The Schistosoma mansoni tegumental-allergen-like (TAL) protein family: influence of developmental expression on human IgE responses

BACKGROUND: A human IgE response to Sm22.6 (a dominant IgE target in Schistosoma mansoni) is associated with the development of partial immunity. Located inside the tegument, the molecule belongs to a family of proteins from parasitic platyhelminths, the Tegument-Allergen-Like proteins (TALs). In addition to containing dynein-light-chain domains, these TALs also contain EF-hand domains similar to those found in numerous EF-hand allergens. METHODOLOGY/PRINCIPAL FINDINGS: S. mansoni genome searches revealed 13 members (SmTAL1-13) within the species. Recent microarray data demonstrated they have a wide range of life-cycle transcriptional profiles. We expressed SmTAL1 (Sm22.6), SmTAL2, 3, 4, 5 and 13 as recombinant proteins and measured IgE and IgG4 in 200 infected males (7–60 years) from a schistosomiasis endemic region in Uganda. For SmTAL1 and 3 (transcribed in schistosomula through adult-worms and adult-worms, respectively) and SmTAL5 (transcribed in cercariae through adult-worms), detectable IgE responses were rare in 7–9 year olds, but increased with age. At all ages, IgE to SmTAL2 (expressed constitutively), was rare while anti-SmTAL2 IgG4 was common. Levels of IgE and IgG4 to SmTAL4 and 13 (transcribed predominantly in the cercariae/skin stage) were all low. CONCLUSIONS: We have not measured SmTAL protein abundance or exposure in live parasites, but the antibody data suggests to us that, in endemic areas, there is priming and boosting of IgE to adult-worm SmTALs by occasional death of long-lived worms, desensitization to egg SmTALs through continuous exposure to dying eggs and low immunogenicity of larval SmTALs due to immunosuppression in the skin by the parasite. Of these, it is the gradual increase in IgE to the worm antigens that parallels age-dependent immunity seen in endemic areas

Rhodolith Beds Are Major CaCO3 Bio-Factories in the Tropical South West Atlantic

Rhodoliths are nodules of non-geniculate coralline algae that occur in shallow waters (<150 m depth) subjected to episodic disturbance. Rhodolith beds stand with kelp beds, seagrass meadows, and coralline algal reefs as one of the world's four largest macrophyte-dominated benthic communities. Geographic distribution of rhodolith beds is discontinuous, with large concentrations off Japan, Australia and the Gulf of California, as well as in the Mediterranean, North Atlantic, eastern Caribbean and Brazil. Although there are major gaps in terms of seabed habitat mapping, the largest rhodolith beds are purported to occur off Brazil, where these communities are recorded across a wide latitudinal range (2°N - 27°S). To quantify their extent, we carried out an inter-reefal seabed habitat survey on the Abrolhos Shelf (16°50′ - 19°45′S) off eastern Brazil, and confirmed the most expansive and contiguous rhodolith bed in the world, covering about 20,900 km2. Distribution, extent, composition and structure of this bed were assessed with side scan sonar, remotely operated vehicles, and SCUBA. The mean rate of CaCO3 production was estimated from in situ growth assays at 1.07 kg m−2 yr−1, with a total production rate of 0.025 Gt yr−1, comparable to those of the world's largest biogenic CaCO3 deposits. These gigantic rhodolith beds, of areal extent equivalent to the Great Barrier Reef, Australia, are a critical, yet poorly understood component of the tropical South Atlantic Ocean. Based on the relatively high vulnerability of coralline algae to ocean acidification, these beds are likely to experience a profound restructuring in the coming decades

Alignment of amino acids sequences of the SmTAL family.

<p>Helix-loop-helix EF-hand domains (Pfam00036) are indicated. The canonical aspartic acid residues at the start of the loop are denoted D on black background. Residues in the dynein light chain domain (EMBL/EBI IPR001372) are shaded grey. Alignment was performed using Clustal W.</p

Antibody responses to SmTAL1, SmTAL3 and SmTAL5 in the <i>S. mansoni</i> infected cohort.

<p>Recombinant SmTAL1, 3 and 5 were used in ELISA to measure antigen-specific IgE (<b>A</b>) or IgG4 (<b>B</b>) before and after praziquantel treatment in 200 males infected with <i>S. mansoni</i>. Only individuals whose levels exceeded the seropositive threshold (mean+3xSD uninfected controls) for each response are graphed. For the whole cohort, the prevalence of each response (<b>C</b>) is shown in 5 age groups, 7–9 (n = 36), 10–14 (n = 43), 15–24 (n = 35), 25–34 (n = 43) and 35–60 (n = 43) Shown is % seropositive for each group after treatment +95% confidence intervals.</p

Transcription profiles of SmTALs.

<p>Profiles from the <i>S. mansoni</i> lifecycle microarray data available via Array express (31) under the experimental accession number E-MEXP-2094. Values are mean normalized fluorescence units ± sem. In primate infections, larvae remain in the skin for 2–5 days (Wilson et al. 1990). In the figure cercariae to 3 d schistosomula are denoted “skin stage”.</p

Electrophoresis of purified SmTAL proteins.

<p>2 µg of each of the indicated proteins was run under reducing conditions on a 4–12% gradient SDS-PAGE gel and stained with Coomassie blue.</p

Expression of SmTAL4 in cercarial tail only.

<p>For PCR analysis (<b>A</b>), total RNA from isolated from heads (H) and tails (T) after mechanical separation and used to prepare cDNA for use with specific primers to generate amplicons for Sm ß-actin (203 bp), SmTAL4 (152 bp), SmTAL5(228 bp) and SmTAL13(206 bp). Products were separated on a 2% agarose gel and detected with ethidium bromide. For immunostaining (<b>B</b>) 8 µ sections of frozen sections of whole cercariae were fixed and stained with rat anti-SmTAL4 antiserum and TRITC -anti-rat antibody (red). Nuclei were counterstained with DAPI (blue). In the negative control (insert) anti- SmTAL4 antiserum was pre-absorbed with recombinant SmTAL4.</p

Proceedings of the Survivorship Care in Neuro-Oncology Workshop sponsored by the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT).

BackgroundSurvivorship for those living with primary CNS cancers begins at diagnosis, continues throughout a person's life, and includes caregivers. Opportunities and challenges exist to advance survivorship care for those living with primary CNS cancers that necessitate stakeholder involvement.MethodsIn June 2021, NCI-CONNECT convened a two-day virtual workshop about survivorship care in neuro-oncology. Two expert panels provided key recommendations and five working groups considered critical questions to identify strengths, weaknesses, opportunities, and threats to the advancement of survivorship care and developed recommendations and action items.ResultsThe following action items emanated from the workshop: seek endorsement of meeting report from stakeholder organizations; address barriers in access to survivorship care and provider reimbursement; advance survivorship research through NIH and private grant support; develop a survivorship tool kit for providers, people living with primary CNS cancers and their caregivers; provide accessible educational content for neuro-oncology, neurology, and oncology community providers about survivorship care in neuro-oncology; and establish core competencies for survivorship care for neuro-oncology providers to be included in training and standardized exams.ConclusionsAction items aim to address access and reimbursement barriers, expand patient and provider education, develop core competencies, and support survivorship research through funding and other supports