surfaces for SEM. The recent development of portable confocal scanning optical microscopy (PCSOM) resolves some of the restrictions on fractured enamel surfaces, allowing the visualization of cross striations by direct examination. This technology has been applied here to the study of Australopithecus africanus and Paranthropus robustus hominid molars from the Plio-Pleistocene of South Africa. We hypothesize that these taxa have increased enamel appositional rates compared with modern humans, because despite having thicker enamelled molars (particularly P. robustus), the enamel crowns of these fossil taxa take an equivalent or reduced amount of time to form. Cross striations were measured in cuspal, lateral and cervical regions of the enamel crowns, and, within each region, the inner, middle and outer zones. Values obtained for A. africanus outer zones of the enamel crown are, in general, lower than those for P. robustus, indicating faster forming enamel in the latter, while both taxa show higher rates of enamel growth than modern humans and the African great apes. This demonstrates a relatively high degree of variability in the mechanisms underlying the development of enamel across taxa