Severe Primary Hyperparathyroidism Caused by Parathyroid Carcinoma in a 13‐Year‐Old Child; Novel Findings From HRpQCT

Primary hyperparathyroidism is a condition that occurs infrequently in children. Parathyroid carcinoma, as the underlying cause of hyperparathyroidism in this age group, is extraordinarily rare, with only a few cases reported in the literature. We present a 13-year-old boy with musculoskeletal pain who was found to have brown tumors from primary hyperparathyroidism caused by parafibromin-immunodeficient parathyroid carcinoma. Our patient had no clinical, biochemical, or radiographic evidence of pituitary adenomas, pancreatic tumors, thyroid tumors, pheochromocytoma, jaw tumors, renal abnormalities, or testicular lesions. Germline testing for AP2S1, CASR, CDC73/HRPT2, CDKN1B, GNA11, MEN1, PTH1R, RET, and the GCM2 gene showed no pathological variants, and a microarray of CDC73/HRPT2 did not reveal deletion or duplication. He was managed with i.v. fluids, calcitonin, pamidronate, and denosumab prior to surgery to stabilize hypercalcemia. After removal of a single parathyroid tumor, he developed severe hungry bone syndrome and required 3 weeks of continuous i.v. calcium infusion, in addition to oral calcium and activated vitamin D. Histopathological examination identified an angioinvasive parathyroid carcinoma with global loss of parafibromin (protein encoded by CDC73/HRPT2).HRpQCT and DXA studies were obtained prior to surgery and 18-months postsurgery. HRpQCT showed a resolution of osteolytic lesions combined with structural improvement of cortical porosity and an increase in both cortical thickness and density compared with levels prior to treatment. These findings highlight the added value of HRpQCT in primary hyperparathyroidism. In addition to our case, we have provided a review of the published cases of parathyroid cancer in children

Introducing a new breed of wine yeast: interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast and Saccharomyces mikatae

Interspecific hybrids are commonplace in agriculture and horticulture; bread wheat and grapefruit are but two examples. The benefits derived from interspecific hybridisation include the potential of generating advantageous transgressive phenotypes. This paper describes the generation of a new breed of wine yeast by interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast strain and Saccharomyces mikatae, a species hitherto not associated with industrial fermentation environs. While commercially available wine yeast strains provide consistent and reliable fermentations, wines produced using single inocula are thought to lack the sensory complexity and rounded palate structure obtained from spontaneous fermentations. In contrast, interspecific yeast hybrids have the potential to deliver increased complexity to wine sensory properties and alternative wine styles through the formation of novel, and wider ranging, yeast volatile fermentation metabolite profiles, whilst maintaining the robustness of the wine yeast parent. Screening of newly generated hybrids from a cross between a S. cerevisiae wine yeast and S. mikatae (closely-related but ecologically distant members of the Saccharomyces sensu stricto clade), has identified progeny with robust fermentation properties and winemaking potential. Chemical analysis showed that, relative to the S. cerevisiae wine yeast parent, hybrids produced wines with different concentrations of volatile metabolites that are known to contribute to wine flavour and aroma, including flavour compounds associated with non-Saccharomyces species. The new S. cerevisiae x S. mikatae hybrids have the potential to produce complex wines akin to products of spontaneous fermentation while giving winemakers the safeguard of an inoculated ferment.Jennifer R. Bellon, Frank Schmid, Dimitra L. Capone, Barbara L. Dunn, Paul J. Chamber

Pain Coping Skills Training for African Americans With Osteoarthritis Study: Baseline Participant Characteristics and Comparison to Prior Studies

Background: The Pain Coping Skills Training for African Americans with OsteoaRTthritis (STAART) trial is examining the effectiveness of a culturally enhanced pain coping skills training (CST) program for African Americans with osteoarthritis (OA). This disparities-focused trial aimed to reach a population with greater symptom severity and risk factors for poor pain-related outcomes than previous studies. This paper compares characteristics of STAART participants with prior studies of CST or cognitive behavioral therapy (CBT)-informed training in pain coping strategies for OA. Methods: A literature search identified 10 prior trials of pain CST or CBT-informed pain coping training among individuals with OA. We descriptively compared characteristics of STAART participants with other studies, in 3 domains of the National Institutes of Minority Health and Health Disparities' Research Framework: Sociocultural Environment (e.g., age, education, marital status), Biological Vulnerability and Mechanisms (e.g, pain and function, body mass index), and Health Behaviors and Coping (e.g., pain catastrophizing). Means and standard deviations (SDs) or proportions were calculated for STAART participants and extracted from published manuscripts for comparator studies. Results: The mean age of STAART participants, 59 years (SD = 10.3), was lower than 9 of 10 comparator studies; the proportion of individuals with some education beyond high school, 75%, was comparable to comparator studies (61-86%); and the proportion of individuals who are married or living with a partner, 42%, was lower than comparator studies (62-66%). Comparator studies had less than about 1/3 African American participants. Mean scores on the Western Ontario and McMaster Universities Osteoarthritis Index pain and function scales were higher (worse) for STAART participants than for other studies, and mean body mass index of STAART participants, 35.2 kg/m2 (SD = 8.2), was higher than all other studies (30-34 kg/m2). STAART participants' mean score on the Pain Catastrophizing scale, 19.8 (SD = 12.3), was higher (worse) than other studies reporting this measure (7-17). Conclusions: Compared with prior studies with predominantly white samples, STAART participants have worse pain and function and more risk factors for negative pain-related outcomes across several domains. Given STAART participants' high mean pain catastrophizing scores, this sample may particularly benefit from the CST intervention approach

Tyrosine Sulfation of the Amino Terminus of PSGL-1 Is Critical for Enterovirus 71 Infection

Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease, a common febrile disease in children; however, EV71 has been also associated with various neurological diseases including fatal cases in large EV71 outbreaks particularly in the Asia Pacific region. Recently we identified human P-selectin glycoprotein ligand-1 (PSGL-1) as a cellular receptor for entry and replication of EV71 in leukocytes. PSGL-1 is a sialomucin expressed on the surface of leukocytes, serves as a high affinity counterreceptor for selectins, and mediates leukocyte rolling on the endothelium. The PSGL-1–P-selectin interaction requires sulfation of at least one of three clustered tyrosines and an adjacent O-glycan expressing sialyl Lewis x in an N-terminal region of PSGL-1. To elucidate the molecular basis of the PSGL-1–EV71 interaction, we generated a series of PSGL-1 mutants and identified the post-translational modifications that are critical for binding of PSGL-1 to EV71. We expressed the PSGL-1 mutants in 293T cells and the transfected cells were assayed for their abilities to bind to EV71 by flow cytometry. We found that O-glycosylation on T57, which is critical for PSGL-1–selectin interaction, is not necessary for PSGL-1 binding to EV71. On the other hand, site-directed mutagenesis at one or more potential tyrosine sulfation sites in the N-terminal region of PSGL-1 significantly impaired PSGL-1 binding to EV71. Furthermore, an inhibitor of sulfation, sodium chlorate, blocked the PSGL-1–EV71 interaction and inhibited PSGL-1-mediated viral replication of EV71 in Jurkat T cells in a dose-dependent manner. Thus, the results presented in this study reveal that tyrosine sulfation, but not O-glycosylation, in the N-terminal region of PSGL-1 may facilitate virus entry and replication of EV71 in leukocytes

Tyrosine Sulfation of Native Mouse Psgl-1 Is Required for Optimal Leukocyte Rolling on P-Selectin In Vivo

We recently demonstrated that tyrosine sulfation is an important contributor to monocyte recruitment and retention in a mouse model of atherosclerosis. P-selectin glycoprotein ligand-1 (Psgl-1) is tyrosine-sulfated in mouse monocyte/macrophages and its interaction with P-selectin is important in monocyte recruitment in atherosclerosis. However, whether tyrosine sulfation is required for the P-selectin binding function of mouse Psgl-1 is unknown. Here we test the function of native Psgl-1 expressed in leukocytes lacking endogenous tyrosylprotein sulfotransferase (TPST) activity.Psgl-1 function was assessed by examining P-selectin dependent leukocyte rolling in post-capillary venules of C57BL6 mice transplanted with hematopoietic progenitors from wild type (WT → B6) or Tpst1;Tpst2 double knockout mice (Tpst DKO → B6) which lack TPST activity. We observed that rolling flux fractions were lower and leukocyte rolling velocities were higher in Tpst DKO → B6 venules compared to WT → B6 venules. Similar results were observed on immobilized P-selectin in vitro. Finally, Tpst DKO leukocytes bound less P-selectin than wild type leukocytes despite equivalent surface expression of Psgl-1.These findings provide direct and convincing evidence that tyrosine sulfation is required for optimal function of mouse Psgl-1 in vivo and suggests that tyrosine sulfation of Psgl-1 contributes to the development of atherosclerosis

A pipeline for high throughput detection and mapping of SNPs from EST databases

Single nucleotide polymorphisms (SNPs) represent the most abundant type of genetic variation that can be used as molecular markers. The SNPs that are hidden in sequence databases can be unlocked using bioinformatic tools. For efficient application of these SNPs, the sequence set should be error-free as much as possible, targeting single loci and suitable for the SNP scoring platform of choice. We have developed a pipeline to effectively mine SNPs from public EST databases with or without quality information using QualitySNP software, select reliable SNP and prepare the loci for analysis on the Illumina GoldenGate genotyping platform. The applicability of the pipeline was demonstrated using publicly available potato EST data, genotyping individuals from two diploid mapping populations and subsequently mapping the SNP markers (putative genes) in both populations. Over 7000 reliable SNPs were identified that met the criteria for genotyping on the GoldenGate platform. Of the 384 SNPs on the SNP array approximately 12% dropped out. For the two potato mapping populations 165 and 185 SNPs segregating SNP loci could be mapped on the respective genetic maps, illustrating the effectiveness of our pipeline for SNP selection and validation

Competitive Asymmetries in the Use of Supplementary Food by the Endangered Iberian Lynx (Lynx pardinus)

Background: As a conservation tool, supplementary feeding programs may be directed to specific individuals or sectors of the target population whose productivity or survival is thought to be limited by food scarcity. However, the use of supplemental food by different sex and age classes has received little attention. We studied individual variation in the access of the endangered Iberian lynx (Lynx pardinus) to supplementary food. Methodology/Principal Findings: From 5349 pictures taken with automatic cameras placed in 25 feeding stations, we identified 28 individuals whose sex and age were known. All individuals known to live in areas subjected to supplementation regularly visited feeding stations. Food consumption was not proportional to expected variations in energy demand within sex and age classes. Food consumption by males was higher than by females, and increased with age, in agreement with a despotic distribution. Food consumption also increased with lynx body mass, and this pattern held for individuals sharing the same breeding territories. The access of inferior competitors increased with the number of feeding stations available within lynx territories. Conclusions/Significance: All lynx exposed to food supplementation made a regular use of extra food but individuals predicted to be competitively dominant visited stations more frequently than subordinates of the same breeding territory. Our results suggest that insufficient provision of supplementary food could restrict the access of juveniles, or even adult females, to feeding stations. Limited consumption by these target individuals may compromise the efficiency of the supplementary feeding programme at the population level, in endangered species that, as the Iberian lynx, exhibit marked sexual dimorphism in body size.Peer reviewe

The Influence of Reproductive Experience on Milk Energy Output and Lactation Performance in the Grey Seal (Halichoerus grypus)

Although evidence from domestic and laboratory species suggests that reproductive experience plays a critical role in the development of aspects of lactation performance, whether reproductive experience may have a significant influence on milk energy transfer to neonates in wild populations has not been directly investigated. We compared maternal energy expenditures and pup growth and energy deposition over the course of lactation between primiparous and fully-grown, multiparous grey seal (Halichoerus grypus) females to test whether reproductive experience has a significant influence on lactation performance. Although there was no difference between primiparous females in milk composition and, thus, milk energy content at either early or peak lactation primiparous females had a significantly lower daily milk energy output than multiparous females indicating a reduced physiological capacity for milk secretion