Outcomes of bilateral axillo-breast approach robotic parathyroidectomy versus open parathyroidectomy for primary hyperparathyroidism: a single-institution retrospective study.

Purpose: Bilateral axillo-breast approach robotic parathyroidectomy (BABA-RP) aims to remove overactive or enlarged parathyroid glands with no visible neck collar incision. In this study, we compared the safety and surgical outcomes of BABA-RP vs. those of an open surgery group to ascertain whether BABA-RP is a safe and feasible surgical approach for patients with primary hyperparathyroidism (pHPT). Methods: This single-institution retrospective cohort study included 74 patients with primary HPT who underwent open parathyroidectomy (n = 37) or BABA-RP (n = 37) at our institution between November 2014 and March 2023. Patient demographics, biochemical cure rates, operative time, blood loss rates, and complication rates were examined and compared. Results: The patients in the BABA-RP group were younger and had a longer mean operative time. Regarding complication events, 2 patients in the open surgery group and 1 patient in the BABA-RP group had transient hypoparathyroidism. All 74 patients achieved biochemical cure at <6 months, regardless of the approach used. Two patients in the BABA-RP group and 1 patient in the open surgery group had carcinoma on surgical pathology. All 3 patients with parathyroid carcinoma remained recurrence-free at 1-year follow-up. Conclusion: Compared with the open procedure, BABA-RP is a safe and feasible procedure that provides an excellent biochemical cure rate for patients with pHPT and has superior cosmetic benefits with equivalent surgical outcomes.

TSH receptor antibody as a predictor of difficult robotic thyroidectomy in patients with Graves' disease.

Thyroidectomy in Graves' disease can be challenging due to greater thyroid size and vascularity. While thyroid stimulating hormone receptor antibody (TRAb) level is associated with disease severity and thyroid vascularity, its impact on operative outcomes remains unclear. This study aimed to compare challenging factors for robotic thyroidectomy (RT) and open thyroidectomy (OT) in Graves' disease patients, including TRAb as a predictive factor for difficult thyroidectomy. This retrospective study included Graves' disease patients who underwent total thyroidectomy between September 2013 and January 2023. The clinical characteristics and operative outcomes were compared between patients who received OT and bilateral axillo-breast approach RT. Factors affecting operation time and estimated blood loss (EBL) were evaluated in both groups using regression analyses. A total of 85 patients received either OT (n = 48) or RT (n = 37). Median thyroid volumes in the OT and RT groups were 72.4 g and 57.6 g, respectively. Operation time was affected by thyroid volume in both groups. Additionally, higher thyroid hormone levels and bilateral central neck node dissection prolonged operation time in the RT group. EBL was marginally associated with thyroid volume in the OT group. However, in the RT group, TRAb level was independently associated with greater EBL (p = 0.04), while no significant association was found with thyroid volume. Predictive factors for difficult thyroidectomy differed by operation approaches. TRAb significantly predicted intraoperative bleeding in RT, while this association was absent in OT. Caution is warranted when performing RT on Graves' disease patients with high TRAb levels.

Omega-Class Glutathione Transferases Protect DNA from Oxidative Stress in Pathogenic Helminth Reproductive Cells.

Pathogenic helminths have evolved mechanisms to preserve reproductive function while surviving long-term in the host via robust protective responses. A protective role of antioxidant enzymes in preventing DNA degradation has long been proposed, but little evidence has been provided. Here, we show that omega-class glutathione transferases (GSTOs) are critical for maintaining viability by protecting the reproductive cell DNA of the carcinogenic liver fluke, Clonorchis sinensis. Clonorchis sinensis GSTO (CsGSTO) activities modified by changes in the GSH/GSSG and NADPH/NADP+ molar ratios suppressed the overproduction of reactive oxygen species. CsGSTO1 and CsGSTO2 catalyzed deglutathionylation under physiologic and low-stress conditions (GSH/GSSG ratio of 6:1 or higher) but promoted glutathionylation under high-stress conditions (GSH/GSSG ratio of 3:1 or lower). Gliotoxin-induced functional disruption of CsGSTOs in living C. sinensis reduced the GSH/GSSG molar ratio and increased the production of protein glutathionylation (PSSG) under physiologic and low-stress conditions, indicating that suppression of GSTO function did not affect deglutathionylation. However, the perturbation of CsGSTOs decreased the GSH/GSSG ratio but also reduced PSSG production under high oxidative stress, demonstrating that glutathionylation was impeded. In response to oxidative stimuli, C. sinensis decreased GSTO-specific dehydroascorbate reductase and thiol transferase activities and the GSH/GSSG ratio, while it increased the NADPH/NADP+ ratio and PSSG. CsGSTOs utilized GSH to regulate GSH/GSSG and NADPH/NADP+ recycling and triggered a redox signal leading to nuclear translocation. Nuclear-imported CsGSTOs were modified by glutathionylation to prevent DNA damage. Antibodies specific to CsGSTOs dose-dependently inhibited this process. Disruption of CsGSTOs or the depletion of GSH caused glutathionylation defects, leading to DNA degradation. Our results demonstrate that CsGSTOs and the GSH system play a previously unappreciated role in protecting DNA from oxidative stress.

Echinococcus granulosus Protoscolex DM9 Protein Shows High Potential for Serodiagnosis of Alveolar Echinococcosis.

Alveolar echinococcosis (AE) caused by infection with E. multilocularis metacestode, represents one of the most fatal helminthic diseases. AE is principally manifested with infiltrative, proliferating hepatic mass, resembling primary hepatocellular carcinoma. Sometimes metastatic lesions are found in nearby or remote tissue. AE diagnosis largely depends on imaging studies, but atypical findings of imaging features frequently require differential diagnosis from other hepatic lesions. Serological tests may provide further evidence, while obtaining reliable AE materials is not easy. In this study, alternative antigens, specific to AE were identified by analyzing E. granulosus protoscolex proteins. An immunoblot analysis of E. granulosus protoscolex showed that a group of low-molecular-weight proteins in the range from 14 kDa to 16 kDa exhibited a sensitive and specific immune response to AE patient sera. Partial purification and proteomic analysis indicated that this protein group contained myosin, tubulin polymerization promoting protein, fatty-acid binding protein, uncharacterized DM9, heat shock protein 90 cochaperone tebp P-23, and antigen S. When the serological applicability of recombinant forms of these proteins was assessed using enzyme-linked immunosorbent assay, DM9 protein (rEgDM9) showed 90.1% sensitivity (73/81 sera tested) and 94.5% specificity (172/181 sera tested), respectively. rEgDM9 showed weak cross-reactions with patient sera from the transitional and chronic stages of cystic echinococcosis (3 to 5 stages). rEgDM9 would serve as a useful alternative antigen for serodiagnosis of both early- and advanced-stage AE cases.

Cerebral paragonimiasis: Clinicoradiological features and serodiagnosis using recombinant yolk ferritin.

Cerebral paragonimiasis (CP), caused by aberrant migration of Paragonimus worms, frequently invokes serious illness. The causal relationship between the lesion characteristics and patients' symptoms has poorly been understood. CP serodiagnosis has not been properly evaluated to date. A total of 111 CP cases were diagnosed in our laboratory between 1982 and 2003. This study retrospectively assessed the clinical and imaging characteristics of the 105 patients along with the evaluation of diagnostic potentials of recombinant P. westermani yolk ferritin (rPwYF) by enzyme-linked immunosorbent assay (ELISA) employing patients' sera and cerebrospinal fluids (CSFs). We analyzed 60 male and 45 female patients; 50 early-stage patients with non-calcified enhancing nodule(s) (median age, 38 years; interquartile range [IQR], 24.75-52; median symptom duration, 0.75 years; IQR, 0.2-2) and 54 chronic cases having calcified lesion(s) (median age, 33 years; IQR, 25-41; median symptom duration, 10 years; IQR, 5-20). One patient showed a normal neuroimage. The patients were largely diagnosed in their 30s. The parietal lobe was most commonly affected, followed by occipital, frontal, and temporal lobes. Twenty-six patients had lesions encompassing ≥ two lobes. The patients complained mainly of seizures, headaches, hemiparesis, and focal neurologic deficits (P < 0.001). Seizures and visual defects were predominant in patients with calcified lesion(s) (P < 0.001). The diagnostic sensitivity and specificity of rPwYF against serum/CSF were 100%/97% and 97.2%/92.5%, respectively. The specific IgG antibody levels against rPwYF in sera and CSFs showed a positive correlation (r = 0.59). The clinical manifestations of the early-stage patients might be associated with cortical lesions or meningeal irritation, while those in the chronic stage were caused by conglomerated space-occupying lesions. rPwYF would be useful for the serodiagnosis of both early and chronic CP cases.

Omega-Class Glutathione Transferases of Carcinogenic Liver Fluke, Clonorchis sinensis, Modulate Apoptosis and Differentiation of Host Cholangiocytes.

The small liver fluke Clonorchis sinensis causes hepatobiliary ductal infections in humans. Clonorchiasis is characterized histopathologically by ductal dysplasia, hyperplasia and metaplasia, which closely resembles cholangiocarcinoma (CCA). The disruption of programmed cell death is critical for malignant transformation, while molecular events underlying these phenomena have poorly been understood in clonorchiasis-related CCA tumorigenesis. We incorporated recombinant C. sinensis omega-class glutathione transferase (rCsGSTo) 1 or 2 into human intrahepatic biliary epithelial cells (HIBECs) and analyzed pathophysiological alterations of HIBECs upon the application of oxidative stress. rCsGSTos partially but significantly rescued HIBECs from cell death by inhibiting oxidative stress-induced apoptosis (p < 0.01). rCsGSTos modulated transcriptional levels of numerous genes. We analyzed 13 genes involved in programmed cell death (the upregulation of five antiapoptotic and two apoptotic genes, and the downregulation of one antiapoptotic and five apoptotic genes) and 11 genes associated with cell differentiation (the increase in seven and decrease in four genes) that showed significant modifications (p < 0.05). The induction profiles of the mRNA and proteins of these differentially regulated genes correlated well with each other, and mostly favored apoptotic suppression and/or cell differentiation. We detected increased active, phosphorylated forms of Src, PI3K/Akt, NF-κB p65, MKK3/6 and p38 MAPK, but not JNK and ERK1/2. CsGSTos were localized in the C. sinensis-infected rat cholangiocytes, where cytokeratin 19 was distributed. Our results demonstrated that CsGSTos excreted to the biliary lumen are internalized and accumulated in the host cholangiocytes. When cholangiocytes underwent oxidative stressful condition, CsGSTos appeared to be critically involved in both antiapoptotic process and the differentiation of host cholangiocytes through the regulation of target genes following the activation of responsible signal molecules.

Spectrum of pleuropulmonary paragonimiasis: An analysis of 685 cases diagnosed over 22 years.

OBJECTIVES: Paragonimiasis is a global foodborne zoonosis. Overlapping clinical and imaging features with other lung pathologies hamper correct diagnosis and require differential diagnosis. METHODS: During 1982-2003, 49,012 samples were referred for immunodiagnosis of helminthiases. We detected paragonimiasis cases by enzyme-linked immunosorbent assay (ELISA). We assessed clinical, radiographical and laboratory characteristics, and diagnostic dilemmas associated with delayed diagnosis. RESULTS: We analyzed 685 pleuropulmonary paragonimiasis cases. ELISA-positive was 665. Eggs were detected in 50. Symptom duration correlated well with the appearance of chest radiographs; 359 pleural, 33 pleuroparenchymal, and 264 parenchymal lesions (P < 0.001). Twenty-nine had normal chest images. Eosinophilia, seen in 304, was common in pleural and pleuroparenchymal patients (P < 0.05). Chest pain and dyspnea were characteristic for pleurisy patients. Sputum (odds ratios [OR]: 6.79; 95% CI: 4.41-10.47), blood-tinged sputum (OR: 5.62; 95% CI: 3.75-8.42), and foul-odor (OR: 2.70; 95% CI: 1.42-5.16) were significant in parenchymal patients. Delayed diagnosis (119) for ≥ 25 weeks was attributed mainly to misdiagnosis as tuberculosis, malignancy, or chronic obstructive pulmonary disease (COPD) (OR: 111.75; 95% CI: 43.25-288.74). CONCLUSIONS: Variable symptoms and radiographs of pleuropulmonary paragonimiasis depended on the stage of infection. Suspicion of tuberculosis, malignancy, or COPD was major cause of delayed diagnosis.

Survey of echinococcoses in southeastern Qinghai Province, China, and serodiagnostic insights of recombinant Echinococcus granulosus antigen B isoforms.

BACKGROUND: Echinococcoses, caused by metacestodes of Echinococcus granulosus (cystic echinococcosis; CE) and E. multilocularis (alveolar echinococcosis; AE), represent major emerging parasitic diseases. These enzootic helminthiases invoke significant public health concerns and social burdens in endemic areas. The diseases are prevalent in the Qinghai-Tibetan Plateau, China, while community-based epidemiological studies have been scarcely reported. We surveyed echinococcosis patients in the southeastern Qinghai Province, China, to better understand the concurrent epidemiological situation in this area. METHODS: During July and August of 2013 and 2014, we screened echinococcosis patients at Yushu and Golog Prefectures, Qinghai Province, China, in a diagnostic campaign. A total of 2856 people (male:female ratio, 1:1.12; mean age, 34.6 years; age range, 6-88 years) were ultrasonographically examined for the presence of hepatic echinococcal cysts. We also collected serum samples from patients and analyzed antibody reactivity against recombinant forms of diverse E. granulosus antigen Bs (rEgAgB1-5) by enzyme-linked immunosorbent assay. RESULTS: We detected 134 patients whose imaging scans were compatible with CE (115 cases) and AE (20 patients). One patient might have been infected with both CE and AE. The overall incidence was 4.7% (CE, 4.0%; AE, 0.7%). A large proportion (67.5%) of CE patients was diagnosed at active and transitional CE1-CE3 stages in their late 30s. The AE cases were generally detected at advanced stage in patients at early 20s (60%). Analysis of the receiver operating characteristic curve and Youden's index indicated that rEgAgB2 was the most promising biomarker, followed by rEgAgB3 and rEgAgB1. Overall, sensitivity and specificity of rEgAgB1-3 were 84.5-92.7% and 91.9-94.6%, respectively. rEgAgB4 and 5 showed low sensitivity with high cross-reactivity. CONCLUSIONS: Our results strongly suggest that disability-adjusted life years related to echinococcoses in Qinghai-Tibetan areas might be more serious than previously considered. Control and prevention strategy against CE and AE are highly required in these areas. In addition to ultrasonography, serological tests might provide supportive data. However, serological data should be carefully interpreted for differential diagnosis, especially in areas where both CE and AE are co-endemic.

Advances in Serological Diagnosis of Taenia solium Neurocysticercosis in Korea.

Cysticercosis, a parasitic disease caused by Taenia solium metacestode (TsM), has a major global public health impact in terms of disability-adjusted life years. The parasite preferentially infects subcutaneous tissue, but may invade the central nervous system, resulting in neurocysticercosis (NC). NC is an important neglected tropical disease and an emerging disease in industrialized countries due to immigration from endemic areas. The prevalence of taeniasis in Korea declined from 0.3%-12.7% during the 1970s to below 0.02% since the 2000s. A survey conducted from 1993 to 2006 revealed that the percentage of tested samples with high levels of specific anti-TsM antibody declined from 8.3% to 2.2%, suggesting the continuing occurrence of NC in Korea. Modern imaging modalities have substantially improved the diagnostic accuracy of NC, and recent advances in the molecular biochemical characterization of the TsM cyst fluid proteome also significantly strengthened NC serodiagnosis. Two glycoproteins of 150 and 120 kDa that induce strong antibody responses against sera from patients with active-stage NC have been elucidated. The 150 kDa protein showed hydrophobic-ligand binding activities and might be critically involved in the acquisition of host-derived lipid molecules. Fasciclin and endophilin B1, both of which play roles in the homeostatic functions of TsM, showed fairly high antibody responses against calcified NC cases. NC is now controllable and manageable. Further studies should focus on controlling late-onset intractable seizures and serological diagnosis of NC patients infected with few worms. This article briefly overviews diagnostic approaches and discusses current issues relating to NC serodiagnosis.

Human Sparganosis in Korea.

BACKGROUND: Sparganosis is a larval cestodiasis caused by the plerocercoid of Spirometra spp. Since the first description of human sparganosis in 1924, several hundred cases have been reported in Korea. However, systematic approaches for literature surveys of Korean sparganosis have seldom appeared. METHODS: We searched publicly available databases such as PubMed, Research Information Sharing Service, and Korea Medical Citation Index with relevant Medical Subject Headings. RESULTS: At least 438 Korean sparganosis cases have been described from 1924 to 2015. Preoperative diagnosis has been significantly increased since the 1980s due to popularization of serological and imaging diagnostics. Cases were largely detected from fifth decades in general, but cerebral sparganosis was detected in relatively young age groups (third and fourth decades). Sparganosis was prevalent in men (75.9%). Consumption of frog/snake and drinking unfiltered water were found in 63.4% and 16.9% of patients, respectively. Most frequently affected sites were subcutaneous tissues (49.9%), followed by the central nervous system (36.2%). Involvements of visceral organs (7.6%), ocular regions (3.6%), and muscles (2.7%) were noticed. In women, breast sparganosis constituted a large proportion (34.2%). Sparganosis associated with immunocompromised patients has recently been reported. CONCLUSION: Sparganosis has been continuously reported in Korea during the past 90 years, although its incidence has decreased during the last 20 years. The disease is mostly characterized by subcutaneous nodule, but infection of the worm in vital organs often results in serious illness. Continuous awareness is warranted to monitor sparganosis occurrence and associated clinical consequences.

Comparison of Secretome Profile of Pathogenic and Non-Pathogenic Entamoeba histolytica.

The obligatory intracellular protozoan parasite Entamoeba histolytica causes amebic dysentery and liver abscess. E. histolytica adheres to the host tissues in a contact-dependent manner. E. histolytica excretory-secretory products (ESP) might play critical roles during invasion. We comparatively analyzed the secretome profile of E. histolytica pathogenic HM-1:IMSS and non-pathogenic Rahman strains. The two ESP revealed similar but distinct spotting patterns. In both ESP, alcohol dehydrogenase, enolase 1, and transketolase, which control classical carbohydrate metabolism and other moonlighting effects, constituted the most abundant fractions. We recognized differently secreted molecules. Secretion of cytoskeletal organization proteins (actin, actin binding protein, and EHI_068510), protein remodeling amino peptidase, and multifunctional elongation factor 1-α were increased in Rahman. Conversely, carbohydrate metabolizing enolase 1, alcohol dehydrogenase, transketolase, calponin, phosphoglucose mutase, malic enzyme and EHI_156420, xenobiotic scavenging superoxide dismutase and EHI_140740, and pyruvate:ferredoxin oxidoreductase and coronin (carbohydrate metabolism/detoxification) showed reduced secretion. Transcription levels of some genes involved in these processes also decreased. Changes of secretory behavior, especially decreased secretion of multifunctional carbohydrate metabolizing enzymes and detoxifying proteins that importantly participated in amoeba pathogenesis might reflect avirulent nature of Rahman strain in the host.

Comparison of Echinococcus multilocularis and Echinococcus granulosus hydatid fluid proteome provides molecular strategies for specialized host-parasite interactions.

Alveolar and cystic echinococcoses, caused by the metacestodes of Echinococcus multilocularis and E. granulosus, are prevalent in several regions and invoke deleterious zoonotic helminthiases. Hydatid fluid (HF), which contains proteinaceous and non-proteinaceous secretions of the parasite- and host-derived components, critically affects the host-parasite interplay and disease progression. We conducted HF proteome profiling of fully mature E. multilocularis vesicle (nine months postinfection) and E. granulosus cyst (stage 2). We identified 120 and 153 proteins, respectively, in each fluid. Fifty-six and 84 proteins represented distinct species; 44 and 66 were parasites, and 12 and 18 were host-derived proteins. The five major parasite protein populations, which included antigen B isoforms, metabolic enzymes, proteases and inhibitors, extracellular matrix molecules (ECMs), and developmental proteins, were abundantly distributed in both fluids and also exclusively in one sample or the other. Carbohydrate-metabolizing enzymes were enriched in E. granulosus HF. In the E. multilocularis HF, proteins that constitute ECMs, which might facilitate adhesion and cytogenesis, were highly expressed. Those molecules had physical and functional relationships along with their biochemical properties through protein-protein interaction networks. Twelve host-derived proteins were largely segregated to serum components. The major proteins commonly and uniquely detected in these HFs and their symbiotic interactome relationships might reflect their biological roles in similar but distinct modes of maturation, invasion, and the longevity of the parasites in the hosts.

Fasciclin-calcareous corpuscle binary complex mediated protein-protein interactions in Taenia solium metacestode.

BACKGROUND: Neurocysticercosis (NC) caused by Taenia solium metacestode (TsM) is a serious neurological disease of global concern. Diverse bioactive molecules involved in the long-term survival of TsM might contribute to disease progression. Fasciclin (Fas) is an extracellular protein that mediates adhesion, migration and differentiation of cells by interacting with other molecules. We hypothesized that TsMFas might bind to calcareous corpuscle (CC) through its adhesive property and participate in crucial protein-protein interactions, thus contributing to the creation of a symbiotic interactome network. METHODS: Two paralogous TsMFas (TsMFas1 and TsMFas2) were isolated, and their molecular properties were characterized. The co-localization pattern of TsMFas1 and TsMFas2 with CC was determined. CC-TsMFas binary complex was generated by incubating CC with recombinant proteins (rTsMFas1 and 2). In vitro binding assay of CC-rTsMFas1 or CC-rTsMFas2 binary complex with TsM cellular proteins extracted from scolex and neck was conducted. Their binding partners were identified through proteomic analysis. Integrated protein-protein interaction networks were established. RESULTS: TsMFas1 (6072 bp long) was composed of 15 exons (841 amino acid polypeptide) interrupted by 14 introns. TsMFas2 (5201 bp long) comprised of 11 exons (597 amino acids) and 10 intervening introns. These proteins displayed 22% amino acid sequence identity to each other, but tightly conserved Fas-related domains. Several isoforms of Fas1 and Fas2 proteins might have been expressed through post-translational modifications. They showed adhesion activity with other cells. TsMFas proteins were largely distributed in parenchymal regions of the scolex and bladder wall. These molecules were co-localized with CC, a unique organelle found in platyhelminths. Subsequent proteome analysis of CC-Fas binary complex mediated protein-protein interactions revealed seven protein ligands in the TsM cellular proteins. Their functions were mainly segregated into carbohydrate metabolism (enolase, phosphoenolpyruvate carboxykinase, phosphoglycerate kinase and glyceraldehyde 3-phosphate dehydrogenase) and cytoskeleton/cellular motility (actin, paramyosin and innexin nuc-9). Those proteins had direct (physical) and/or indirect (functional) relationships along with their biochemical properties and biological roles. CONCLUSION: Protein repertoires strongly suggest that TsMFas and CC may symbiotically mediate protein-protein interactions during biological processes to maintain efficacious homeostatic functions and ensure the prolonged survival of TsM in the host.

Recurrent emergence of structural variants of LTR retrotransposon CsRn1 evolving novel expression strategy and their selective expansion in a carcinogenic liver fluke, Clonorchis sinensis.

Autonomous retrotransposons, in which replication and transcription are coupled, encode the essential gag and pol genes as a fusion or separate overlapping form(s) that are expressed in single transcripts regulated by a common upstream promoter. The element-specific expression strategies have driven development of relevant translational recoding mechanisms including ribosomal frameshifting to satisfy the protein stoichiometry critical for the assembly of infectious virus-like particles. Retrotransposons with different recoding strategies exhibit a mosaic distribution pattern across the diverse families of reverse transcribing elements, even though their respective distributions are substantially skewed towards certain family groups. However, only a few investigations to date have focused on the emergence of retrotransposons evolving novel expression strategy and causal genetic drivers of the structural variants. In this study, the bulk of genomic and transcribed sequences of a Ty3/gypsy-like CsRn1 retrotransposon in Clonorchis sinensis were analyzed for the comprehensive examination of its expression strategy. Our results demonstrated that structural variants with single open reading frame (ORF) have recurrently emerged from precedential CsRn1 copies encoding overlapping gag-pol ORFs by a single-nucleotide insertion in an upstream region of gag stop codon. In the parasite genome, some of the newly evolved variants appeared to undergo proliferative burst as active master lineages together with their ancestral copies. The genetic event was similarly observed in Opisthorchis viverrini, the closest neighbor of C. sinensis, whereas the resulting structural variants might have failed to overcome purifying selection and comprised minor remnant copies in the Opisthorchis genome.

Hed1 Promotes Meiotic Crossover Formation in Saccharomyces cerevisiae.

Homologous recombination occurs between homologous chromosomes and is significantly involved in programmed double-strand break (DSB) repair. Activation of two recombinases, Rad51 and Dmc1, is essential for an interhomolog bias during meiosis. Rad51 participates in both mitotic and meiotic recombination, and its strand exchange activity is regulated by an inhibitory factor during meiosis. Thus, activities of Rad51 and Dmc1 are coordinated to promote homolog bias. It has been reported that Hed1, a meiosis-specific protein in budding yeast, regulates Rad51-dependent recombination activity. Here, we investigated the role of Hed1 in meiotic recombination by ectopic expression of the protein after pre-meiotic replication in Saccharomyces cerevisiae. DNA physical analysis revealed that the overexpression of Hed1 delays the DSB-to-joint molecule (JM) transition and promotes interhomolog JM formation. The study indicates a possible role of Hed1 in controlling the strand exchange activity of Rad51 and, eventually, meiotic crossover formation.

Biochemical Characterization of Echinococcus multilocularis Antigen B3 Reveals Insight into Adaptation and Maintenance of Parasitic Homeostasis at the Host-Parasite Interface.

Alveolar echinococcosis (AE) caused by Echinococcus multilocularis metacestode is frequently associated with deleterious zoonotic helminthiasis. The growth patterns and morphological features of AE, such as invasion of the liver parenchyme and multiplication into multivesiculated masses, are similar to those of malignant tumors. AE has been increasingly detected in several regions of Europe, North America, Central Asia, and northwestern China. An isoform of E. multilocularis antigen B3 (EmAgB3) shows a specific immunoreactivity against patient sera of active-stage AE, suggesting that EmAgB3 might play important roles during adaptation of the parasite to hosts. However, expression patterns and biochemical properties of EmAgB3 remained elusive. The protein profile and nature of component proteins of E. multilocularis hydatid fluid (EmHF) have never been addressed. In this study, we conducted proteome analysis of EmHF of AE cysts harvested from immunocompetent mice. We observed the molecular and biochemical properties of EmAgB3, including differential transcription patterns of paralogous genes, macromolecular protein status by self-assembly, distinct oligomeric states according to individual anatomical compartments of the worm, and hydrophobic ligand-binding protein activity. We also demonstrated tissue expression patterns of EmAgB3 transcript and protein. EmAgB3 might participate in immune response and recruitment of essential host lipids at the host-parasite interface. Our results might contribute to an in depth understanding of the biophysical and biological features of EmAgB3, thus providing insights into the design of novel targets to control AE.

Spatiotemporal Expression Patterns and Antibody Reactivity of Taeniidae Endophilin B1.

Larval Taeniidae, such as metacestodes of Taenia solium, Echinococcus granulosus, and Echinococcus multilocularis, produce chronic and fatal helminthic diseases. Proper identification of these zoonotic cestodiases is often challenging and is hampered in some clinical settings. Endophilin B1 plays critical roles in the maintenance of membrane contours and endocytosis. We isolated proteins homologous to endophilin B1 from T. solium, Taenia saginata, and Taenia asiatica The three Taeniidae endophilin B1 proteins shared 92.9 to 96.6% sequence identity. They harbored a Bin1/amphiphysin/Rvs (BAR) domain and residues for a dimeric interface but lacked a SRC homology 3 (SH3) domain. Endophilin B1 showed a unique immunological profile and was abundantly expressed in the tegumental syncytium of Taeniidae metacestodes and adults. Bacterially expressed recombinant T. solium endophilin B1 (rTsMEndoB1) demonstrated a sensitivity of 79.7% (345/433 cases) for serodiagnosis of larval Taeniidae infections. The protein showed strong immune recognition patterns against sera from patients with chronic neurocysticercosis, cystic echinococcosis, or advanced-stage alveolar echinococcosis. Adult Taeniidae infections exhibited moderate degrees of positive antibody responses (65.7% [23/35 samples]). rTsMEndoB1 showed some cross-reactivity with sera from patients infected with Diphyllobothriidae (23.6% [25/106 samples]) but not with sera from patients with other parasitic diseases or normal controls. The specificity was 91.7% (256/301 samples). The positive and negative predictive values were 93.6% and 73.4%, respectively. Our results demonstrate that Taeniidae endophilin B1 may be involved in the control of membrane dynamics, thus contributing to shaping and maintaining the tegumental curvature. rTsMEndoB1 may be useful for large-scale screening, as well as for individual diagnosis and follow-up surveillance of Taeniidae infections.