Sample records for syn capillaria plica

  1. Pearsonema (syn Capillaria) plica associated cystitis in a Fennoscandian arctic fox (Vulpes lagopus: a case report

    PubMed Central

    2010-01-01

    The bladderworm Pearsonema (syn Capillaria) plica affects domestic dogs and wild carnivores worldwide. A high prevalence in red foxes (Vulpes vulpes) has been reported in many European countries. P. plica inhabits the lower urinary tract and is considered to be of low pathogenic significance in dogs mostly causing asymptomatic infections. However, a higher level of pathogenicity has been reported in foxes. A severe cystitis associated with numerous bladderworms was found in a captive arctic fox (Vulpes lagopus) originating from the endangered Fennoscandian arctic fox population. To our knowledge this is the first description of P. plica infection in an arctic fox. PMID:20540788

  2. Pearsonema (syn Capillaria) plica associated cystitis in a Fennoscandian arctic fox (Vulpes lagopus: a case report.

    PubMed

    Fernández-Aguilar, Xavier; Mattsson, Roland; Meijer, Tomas; Osterman-Lind, Eva; Gavier-Widén, Dolores

    2010-06-12

    The bladderworm Pearsonema (syn Capillaria) plica affects domestic dogs and wild carnivores worldwide. A high prevalence in red foxes (Vulpes vulpes) has been reported in many European countries. P. plica inhabits the lower urinary tract and is considered to be of low pathogenic significance in dogs mostly causing asymptomatic infections. However, a higher level of pathogenicity has been reported in foxes. A severe cystitis associated with numerous bladderworms was found in a captive arctic fox (Vulpes lagopus) originating from the endangered Fennoscandian arctic fox population. To our knowledge this is the first description of P. plica infection in an arctic fox.

  3. Extraintestinal nematodes of the red fox Vulpes vulpes in north-west Italy.

    PubMed

    Magi, M; Guardone, L; Prati, M C; Mignone, W; Macchioni, F

    2015-07-01

    Extraintestinal nematodes of the red fox (Vulpes vulpes) are a wide group of parasites that infect wild and domestic carnivores and occasionally humans. Nematodes in the cardiopulmonary system, stomach, urinary apparatus and muscle tissue of 165 red foxes (Vulpes vulpes) from north-west Italy (Liguria and Piedmont) were investigated between 2009 and 2012. Of the cardiopulmonary nematodes, a high prevalence of Angiostrongylus vasorum and Eucoleus aerophilus (syn. Capillaria aerophila) was found, 78.2% and 41.8% respectively; Crenosoma vulpis (15.8%) and Filaroides spp. (4.8%) were also found. Spirocerca lupi (23.5%), Aonchotheca putorii (syn. Capillaria putorii) (8.6%) and Physaloptera spp. (2.5%) were detected in the stomach and Pearsonema plica (syn. Capillaria plica) (56.8%) in the bladder. Eucoleus boehmi (syn. Capillaria boehmi) was also detected in the nasal cavities of one of the two foxes examined. A coprological examination revealed eggs of E. aerophilus, A. putorii, S. lupi, Physaloptera spp. and eggs of intestinal parasites. Filarial worms were absent in all the 165 animals examined, nor was there evidence of Trichinella spp. in any of the foxes. The foxes were found to host a high prevalence of many species of extraintestinal nematodes. The prevalence of A. vasorum in foxes found in the present study is among the highest in Europe. In addition, to the best of our knowledge, E. boehmi and Filaroides spp. have never been reported before in this host in Italy.

  4. High prevalence of Eucoleus boehmi (syn. Capillaria boehmi) in foxes from western Austria.

    PubMed

    Hodžić, Adnan; Bruckschwaiger, Pia; Duscher, Georg Gerhard; Glawischnig, Walter; Fuehrer, Hans-Peter

    2016-08-01

    Eucoleus boehmi (syn. Capillaria boehmi) is a canine trichuroid nematode affecting the upper respiratory airways (i.e., nasal cavity and paranasal sinuses) of dogs, foxes, and wolves. In the past few years, reports in dogs and wild canids have increased from across Europe, but data on its occurrence and distribution in Austria is scanty. A total of 47 red foxes (Vulpes vulpes) from the two westernmost provinces (Tyrol and Vorarlberg) of Austria were therefore examined for the presence of E. boehmi at necropsy. Eggs and adult nematodes were identified morphologically and molecularly (cox1) as E. boehmi. These nematodes were found in 26 (78.8 %) and 13 (92.9 %) foxes from Tyrol and Vorarlberg, respectively, with an overall prevalence of 83.0 % (39/47). The prevalence rate of infection recorded in this study is among the highest in Europe. These results suggest that foxes may represent an important source of infection for dogs and other canids, but further studies are needed to elucidate the transmission dynamics.

  5. Morphological and molecular genetic characterization of three Capillaria spp. (Capillaria anatis, Capillaria pudendotecta, and Capillaria madseni) and Baruscapillaria obsignata (Nematoda: Trichuridae: Capillariinae) in avians.

    PubMed

    Tamaru, Masae; Yamaki, Seiya; Jimenez, Lea Angsinco; Sato, Hiroshi

    2015-11-01

    Morphological and genetic analyses were performed on four avian species of the subfamily Capillariinae (Nematoda: Trichuridae), i.e., Capillaria anatis from chickens (Gallus gallus domesticus) in Japan and the Philippines, Baruscapillaria obsignata from chickens and captive swans (Cygnus olor and Cygnus atratus) in Japan, Capillaria pudendotecta from captive swans in Japan, and Capillaria madseni from carrion and jungle crows (Corvus corone and Corvus macrorhynchos) in Japan. Although morphometric variations of male and female worms from different hosts and/or localities made the species identification difficult, the 18S ribosomal RNA gene (rDNA) sequences clarified their taxonomic position and phylogenetic relationships. Species of the same genus clustered robustly into a single clade in the phylogenetic tree based on the 18S rDNA, demonstrating to the extent possible the validity of the latest classification of the subfamily following Moravec's rearrangement in 1982. Male worms of C. pudendotecta are described here for the first time.

  6. Plica neuropathica (polonica) in schizophrenia

    PubMed Central

    Kumar, P. N. Suresh; Rajmohan, V.

    2012-01-01

    Plica neuropathica (Polonica) is a common but rarely reported scalp hair condition. In this condition the hairs of scalp in a localized area is compacted into irregularly twisted, irreversibly entangled plaits. Psychological disturbance is a risk factor for plica formation. We report a case of plica neuropathica in an adult female with schizophrenia. PMID:23226861

  7. Treerunners, cryptic lizards of the Plica plica group (Squamata, Sauria, Tropiduridae) of northern South America

    PubMed Central

    Murphy, John C.; Jowers, Michael J.

    2013-01-01

    Abstract The arboreal, Neotropical lizard Plica plica (Linnaeus, 1758) has been long considered a widespread species with a distribution east of the Andes. A preliminary examination of 101 specimens from about 28 locations mostly north of the Amazon suggests that Plica plica is a cryptic species complex with taxa that can be distinguished on the basis of the number of scale rows at mid-body; the arrangement, shape and ornamentation of scales on the snout; the number of lamellae on the fourth toe; the number of subocular plates; as well as other commonly used external morphological traits. The allopatric species discussed here are concordant with northern South American geography. Plica plica (Linnaeus, 1758) is associated with the Guiana Shield (Suriname, Guyana and Venezuela). A second species, P. caribeana sp. n. is associated with the Caribbean Coastal Range of Venezuela including Trinidad and Tobago. A third, distinctive species, P. rayi sp. n. is associated with the middle Orinoco at the eastern edge of the Guiana Shield. Two other species, P. kathleenae sp. n. and P. medemi sp. n., each based upon a single specimen, one from the Sierra Acarai Mountains of Guyana, and the other from southern Meta, Colombia are described. In addition to morphological analyses, we sequenced 12S and 16S rDNA gene fragments from one Plica plica from Trinidad to assess its relationship and taxonomy to other mainland Plica cf. plica. The results suggest Plica caribeana sp. n. likely diverged prior to the separation of Trinidad from northern Venezuela. Isolation in the Caribbean Coastal Range during its rapid uplift in the late Miocene, combined with a marine incursion into northern Venezuela may have contributed to their genetic divergence from other populations. PMID:24363569

  8. Extraintestinal nematode infections of red foxes (Vulpes vulpes) in Hungary.

    PubMed

    Sréter, T; Széll, Z; Marucci, G; Pozio, E; Varga, I

    2003-08-14

    A survey was carried out to investigate the prevalence and worm burden of extraintestinal nematodes in 100 red foxes (Vulpes vulpes) of Hungary. The overall prevalence of nematode infections of the respiratory tract was 76%. Eucoleus aerophilus (Capillaria aerophila) was the predominant species (66%), followed by Crenosoma vulpis (24%), Eucoleus (Capillaria) böhmi (8%) and Angiostrongylus vasorum (5%). Pearsonema (Capillaria) plica was found in 52% of the urinary bladders. In 3% of the foxes, Trichinella britovi was present in muscle samples. The high prevalence of lungworms and P. plica and the fox colonisation in urban areas may enhance the prevalence of these nematode infections in domestic dogs and cats, and the flow of T. britovi from the sylvatic cycle to the domestic cycle, enhancing the risk of infections in humans.

  9. Snapping plicae associated with radiocapitellar chondromalacia.

    PubMed

    Antuna, S A; O'Driscoll, S W

    2001-05-01

    Painful snapping of the elbow joint is usually attributed to intra-articular loose bodies, instability, or medial dislocation of the triceps muscle over the medial epicondyle. We report our experience with 14 patients who were treated arthroscopically for snapping elbow that was found to be caused by hypertrophic synovial folds associated with radiocapitellar chondromalacia. Case series. The records of 14 patients who were treated arthroscopically for painful snapping elbows caused by intra-articular plicae were reviewed. There were 6 women and 8 men with an average age of 36 years (range, 27 to 48 years). Nine patients had had some type of trauma to the joint. Four patients had been previously diagnosed with lateral epicondylitis and 5 with intra-articular loose bodies. The average time from initial onset of symptoms to treatment was 13 months (range, 8 to 36 months). Average follow-up was 24 months (range, 6 to 66 months). All patients complained of painful snapping in the posterolateral or anterolateral aspect of the elbow. The snapping occurred between 90 degrees and 110 degrees of flexion with the forearm in pronation. In 7 patients, the snapping was reproducible by passively flexing the pronated elbow, which we refer to as the flexion-pronation test. At the time of arthroscopic surgery, all patients had a thickened synovial plica that would snap back and forward over the radial head, usually associated with a chondromalacic area on the radial head. Twelve patients had complete relief of their snapping after surgery. One patient in whom there was associated posterolateral rotatory elbow instability did not improve. One patient became asymptomatic for 4 years but then had recurrence of her symptoms, which persisted despite 2 subsequent arthroscopies. The presence of synovial plicae in the radiocapitellar joint must be considered in the differential diagnosis of painful snapping elbow. Arthroscopy confirms the diagnosis and allows excision of the plica.

  10. [Trichoma (Plica polonica) - a contemporary case with a historical disease].

    PubMed

    Wolf, Florian; Scherr, Martin; Scherthöffer, Dirk; Bäuml, Josef; Förstl, Hans

    2008-01-01

    We describe a 62-year-old patient with a chronic delusional disorder who presented with severely matted hair ("plica polonica"). Until the late 19th century such dreadlocks were considered as cause, consequence and treatment of mental disease. The historical development of "plica polonica" is briefly reviewed as an example of early and once popular psychiatric disease concepts.

  11. Capillaria hepatica infection in black rats (Rattus rattus) on Diego Garcia, British Indian Ocean Territory.

    PubMed

    Berentsen, Are R; Vogt, Scott; Guzman, Antenor N; Vice, Daniel S; Pitt, William C; Shiels, Aaron B; Spraker, Terry R

    2015-03-01

    Rats (Rattus spp.) are among the most damaging invasive species worldwide. The accidental introduction of rats has caused significant detriment to native flora and fauna, crops, structures, and human livelihoods. Rats are vectors of disease and carriers of various zoonotic parasites. Capillaria hepatica (syn. Callodium hepaticum) is a parasitic nematode found primarily in rodents but is known to infect over 140 mammal species, including human beings and several species of domestic animals. In this case study, the presence of C. hepatica infection in black rats on Diego Garcia, British Indian Ocean Territory, is reported. Liver samples from 20 black rats (Rattus rattus) were collected during a concurrent population density estimation study. Histology revealed 15 (75%) of the rats sampled had a current or previous infection with C. hepatica. In addition, a larval cestode compatible in size and shape with Cysticercus fasciolaris, the larval stage of Taenia taeniaeformis of cats, was found in 3 (15%) of the rats sampled. The high prevalence of C. hepatica infection in rats on Diego Garcia has implications for human health given the high population density of rats found on the island. © 2015 The Author(s).

  12. Arthroscopic resection of humeroradial synovial plica for persistent lateral elbow pain.

    PubMed

    Rajeev, Aysha; Pooley, Joesph

    2015-04-01

    To review the outcome of 121 patients who underwent arthroscopic resection of a humeroradial synovial plica for persistent lateral elbow pain. 92 men and 29 women aged 24 to 56 (mean, 38) years with chronic lateral elbow pain underwent arthroscopic resection of a humeroradial synovial plica using a motorised soft tissue shaver, followed by intensive physiotherapy. The modified elbow score and range of motion were assessed, as were wound healing, infection, soft tissue swelling or effusion, tenderness, ligamentous instability, and motor strength. No patient had any ligamentous instability. 80 patients were pain-free at 3 months; only 3 patients were taking pain medication at 6 months. All patients had full pronation and supination; the mean range of motion was 3º to 135º of flexion. The mean modified elbow score at 12 months was 93.2 (range, 72-100). The percentages of patients with excellent, good, fair, and poor score were 70%, 17%, 8%, and 5% at 3 months, 74%, 20%, 3%, and 3% at 6 months, and 76%, 18%, 3%, and 3% at 12 months, respectively. A humeroradial synovial plica is one of the causes of chronic lateral elbow pain. Arthroscopic resection of the synovial plica followed by intensive physiotherapy achieved good outcome.

  13. Matrix metalloprotease-3 expression in the medial plica and pannus-like tissue in knees from patients with medial compartment osteoarthritis.

    PubMed

    Wang, Hwai-Shi; Kuo, Pei-Yin; Yang, Chih-Chang; Lyu, Shaw-Ruey

    2011-03-01

    The severity of cartilage degeneration is positively correlated with the severity of the pathologic change of medial plica. However, knowledge of the pathogenic mechanisms and the impact of plica on cartilage destruction is limited. The aim of the present study was therefore to investigate matrix metalloprotease-3 (MMP-3) expression in the plica isolated from patients with medial compartment osteoarthritis of the knee. Immunohistochemistry showed that MMP-3 was highly expressed in pannus-like tissue and the plica. Western blotting of culture supernatants showed that interleukin-1β (IL-1β) treatment induced MMP-3 release by cells isolated from pannus tissue or the plica. Furthermore, reverse transcriptase polymerase chain reaction and real-time polymerase chain reaction analysis showed that MMP-3 mRNA levels were increased after IL-1β treatment of the cultured cells. MMP-3 and IL-1β mRNAs were expressed in the plica and pannus-like tissue, with MMP-3 mRNA being expressed at significantly higher levels in the plica than in normal synovial membrane and highly expressed in the plica at different stages in osteoarthritis (OA) patients. Pannus-like tissue and the plica express IL-1β and MMP-3. Moreover, MMP-3 mRNA and protein expression in the plica may contribute to the pathogenesis of OA. © 2011 Blackwell Publishing Limited.

  14. SynGenics Optimization System (SynOptSys)

    NASA Technical Reports Server (NTRS)

    Ventresca, Carol; McMilan, Michelle L.; Globus, Stephanie

    2013-01-01

    The SynGenics Optimization System (SynOptSys) software application optimizes a product with respect to multiple, competing criteria using statistical Design of Experiments, Response-Surface Methodology, and the Desirability Optimization Methodology. The user is not required to be skilled in the underlying math; thus, SynOptSys can help designers and product developers overcome the barriers that prevent them from using powerful techniques to develop better pro ducts in a less costly manner. SynOpt-Sys is applicable to the design of any product or process with multiple criteria to meet, and at least two factors that influence achievement of those criteria. The user begins with a selected solution principle or system concept and a set of criteria that needs to be satisfied. The criteria may be expressed in terms of documented desirements or defined responses that the future system needs to achieve. Documented desirements can be imported into SynOptSys or created and documented directly within SynOptSys. Subsequent steps include identifying factors, specifying model order for each response, designing the experiment, running the experiment and gathering the data, analyzing the results, and determining the specifications for the optimized system. The user may also enter textual information as the project progresses. Data is easily edited within SynOptSys, and the software design enables full traceability within any step in the process, and facilitates reporting as needed. SynOptSys is unique in the way responses are defined and the nuances of the goodness associated with changes in response values for each of the responses of interest. The Desirability Optimization Methodology provides the basis of this novel feature. Moreover, this is a complete, guided design and optimization process tool with embedded math that can remain invisible to the user. It is not a standalone statistical program; it is a design and optimization system.

  15. Helminth parasites of the raccoon (Procyon lotor) from north-central Arkansas.

    PubMed

    Richardson, D J; Owen, W B; Snyder, D E

    1992-02-01

    Twenty-three species of helminths (4 trematodes, 2 cestodes, 14 nematodes, and 3 acanthocephalans) were found in the gastrointestinal tract, lungs, pancreas, tongue, urinary bladder, and subcutaneous tissues of 30 live-trapped or hunter-shot raccoons from north-central Arkansas between November 1989 and April 1990. Helminths were not detected in the brain, diaphragm, gallbladder, heart, liver, reproductive system, or trachea. Each raccoon examined was infected with 3 or more of the following helminths: Brachylaima virginiana, Eurytrema procyonis, Fibricola cratera, Pharyngostomoides procyonis, Atriotaenia procyonis, Mesocestoides spp., Arthrocephalus lotoris, Capillaria aerophila, Capillaria plica, Capillaria procyonis, Capillaria putorii, Crenosoma goblei, Cruzia americana, Dirofilaria tenuis, Dracunculus insignis, Enterobius sp., Gnathostoma procyonis, Molineus barbatus, Physaloptera rara, Trichinella spiralis, Centrorhynchus wardae, Macracanthorhynchus ingens, and Oligacanthorhynchus tortuosa. All helminths collected with the exception of D. insignis constitute new geographic distribution records. Occurrences of C. aerophila, C. wardae, and O. tortuosa are new host records. One nymphal pentastome, Porocephalus crotali, was found in the liver of 1 raccoon, constituting a new host record.

  16. Plica Polonica in a Patient on Chemotherapy: A Case Report with Review of Literature

    PubMed Central

    Gupta, Savera; Kumar, Ramesh; Vijay, Anita; Jain, Suresh Kumar

    2017-01-01

    Plica polonica (plica neuropathica) is an uncommon entity characterized by irreversible twisting and matting of hair resulting in a hard impermeable mass of keratin. Although the exact mechanism is not fully understood, it has been attribute to longitudinal splitting or weathering of hair shaft due to vigorous friction and frequent use of harsh shampoos and harsh cleansers and/or due to keeping long hair with poor hair care or neglect, parasitic infection. We describe an unusual case of plica polonica occurring in a patient of lung adenocarcinoma on chemotherapy and review the literature. Anagen effluvium due to chemotherapy (paclitaxel and carboplatin) and use of an uncustomary shampoo by the patient are the causative factors for matting of the hair. PMID:28932066

  17. Is posterior synovial plica excision necessary for refractory lateral epicondylitis of the elbow?

    PubMed

    Rhyou, In Hyeok; Kim, Kang Wook

    2013-01-01

    Arthroscopic treatments for lateral epicondylitis including débridement of the extensor carpi radialis brevis (ECRB) origin (Baker technique) or resection of the radiocapitellar synovial plica reportedly improve symptoms. However the etiology of the disease and the role of the plica remain unclear. We asked if posterior radiocapitellar synovial plica excision made any additional improvement in pain or function after arthroscopic ECRB release. We retrospectively reviewed 38 patients who had arthroscopic treatment for refractory lateral epicondylitis between November 2003 and October 2009. Twenty patients (Group A) underwent the Baker technique and 18 patients (Group B) underwent a combination of the Baker technique and posterior synovial plica excision. The minimum followup was 36 months (mean, 46 months; range, 36-72 months) for Group A and 25 months (mean, 30 months; range, 25-36 months) for Group B. Postoperatively we obtained VAS pain and DASH scores for each group. Two years postoperatively, we found no differences in the VAS pain score or DASH: the mean VAS pain scores were 0.3 points in Group A and 0.4 points in Group B, and the DASH scores were 5.1 points and 6.1 points respectively. The addition of débridement of the posterior synovial fold did not appear to enhance either pain relief or function compared with the classic Baker technique without decortication.

  18. Matrix Metalloproteases and Tissue Inhibitors of Metalloproteinases in Medial Plica and Pannus-like Tissue Contribute to Knee Osteoarthritis Progression

    PubMed Central

    Yang, Chih-Chang; Lin, Cheng-Yu; Wang, Hwai-Shi; Lyu, Shaw-Ruey

    2013-01-01

    Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologic changes in the joints. However, the pathogenic effects of synovial tissue inflammation on OA knees are not clear. To investigate whether the inflammation caused by the medial plica is involved in the pathogenesis of osteoarthritis, we examined the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the medial plica and pannus-like tissue in the knees of patients with medial compartment OA who underwent either arthroscopic medial release (stage II; 15 knee joints from 15 patients) or total knee replacement (stage IV; 18 knee joints from 18 patients). MMP-2, MMP-3, MMP-9, IL-1β, and TNF-α mRNA and protein levels measured, respectively, by quantitative real-time PCR and Quantibody human MMP arrays, were highly expressed in extracts of medial plica and pannus-like tissue from stage IV knee joints. Immunohistochemical staining also demonstrated high expression of MMP-2, MMP-3, and MMP-9 in plica and pannus-like tissue of stage IV OA knees and not in normal cartilage. Some TIMP/MMP ratios decreased significantly in both medial plica and pannus-like tissue as disease progressed from stage II to stage IV. Furthermore, the migration of cells from the pannus-like tissue was enhanced by IL-1β, while plica cell migration was enhanced by TNF-α. The results suggest that medial plica and pannus-like tissue may be involved in the process of cartilage degradation in medial compartment OA of the knee. PMID:24223987

  19. Matrix metalloproteases and tissue inhibitors of metalloproteinases in medial plica and pannus-like tissue contribute to knee osteoarthritis progression.

    PubMed

    Yang, Chih-Chang; Lin, Cheng-Yu; Wang, Hwai-Shi; Lyu, Shaw-Ruey

    2013-01-01

    Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologic changes in the joints. However, the pathogenic effects of synovial tissue inflammation on OA knees are not clear. To investigate whether the inflammation caused by the medial plica is involved in the pathogenesis of osteoarthritis, we examined the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the medial plica and pannus-like tissue in the knees of patients with medial compartment OA who underwent either arthroscopic medial release (stage II; 15 knee joints from 15 patients) or total knee replacement (stage IV; 18 knee joints from 18 patients). MMP-2, MMP-3, MMP-9, IL-1β, and TNF-α mRNA and protein levels measured, respectively, by quantitative real-time PCR and Quantibody human MMP arrays, were highly expressed in extracts of medial plica and pannus-like tissue from stage IV knee joints. Immunohistochemical staining also demonstrated high expression of MMP-2, MMP-3, and MMP-9 in plica and pannus-like tissue of stage IV OA knees and not in normal cartilage. Some TIMP/MMP ratios decreased significantly in both medial plica and pannus-like tissue as disease progressed from stage II to stage IV. Furthermore, the migration of cells from the pannus-like tissue was enhanced by IL-1β, while plica cell migration was enhanced by TNF-α. The results suggest that medial plica and pannus-like tissue may be involved in the process of cartilage degradation in medial compartment OA of the knee.

  20. [Plica polonica in the 21st century].

    PubMed

    Friedli, A; Pierriard-Wolfensberger, J; Harms, M

    2000-03-01

    We describe a young man presenting with dreadlocks. There are remarkable similarities with the so called plica polonica, that historically had been treated with long courses of mercury. Apparently very important in the 18th century, the interest for this hair-disorder appears to be lost in specialized medical literature. In contrast dreadlocks, a recent hairstyle are frequently encountered. Lack of other sources various websites provide dermatologists with answers to questions regarding complications. Fortunately a simply haircut is today treatment enough.

  1. Capillaria (Hepatocapillaria) cichlasomae (Nematoda: Capillariidae) from the liver of the cichlid fish Cichlasoma urophthalmus from Yucatan, Mexico.

    PubMed

    Moravec, F; Scholz, T; Mendoza Franco, E

    1995-01-01

    Capillaria (Hepatocapillaria) cichlasomae sp. n., parasitic in the liver of the cichlid Cichlasoma urophthalmus (Günther) from a small freshwater lake ("aguada") Xpoc in Yucatan, Mexico, is described. The parasite is characterized mainly by its small body size (male 1.8 mm, female 4.5 mm), the structure of the stichosome (markedly short stichocytes in one row) and the male (the presence of a pair of small subventral postanal papillae) and female (anus distinctly subterminal) caudal ends, and by the size and structure of the spicule (spicule 0.068-0.085 mm long, with marked transverse grooves on surface) and eggs (size 0.053-0.058 x 0.023 mm, with protruding polar plugs). This is the second known Capillaria species from the liver of fish and the first one from the liver of a freshwater fish.

  2. Intra-articular plica causing ankle impingement in a young handball player: a case report.

    PubMed

    Somorjai, Nicolaas; Jong, Bob; Draijer, W F

    2013-01-01

    Ankle sprains are common injuries that respond well to rehabilitation. In the case of persisting symptoms, the differential diagnosis should include osteochondral defects, tendon injury, mechanical instability, and ankle impingement. In the present case report, we describe a 16-year-old male handball player who presented with persisting pain and locking in the right ankle 3 years after having sustained multiple minor inversion trauma. The clinical examination and conventional radiography showed no abnormalities. On magnetic resonance imaging, a flake fracture at the anteromedial talar dome and/or loose body was assumed. Arthroscopic examination revealed an intra-articular plica originating from an osteochondral fossa at the anteromedial tibial plafond. The plica was debrided. Retrospectively, the arthroscopic findings matched the radiographs and magnetic resonance images. The postoperative protocol consisted of early mobilization. At 6 weeks of follow-up, the patient had no pain and had returned to his sports activities. The present case report illustrates, to the best of our knowledge, the first case of ankle impingement due to a, most likely congenital, intra-articular plica arising from an osteochondral fossa at the anteromedial tibial plafond. This rare clinical condition can be diagnosed with magnetic resonance imaging. Arthroscopic debridement will effectively relieve the symptoms. Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  3. CERES SYN1deg Ed4 Product Removal

    Atmospheric Science Data Center

    2016-04-18

    ... The CERES Synoptic One Degree Edition4A product family, SYN1deg-1Hour, SYN1deg-3Hour, SYN1deg-MHour, SYN1deg-Day, and SYN1deg-Month with Configuration Code 400404 was pulled from public view after two errors were identified.   The first issue ...

  4. Occurrence of Capillaria sp. in the liver of sheep (Ovis aries ) in a slaughterhouse in the state of Acre, Brazil.

    PubMed

    Teixeira, Paulo Eduardo Ferlini; Corrêa, Christiane Leal; Oliveira, Fernanda Bittencourt de; Alencar, Alba Cristina Miranda de Barros; Neves, Leandro Batista das; Garcia, Daniel Daipert; Almeida, Fernanda Barbosa de; Pereira, Luis Cláudio Muniz; Machado-Silva, José Roberto; Rodrigues-Silva, Rosângela

    2018-01-01

    Although sheep farming has grown in the state of Acre over the past four decades, little is known about occurrences of helminthiases in the herds of this region. The objective of the study was to assess the occurrences of non-intestinal helminthiasis among sheep slaughtered in Rio Branco. A total of 110 sheep livers were inspected from two slaughter batches (july 2014 and march 2015) in a slaughterhouse in Rio Branco. Livers with macroscopic lesions were photographed and were then subjected to histopathological analysis under an optical microscope. The macroscopic lesions showed small nodes with inflammatory characteristics and areas of fibrosis, which appeared to be calcified, thus suggesting a granulomatous reaction. Of the 110 evaluated livers, we noticed 110 nodules in total; these nodules have an average size of 0.5 cm. The histopathological analysis showed alterations to the architecture of the hepatic lobe, with multiple foci of necrosis and polymorphonuclear cells. Two samples revealed the presence of helminths from Nematode class and Capillaria sp. eggs identified by the typical morphology and morphometry. This seems to be the first report of Capillaria sp. in sheep livers in Brazil, and it serves as an important alert regarding animal health surveillance and control and regarding the Capillaria sp. zoonotic role in humans.

  5. Helminths of the raccoon (Procyon lotor) in western Kentucky.

    PubMed

    Cole, R A; Shoop, W L

    1987-08-01

    Seventy raccoons (Procyon lotor) from western Kentucky were examined for helminths from December 1985 through May 1986. Twenty-three species of helminths were collected including 10 species of Trematoda (Brachylaima virginiana, Euryhelmis squamula, Eurytrema procyonis, Fibricola cratera, Gyrosoma singulare, Maritreminoides nettae, Mesostephanus appendiculatoides, Metagonimoides oregonensis, Paragonimus kellicotti, Pharyngostomoides procyonis), 2 species of Cestoda (Atriotaenia procyonis, Mesocestoides variabilis), 10 species of Nematoda (Arthrocephalus lotoris, Baylisascaris procyonis, Capillaria putorii, C. plica, Crenosoma goblei, Dracunculus insignis, Gnathostoma procyonis, Molineus barbatus, Physaloptera rara, Trichinella spiralis), and 1 species of Acanthocephala (Macracanthorhynchus ingens). A mean of 6.4 (3-11) helminth species per host was recorded. Fibricola cratera, Atriotaenia procyonis, Mesocestoides variabilis, Arthrocephalus lotoris, Capillaria plica, Dracunculus insignis, Molineus barbatus, and Physaloptera rara were ubiquitous parasites of the raccoon, whereas specific nidi were observed for Eurytrema procyonis, Gyrosoma singulare, Paragonimus kellicotti, Baylisascaris procyonis, Trichinella spiralis, and Macracanthorhyncus ingens. With an overall prevalence of 10% or higher, 15 of the 23 helminth species were considered common parasites of the raccoon in western Kentucky. When the 10% prevalence rate was applied within geographical quadrants to correct for the presence of nidi it was found that 18 of the 23 helminth species were common and 5 were regarded as rare parasites of the raccoon. Two species of nematodes, T. spiralis and B. procyonis, displayed a markedly higher prevalence in male raccoons.

  6. Stereospecific synthesis of syn-α-oximinoamides by a three-component reaction of isocyanides, syn-chlorooximes, and carboxylic acids.

    PubMed

    Pirali, Tracey; Mossetti, Riccardo; Galli, Simona; Tron, Gian Cesare

    2011-07-15

    A stereospecific multicomponent reaction among isocyanides, syn-chlorooximes, and carboxylic acids provides an efficient synthesis of biologically relevant syn-α-oximinoamides. © 2011 American Chemical Society

  7. Rosebud SynCoal Partnership, SynCoal{reg_sign} demonstration technology update

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sheldon, R.W.

    1997-12-31

    An Advanced Coal Conversion Process (ACCP) technology being demonstrated in eastern Montana (USA) at the heart of one of the world`s largest coal deposits is providing evidence that the molecular structure of low-rank coals can be altered successfully to produce a unique product for a variety of utility and industrial applications. The product is called SynCoal{reg_sign} and the process has been developed by the Rosebud SynCoal Partnership (RSCP) through the US Department of Energy`s multi-million dollar Clean Coal Technology Program. The ACCP demonstration process uses low-pressure, superheated gases to process coal in vibrating fluidized beds. Two vibratory fluidized processing stagesmore » are used to heat and convert the coal. This is followed by a water spray quench and a vibratory fluidized stage to cool the coal. Pneumatic separators remove the solid impurities from the dried coal. There are three major steps to the SynCoal{reg_sign} process: (1) thermal treatment of the coal in an inert atmosphere, (2) inert gas cooling of the hot coal, and (3) removal of ash minerals. When operated continuously, the demonstration plant produces over 1,000 tons per day (up to 300,000 tons per year) of SynCoal{reg_sign} with a 2% moisture content, approximately 11,800b Btu/lb and less than 1.0 pound of SO{sub 2} per million Btu. This product is obtained from Rosebud Mine sub-bituminous coal which starts with 25% moisture, 8,600 Btu/lb and approximately 1.6 pounds of SO{sub 2} per million Btu.« less

  8. Running Injuries: The Infrapatellar Fat Pad and Plica Injuries.

    PubMed

    McConnell, Jenny

    2016-02-01

    When considering knee pain in runners, clinicians differentiate sources of symptoms and determine their cause. Knee problems arise when a runner increases the amount/frequency of the loading through the lower limb. The way the loading is distributed through the knee determines which tissues are abnormally loaded. Knee problems cannot be considered in isolation, requiring a thorough investigation of static and dynamic lower limb mechanics, and footwear and surfaces. This article examines potential sources of knee pain and explores the role of the infrapatellar fat pad and synovial plica in the mechanics of the knee and its involvement in knee symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. STUDY OF THE PREVALENCE OF Capillaria hepatica IN HUMANS AND RODENTS IN AN URBAN AREA OF THE CITY OF PORTO VELHO, RONDÔNIA, BRAZIL

    PubMed Central

    da Rocha, Elierson José Gomes; Basano, Sérgio de Almeida; de Souza, Márcia Maria; Honda, Eduardo Resende; de Castro, Márcio Botelho; Colodel, Edson Moleta; Silva, Jéssica Carolinne Damasceno e; Barros, Lauro Prado; Rodrigues, Elisa Sousa; Camargo, Luís Marcelo Aranha

    2015-01-01

    Introduction: Hepatic capillariosis, caused by Capillaria hepatica (Calodium hepaticum) (Bancroft, 1893), Travassos, 1915 (Nematoda, Trichinelloidea, Capillariidae), is a common zoonosis in rodents but is rare in humans. Seventy-two cases in humans have been reported worldwide since the first case was described by MACARTHUR in 192417,27. This study aimed to determine the prevalence of Capillaria hepatica in humans and rodents in an urban area of Porto Velho, the capital of Rondônia, in Brazil. Methods: After conducting a census of the area, 490 residents were randomly selected, and, after signing a term of consent, provided blood samples that were screened for anti-Capillaria hepatica antibodies. Simultaneously, rats were captured to assess the prevalence of this parasite in rodents by histopathological examination in liver sections. Results: A prevalence of 1.8% was found among residents who had specific antibodies at a dilution of 1:150, indicating exposure to parasite eggs; 0.8% of the subjects also had positive titers at a dilution of 1:400, indicating true infection. The prevalence in rats was 2%. Conclusions: The prevalence of infection with this parasite among humans and rats was low. While the prevalence encountered among humans was within the limits reported in the literature, the prevalence among rodents was much lower. PMID:25651325

  10. Registration and Release of Syn1RR tall fescue

    USDA-ARS?s Scientific Manuscript database

    The Agricultural Research Service of the United States DepaRRment of Agriculture announces the release of the new tall fescue [Festuca arundinacea (syn., Lolium arundinaceum Darbyshire; Schedonorus phoenix (Scop.) Holub)] cultivar Syn1RR. Syn1RR is a rust tolerant tall fescue cultivar that exhibits...

  11. Capillaria plectropomi n. sp. (Nematoda: Capillariidae), a new intestinal parasite of the leopard coral grouper Plectropomus leopardus (Serranidae) off New Caledonia

    PubMed Central

    Moravec, František; Justine, Jean-Lou

    2014-01-01

    A new nematode species, Capillaria plectropomi n. sp. (Capillariidae), is described from the intestine of the leopard coral grouper Plectropomus leopardus (Lacepède) from coral reefs off New Caledonia. The new species, belonging to the subgenus Neocapillaria Moravec, 1987, differs from other congeneric species of this subgenus from marine fishes mainly in the length (168–186 μm), shape and structure of the spicule. It is characterized, in the male, by the presence of two well-developed dorsolateral caudal lobes, a pair of lateral papillae, a heavily sclerotized spicule with many rough transverse grooves in the middle part, a spinose spicular sheath, and in the female, by eggs measuring 60–66 × 27 μm without protruding polar plugs. The buccal cavity contains a small finger-shaped stylet. Capillaria plectropomi n. sp. is the first known species of this genus parasitizing fishes of the perciform family Serranidae. PMID:25531932

  12. Molecular detection of Capillaria philippinensis: An emerging zoonosis in Egypt.

    PubMed

    El-Dib, Nadia A; El-Badry, Ayman A; Ta-Tang, Thuy-Huong; Rubio, Jose M

    2015-07-01

    Human infection with Capillaria philippinensis is accidental; however, it may end fatally if not diagnosed and treated in the proper time. The first case was detected in the Philippines in 1963, but later reported in other countries around the world, including Egypt. In this report, molecular diagnosis using a specific nested PCR for detection of C. philippinensis in faeces is described based on the amplification of small ribosomal subunit. The test showed sensitivity and specificity, as it detected all the positive cases and gave no cross-reaction with human DNA and DNA of other tested parasites. This method can be very useful not only for improvement of diagnosis, but also to understand the different environmental routes of transmission by detection of C. philippinensis DNA-stages in the possible fish intermediate hosts and reservoir animal host, helping to improve strategies for surveillance and prevention of human disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Py4Syn: Python for synchrotrons.

    PubMed

    Slepicka, H H; Canova, H F; Beniz, D B; Piton, J R

    2015-09-01

    In this report, Py4Syn, an open-source Python-based library for data acquisition, device manipulation, scan routines and other helper functions, is presented. Driven by easy-to-use and scalability ideals, Py4Syn offers control system agnostic solution and high customization level for scans and data output, covering distinct techniques and facilities. Here, most of the library functionalities are described, examples of use are shown and ideas for future implementations are presented.

  14. One-Pot Catalytic Enantio- and Diastereoselective Syntheses of anti-, syn-cis-Disubstituted, and syn-Vinyl Cyclopropyl Alcohols

    PubMed Central

    Kim, Hun Young; Salvi, Luca; Carroll, Patrick J.; Walsh, Patrick J.

    2009-01-01

    Highly enantio- and diastereoselective methods for the synthesis of a variety of cyclopropyl alcohols are reported. These methods represent the first one-pot approaches to syn-vinyl cyclopropyl alcohols, syn-cis-disubstituted cyclopropyl alcohols, and anti-cyclopropyl alcohols from achiral precursors. The methods begin with enantioselective C–C bond formations promoted by a MIB-based zinc catalyst to generate allylic alkoxide intermediates. The intermediates are then subjected to in situ alkoxide-directed cyclopropanation to provide cyclopropyl alcohols. In the synthesis of vinyl cyclopropyl alcohols, hydroboration of enynes is followed by transmetalation of the resulting dienylborane to zinc to provide dienylzinc reagents. Enantioselective addition to aldehydes generates the requisite dienyl zinc alkoxides, which are then subjected to in situ cyclopropanation to furnish vinyl cyclopropyl alcohols. Cyclopropanation occurs at the double bond allylic to the alkoxide. Using this method, syn-vinylcyclopropyl alcohols are obtained in 65–85% yield, 76–93% ee, and >19:1 dr. To prepare anti-cyclopropanols, enantioselective addition of alkylzinc reagents to conjugated enals provides allylic zinc alkoxides. Because direct cyclopropanation provides syn-cyclopropyl alcohols, the intermediate allylic alkoxides were treated with TMSCl/Et3N to generate intermediate silyl ethers. In situ cyclopropanation of the allylic silyl ether resulted in cyclopropanation to form the anti-cyclopropyl silyl ether. Workup with TBAF affords the anti-cyclopropyl alcohols in one-pot in 60–82% yield, 89–99% ee, and ≥10:1 dr. For the synthesis of cis-disubstituted cyclopropyl alcohols, in situ generated (Z)-vinyl zinc reagents were employed in asymmetric addition to aldehydes to generate (Z)-allylic zinc alkoxides. In situ cyclopropanation provides syn-cis-disubstituted cyclopropyl alcohols in 42–70% yield, 88–97% ee, and >19:1 dr. These one-pot procedures enable the synthesis of a

  15. Notice of release of Syn1 Tall Fescue

    USDA-ARS?s Scientific Manuscript database

    The Agricultural Research Service, U.S. Department of Agriculture announces the release of Syn1 tall fescue [Festuca arundinacea (syn., Lolium arundinaceum Darbyshire; Schedonorus phoenix (Scop.) Holub)] (PI xxxx, PI xxxx) germplasm developed by Dr. Bryan K. Kindiger at the USDA-ARS Grazinglands Res...

  16. The Existence of a Natural Plica at the Anatomical Base of the Antihelix and its Surgical Importance to Address Protruding Ears: An Anatomicosurgical Study.

    PubMed

    Oliveira, Miguel Marques; Oliveira, Daniel Sousa Marques; Oliveira, Gustavo Sousa Marques

    2017-04-01

    Protruding ears represent the main abnormality of the external ear, which has required numerous anatomic and surgical studies. Most studies give attention to the absence of the antihelix as the anatomic defect responsible for the clinical deformity of the lateral aspect of the ear that leads to its anteversion. The reason for this study is the controversial origin of the fold of the antihelix within the auricle framework, a field of interest for aesthetic otoplasty. The current study examined the medial surface of the cartilaginous ear frame from cadaver specimens with right morphology to investigate the starting point of the fold of the antihelix. This allowed for verification of a natural plica at the anatomic base of this antihelical fold, which to date has not had its topography described morphologically. It is acknowledged that relevant literature makes no reference to this innominate natural plica at the origin of the antihelix, whose anatomic and surgical importance is related in this report. This study aimed to show that the existence of a natural plica at the base of the antihelix in ear framing represents a landmark between normal and protruding ear morphology. For 8 years, 118 ears were carefully investigated within rigid ethical principles based on a thorough review of the pertinent literature. The study investigated 16 selected cadaver specimens and 102 protruding ears dissected by the senior author including 49 bilateral cases (26 males and 23 females) and 4 unilateral cases (2 males and 2 females). Bifacial anthropometric measurements by calipers were used for documentation. A natural plica at the base of the antihelix was found in all cadaver ears selected with right morphology, whereas it was totally absent in every surgically treated protruding ear irrespective of color, gender, age, or ethnic origin. Ambilateral measures of the antihelix eminence certify the study object in normal specimens as well as its lack in abnormal ones. Technical and

  17. Ankle Impingement Caused by an Intra-articular Plica: A Report of 2 Cases.

    PubMed

    Rosenbaum, Andrew J; Positano, Rock G; Positano, Rock C J; Dines, Joshua S

    2016-02-01

    Entrapment of soft tissues in the anterolateral gutter of the ankle can cause impingement. When symptomatic, patients complain of chronic ankle pain exacerbated with dorsiflexion. Symptoms of instability and a history of recurring ankle sprains are common findings. Plain radiographs and magnetic resonance imaging may assist clinicians in identifying associated pathology. We present 2 cases of ankle impingement occurring in the setting of equivocal examination and imaging findings. In both cases, arthroscopy revealed a likely congenital, intra-articular plica. Therapeutic, Level IV: Case Study. © 2015 The Author(s).

  18. SynBioSS-aided design of synthetic biological constructs.

    PubMed

    Kaznessis, Yiannis N

    2011-01-01

    We present walkthrough examples of using SynBioSS to design, model, and simulate synthetic gene regulatory networks. SynBioSS stands for Synthetic Biology Software Suite, a platform that is publicly available with Open Licenses at www.synbioss.org. An important aim of computational synthetic biology is the development of a mathematical modeling formalism that is applicable to a wide variety of simple synthetic biological constructs. SynBioSS-based modeling of biomolecular ensembles that interact away from the thermodynamic limit and not necessarily at steady state affords for a theoretical framework that is generally applicable to known synthetic biological systems, such as bistable switches, AND gates, and oscillators. Here, we discuss how SynBioSS creates links between DNA sequences and targeted dynamic phenotypes of these simple systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. [Helminth findings in indigenous raccoon dogs Nyctereutes procyonoides (Gray, 1843)].

    PubMed

    Thiess, A; Schuster, R; Nöckler, K; Mix, H

    2001-01-01

    Internal organs of 74 racoon dogs originating from the eastern districts of the Federal Land Brandenburg were subjected to a complete helminthological dissection. In addition, samples of diaphragma muscles from 46 further animals were examined for Trichinella larvae. Altogether 3 trematode- (Alaria alata, Isthmiophora melis, Metorchis bilis), 3 cestode- (Mesocestoides sp., Echinococcus multilocularis, Taenia polyacantha) and 7 nematode species (Capillaria aerophila, C. plica, Trichinella spiralis, Uncinaria stenocephala, Molineus patens, Crenosoma vulpis, Toxocara canis) could be identified. Thereby, the racoon dog has a comparable helminth spectrum as well known in red foxes. Differences in the frequency of the occurrence of helminths in both hosts can be explained by different food preferences.

  20. MaxSynBio - Avenues towards creating cells from the bottom up.

    PubMed

    Schwille, Petra; Spatz, Joachim; Landfester, Katharina; Bodenschatz, Eberhard; Herminghaus, Stephan; Sourjik, Victor; Erb, Tobias; Bastiaens, Philippe; Lipowsky, Reinhard; Hyman, Anthony; Dabrock, Peter; Baret, Jean-Christophe; Vidakovic-Koch, Tanja; Bieling, Peter; Dimova, Rumiana; Mutschler, Hannes; Robinson, Tom; Tang, Dora; Wegner, Seraphine; Sundmacher, Kai

    2018-05-11

    A large Max Planck-based German research consortium ('MaxSynBio') was formed to investigate living systems from a fundamental perspective. The research program of MaxSynBio relies solely on the bottom-up approach to Synthetic Biology. MaxSynBio focuses on the detailed analysis and understanding of essential processes of life, via their modular reconstitution in minimal synthetic systems. The ultimate goal is to construct a basic living unit entirely from non-living components. The fundamental insights gained from the activities in MaxSynBio can eventually be utilized for establishing a new generation of biotechnological processes, which would be based on synthetic cell constructs that replace natural cells currently used in conventional biotechnology. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. SynFind: Compiling Syntenic Regions across Any Set of Genomes on Demand.

    PubMed

    Tang, Haibao; Bomhoff, Matthew D; Briones, Evan; Zhang, Liangsheng; Schnable, James C; Lyons, Eric

    2015-11-11

    The identification of conserved syntenic regions enables discovery of predicted locations for orthologous and homeologous genes, even when no such gene is present. This capability means that synteny-based methods are far more effective than sequence similarity-based methods in identifying true-negatives, a necessity for studying gene loss and gene transposition. However, the identification of syntenic regions requires complex analyses which must be repeated for pairwise comparisons between any two species. Therefore, as the number of published genomes increases, there is a growing demand for scalable, simple-to-use applications to perform comparative genomic analyses that cater to both gene family studies and genome-scale studies. We implemented SynFind, a web-based tool that addresses this need. Given one query genome, SynFind is capable of identifying conserved syntenic regions in any set of target genomes. SynFind is capable of reporting per-gene information, useful for researchers studying specific gene families, as well as genome-wide data sets of syntenic gene and predicted gene locations, critical for researchers focused on large-scale genomic analyses. Inference of syntenic homologs provides the basis for correlation of functional changes around genes of interests between related organisms. Deployed on the CoGe online platform, SynFind is connected to the genomic data from over 15,000 organisms from all domains of life as well as supporting multiple releases of the same organism. SynFind makes use of a powerful job execution framework that promises scalability and reproducibility. SynFind can be accessed at http://genomevolution.org/CoGe/SynFind.pl. A video tutorial of SynFind using Phytophthrora as an example is available at http://www.youtube.com/watch?v=2Agczny9Nyc. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. N-glycosylation at the SynCAM (synaptic cell adhesion molecule) immunoglobulin interface modulates synaptic adhesion.

    PubMed

    Fogel, Adam I; Li, Yue; Giza, Joanna; Wang, Qing; Lam, Tukiet T; Modis, Yorgo; Biederer, Thomas

    2010-11-05

    Select adhesion molecules connect pre- and postsynaptic membranes and organize developing synapses. The regulation of these trans-synaptic interactions is an important neurobiological question. We have previously shown that the synaptic cell adhesion molecules (SynCAMs) 1 and 2 engage in homo- and heterophilic interactions and bridge the synaptic cleft to induce presynaptic terminals. Here, we demonstrate that site-specific N-glycosylation impacts the structure and function of adhesive SynCAM interactions. Through crystallographic analysis of SynCAM 2, we identified within the adhesive interface of its Ig1 domain an N-glycan on residue Asn(60). Structural modeling of the corresponding SynCAM 1 Ig1 domain indicates that its glycosylation sites Asn(70)/Asn(104) flank the binding interface of this domain. Mass spectrometric and mutational studies confirm and characterize the modification of these three sites. These site-specific N-glycans affect SynCAM adhesion yet act in a differential manner. Although glycosylation of SynCAM 2 at Asn(60) reduces adhesion, N-glycans at Asn(70)/Asn(104) of SynCAM 1 increase its interactions. The modification of SynCAM 1 with sialic acids contributes to the glycan-dependent strengthening of its binding. Functionally, N-glycosylation promotes the trans-synaptic interactions of SynCAM 1 and is required for synapse induction. These results demonstrate that N-glycosylation of SynCAM proteins differentially affects their binding interface and implicate post-translational modification as a mechanism to regulate trans-synaptic adhesion.

  3. N-Glycosylation at the SynCAM (Synaptic Cell Adhesion Molecule) Immunoglobulin Interface Modulates Synaptic Adhesion*

    PubMed Central

    Fogel, Adam I.; Li, Yue; Giza, Joanna; Wang, Qing; Lam, TuKiet T.; Modis, Yorgo; Biederer, Thomas

    2010-01-01

    Select adhesion molecules connect pre- and postsynaptic membranes and organize developing synapses. The regulation of these trans-synaptic interactions is an important neurobiological question. We have previously shown that the synaptic cell adhesion molecules (SynCAMs) 1 and 2 engage in homo- and heterophilic interactions and bridge the synaptic cleft to induce presynaptic terminals. Here, we demonstrate that site-specific N-glycosylation impacts the structure and function of adhesive SynCAM interactions. Through crystallographic analysis of SynCAM 2, we identified within the adhesive interface of its Ig1 domain an N-glycan on residue Asn60. Structural modeling of the corresponding SynCAM 1 Ig1 domain indicates that its glycosylation sites Asn70/Asn104 flank the binding interface of this domain. Mass spectrometric and mutational studies confirm and characterize the modification of these three sites. These site-specific N-glycans affect SynCAM adhesion yet act in a differential manner. Although glycosylation of SynCAM 2 at Asn60 reduces adhesion, N-glycans at Asn70/Asn104 of SynCAM 1 increase its interactions. The modification of SynCAM 1 with sialic acids contributes to the glycan-dependent strengthening of its binding. Functionally, N-glycosylation promotes the trans-synaptic interactions of SynCAM 1 and is required for synapse induction. These results demonstrate that N-glycosylation of SynCAM proteins differentially affects their binding interface and implicate post-translational modification as a mechanism to regulate trans-synaptic adhesion. PMID:20739279

  4. SYN-PEDS: SYNtactical Pediatric Evaluation and Diagnostic System

    PubMed Central

    Witten, Matthew; Maloney, David

    1980-01-01

    SYN-PEDS is a multimodular system which is designed to be an inhome interactive access to a neonatal and pediatric diagnostic information database. This system is designed to assist a parent in assessing his child's condition, as well as in determining whether or not the child needs immediate medical attention. This system is not designed to replace the pediatrician but rather, it is designed as a preventative and health maintenance information system which has the unusually nice side benefit if helping to reduce medical system costs by cutting down on the number of unnecessary visits to private and local clinics as well as private physicians. The current version of SYN-PEDS is composed of of four operative modules: CRITICAL, TREAT, CLINFO, and DIAGNOSE/SYMPTM. These four modules allow the parent/user to interact with the SYN-PEDS system in various modes. As an example, CLINFO is the module which provides clinical information on a variety of subjects. This module is for a parent who wishes information on a particular subject of interest.

  5. Capillaria hepatica in wild Norway rats (Rattus norvegicus) from Vancouver, Canada.

    PubMed

    Rothenburger, Jamie L; Himsworth, Chelsea G; Chang, Victoria; LeJeune, Manigandan; Leighton, Frederick A

    2014-07-01

    Capillaria hepatica is a parasitic nematode that infects the liver of rats (Rattus spp.), and occasionally other mammalian species, including humans. Despite its broad geographic distribution and host range, the ecology of this parasite remains poorly understood. We characterized the ecology of C. hepatica in urban Norway rats (Rattus norvegicus) in Vancouver, Canada. The overall prevalence of C. hepatica among Norway rats was 36% (241/671); however, there was significant variation in prevalence among city blocks. Using a generalized linear mixed model to control for clustering by block (where OR is odds ratio and CI is confidence interval), we found C. hepatica infection was negatively associated with season (spring [OR=0.14, 95% CI=0.05-0.39]; summer [OR=0.14, 95% CI=0.03-0.61]; winter [OR=0.34, 95% CI=0.13-0.84], compared to fall) and positively associated with sexual maturity (OR: 7.29, 95% CI=3.98-13.36) and presence of cutaneous bite wounds (OR=1.87, 95% CI=1.11-3.16). Our understanding of the ecology of C. hepatica in rats is hindered by a paucity of data regarding the main mechanisms of transmission (e.g., environmental exposure vs. active cannibalism). However, associations among infection, season, maturity, and bite wounds could suggest that social interactions, possibly including cannibalism, may be important in transmission.

  6. SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic vesicle cycling and axon outgrowth

    PubMed Central

    Corradi, Anna; Fadda, Manuela; Piton, Amélie; Patry, Lysanne; Marte, Antonella; Rossi, Pia; Cadieux-Dion, Maxime; Gauthier, Julie; Lapointe, Line; Mottron, Laurent; Valtorta, Flavia; Rouleau, Guy A.; Fassio, Anna; Benfenati, Fabio; Cossette, Patrick

    2014-01-01

    An increasing number of genes predisposing to autism spectrum disorders (ASDs) has been identified, many of which are implicated in synaptic function. This ‘synaptic autism pathway’ notably includes disruption of SYN1 that is associated with epilepsy, autism and abnormal behavior in both human and mice models. Synapsins constitute a multigene family of neuron-specific phosphoproteins (SYN1-3) present in the majority of synapses where they are implicated in the regulation of neurotransmitter release and synaptogenesis. Synapsins I and II, the major Syn isoforms in the adult brain, display partially overlapping functions and defects in both isoforms are associated with epilepsy and autistic-like behavior in mice. In this study, we show that nonsense (A94fs199X) and missense (Y236S and G464R) mutations in SYN2 are associated with ASD in humans. The phenotype is apparent in males. Female carriers of SYN2 mutations are unaffected, suggesting that SYN2 is another example of autosomal sex-limited expression in ASD. When expressed in SYN2  knockout neurons, wild-type human Syn II fully rescues the SYN2 knockout phenotype, whereas the nonsense mutant is not expressed and the missense mutants are virtually unable to modify the SYN2 knockout phenotype. These results identify for the first time SYN2  as a novel predisposing gene for ASD and strengthen the hypothesis that a disturbance of synaptic homeostasis underlies ASD. PMID:23956174

  7. Novel syn intramolecular pathway in base-catalyzed 1,2-elimination reactions of beta-acetoxy esters.

    PubMed

    Mohrig, Jerry R; Carlson, Hans K; Coughlin, Jane M; Hofmeister, Gretchen E; McMartin, Lea A; Rowley, Elizabeth G; Trimmer, Elizabeth E; Wild, Andrew J; Schultz, Steve C

    2007-02-02

    As part of a comprehensive investigation of electronic effects on the stereochemistry of base-catalyzed 1,2-elimination reactions, we observed a new syn intramolecular pathway in the elimination of acetic acid from beta-acetoxy esters and thioesters. 1H and 2H NMR investigation of reactions using stereospecifically labeled tert-butyl (2R*,3R*)-3-acetoxy-2,3-2H2-butanoate (1) and its (2R*,3S*) diastereomer (2) shows that 23 +/- 2% syn elimination occurs. The elimination reactions were catalyzed with KOH or (CH3)4NOH in ethanol/water under rigorously non-ion-pairing conditions. By contrast, the more sterically hindered beta-trimethylacetoxy ester produces only 6 +/- 1% syn elimination. These data strongly support an intramolecular (Ei) syn path for elimination of acetic acid, most likely through the oxyanion produced by nucleophilic attack at the carbonyl carbon of the beta-acetoxy group. The analogous thioesters, S-tert-butyl (2R*,3R*)-3-acetoxy-2,3-2H2-butanethioate (3) and its (2R*,3S*) diastereomer (4), showed 18 +/- 2% syn elimination, whereas the beta-trimethylacetoxy substrate gave 5 +/- 1% syn elimination. The more acidic thioester substrates do not produce an increased amount of syn stereoselectivity even though their elimination reactions are at the E1cb interface.

  8. Stereodivergent Synthesis of 1,3-Syn-Polyol Natural Product for Stereochemical-Based Structure Activity Relationship Studies

    NASA Astrophysics Data System (ADS)

    Zheng, Jiamin

    The 1,3-syn-diol functionality is very common in many natural products. An important class containing this moiety are the 1,3-syn-polyol/pyranone natural products, which have been isolated from a variety of plant sources, and possess biological activities like plant growth inhibition as well as antifeedant, antifungal, antibacterial, and antitumor properties. The feature of this class is a 6-membered lactone where the lactoe oxygen is part of a 1,3-syn-diol motif. To pursue the 1,3-syn-polyol/pyranone natural products, an iterative hydration of polyene strategy was utilized to provide the 1,3- syn-diol functionality, and asymmetric synthetic strategies were explored to form the requisite stereochemistry. The versatility of the asymmetric approach was demonstrated in the synthesis of eupatorium pyranone and also in an ongoing project aimed at the synthesis of SIA7248. As an outgrowth of our work on the total syntheses of 1,3-syn -polyol natural products inspired a stereo-divergent synthesis of 1,3-syn-polyol natural products and their analogs for stereochemical-based structure-activity relationship (SSAR) studies. To identify the key structural factors important for the anticancer activity of the 1,3-syn-polyol/pyranones, a stereo-divergent 16-member library of pyranone/polyol congeners was designed, synthesized and tested with variations in both stereochemistry and numbers of polyol repeat units. Having access to stereochemical isomers of the biologically active natural products allowed us to design experiments that help illustrate their mechanisms of action.

  9. ImSyn: photonic image synthesis applied to synthetic aperture radar, microscopy, and ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Turpin, Terry M.; Lafuse, James L.

    1993-02-01

    ImSynTM is an image synthesis technology, developed and patented by Essex Corporation. ImSynTM can provide compact, low cost, and low power solutions to some of the most difficult image synthesis problems existing today. The inherent simplicity of ImSynTM enables the manufacture of low cost and reliable photonic systems for imaging applications ranging from airborne reconnaissance to doctor's office ultrasound. The initial application of ImSynTM technology has been to SAR processing; however, it has a wide range of applications such as: image correlation, image compression, acoustic imaging, x-ray tomographic (CAT, PET, SPECT), magnetic resonance imaging (MRI), microscopy, range- doppler mapping (extended TDOA/FDOA). This paper describes ImSynTM in terms of synthetic aperture microscopy and then shows how the technology can be extended to ultrasound and synthetic aperture radar. The synthetic aperture microscope (SAM) enables high resolution three dimensional microscopy with greater dynamic range than real aperture microscopes. SAM produces complex image data, enabling the use of coherent image processing techniques. Most importantly SAM produces the image data in a form that is easily manipulated by a digital image processing workstation.

  10. Molecular and Behavioral Changes Associated with Adult Hippocampus-Specific SynGAP1 Knockout

    ERIC Educational Resources Information Center

    Muhia, Mary; Willadt, Silvia; Yee, Benjamin K.; Feldon, Joram; Paterna, Jean-Charles; Schwendener, Severin; Vogt, Kaspar; Kennedy, Mary B.; Knuesel, Irene

    2012-01-01

    The synaptic Ras/Rap-GTPase-activating protein (SynGAP1) plays a unique role in regulating specific downstream intracellular events in response to N-methyl-D-aspartate receptor (NMDAR) activation. Constitutive heterozygous loss of SynGAP1 disrupts NMDAR-mediated physiological and behavioral processes, but the disruptions might be of developmental…

  11. Deep functional analysis of synII, a 770 kb synthetic yeast chromosome

    PubMed Central

    Gao, Feng; Gong, Jianhui; Abramczyk, Dariusz; Walker, Roy; Zhao, Hongcui; Chen, Shihong; Liu, Wei; Luo, Yisha; Müller, Carolin A.; Paul-Dubois-Taine, Adrien; Alver, Bonnie; Stracquadanio, Giovanni; Mitchell, Leslie A.; Luo, Zhouqing; Fan, Yanqun; Zhou, Baojin; Wen, Bo; Tan, Fengji; Wang, Yujia; Zi, Jin; Xie, Zexiong; Li, Bingzhi; Yang, Kun; Richardson, Sarah M.; Jiang, Hui; French, Christopher E.; Nieduszynski, Conrad A.; Koszul, Romain; Marston, Adele L.; Yuan, Yingjin; Wang, Jian; Bader, Joel S.; Dai, Junbiao; Boeke, Jef D.; Xu, Xun; Cai, Yizhi; Yang, Huanming

    2017-01-01

    Herein we report the successful design, construction and characterization of a 770 kb synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels, including phenomics, transcriptomics, proteomics, chromosome segregation and replication analysis to provide a thorough and comprehensive analysis of a synthetic chromosome. Our “Trans-Omics” analyses reveal a modest but potentially significant pervasive up-regulation of translational machinery observed in synII is mainly caused by the deletion of 13 tRNAs. By both complementation assays and SCRaMbLE, we targeted and debuged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the HOG response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain. PMID:28280153

  12. Wnt-related SynGAP1 is a neuroprotective factor of glutamatergic synapses against Aβ oligomers

    PubMed Central

    Codocedo, Juan F.; Montecinos-Oliva, Carla; Inestrosa, Nibaldo C.

    2015-01-01

    Wnt-5a is a synaptogenic factor that modulates glutamatergic synapses and generates neuroprotection against Aβ oligomers. It is known that Wnt-5a plays a key role in the adult nervous system and synaptic plasticity. Emerging evidence indicates that miRNAs are actively involved in the regulation of synaptic plasticity. Recently, we showed that Wnt-5a is able to control the expression of several miRNAs including miR-101b, which has been extensively studied in carcinogenesis. However, its role in brain is just beginning to be explored. That is why we aim to study the relationship between Wnt-5a and miRNAs in glutamatergic synapses. We performed in silico analysis which predicted that miR-101b may inhibit the expression of synaptic GTPase-Activating Protein (SynGAP1), a Ras GTPase-activating protein critical for the development of cognition and proper synaptic function. Through overexpression of miR-101b, we showed that miR-101b is able to regulate the expression of SynGAP1 in an hippocampal cell line. Moreover and consistent with a decrease of miR-101b, Wnt-5a enhances SynGAP expression in cultured hippocampal neurons. Additionally, Wnt-5a increases the activity of SynGAP in a time-dependent manner, with a similar kinetic to CaMKII phosphorylation. This also, correlates with a modulation in the SynGAP clusters density. On the other hand, Aβ oligomers permanently decrease the number of SynGAP clusters. Interestingly, when neurons are co-incubated with Wnt-5a and Aβ oligomers, we do not observe the detrimental effect of Aβ oligomers, indicating that, Wnt-5a protects neurons from the synaptic failure triggered by Aβ oligomers. Overall, our findings suggest that SynGAP1 is part of the signaling pathways induced by Wnt-5a. Therefore, possibility exists that SynGAP is involved in the synaptic protection against Aβ oligomers. PMID:26124704

  13. Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1.

    PubMed

    Park, Kellie A; Ribic, Adema; Laage Gaupp, Fabian M; Coman, Daniel; Huang, Yuegao; Dulla, Chris G; Hyder, Fahmeed; Biederer, Thomas

    2016-07-13

    Select adhesion proteins control the development of synapses and modulate their structural and functional properties. Despite these important roles, the extent to which different synapse-organizing mechanisms act across brain regions to establish connectivity and regulate network properties is incompletely understood. Further, their functional roles in different neuronal populations remain to be defined. Here, we applied diffusion tensor imaging (DTI), a modality of magnetic resonance imaging (MRI), to map connectivity changes in knock-out (KO) mice lacking the synaptogenic cell adhesion protein SynCAM 1. This identified reduced fractional anisotropy in the hippocampal CA3 area in absence of SynCAM 1. In agreement, mossy fiber refinement in CA3 was impaired in SynCAM 1 KO mice. Mossy fibers make excitatory inputs onto postsynaptic specializations of CA3 pyramidal neurons termed thorny excrescences and these structures were smaller in the absence of SynCAM 1. However, the most prevalent targets of mossy fibers are GABAergic interneurons and SynCAM 1 loss unexpectedly reduced the number of excitatory terminals onto parvalbumin (PV)-positive interneurons in CA3. SynCAM 1 KO mice additionally exhibited lower postsynaptic GluA1 expression in these PV-positive interneurons. These synaptic imbalances in SynCAM 1 KO mice resulted in CA3 disinhibition, in agreement with reduced feedforward inhibition in this network in the absence of SynCAM 1-dependent excitatory drive onto interneurons. In turn, mice lacking SynCAM 1 were impaired in memory tasks involving CA3. Our results support that SynCAM 1 modulates excitatory mossy fiber inputs onto both interneurons and principal neurons in the hippocampal CA3 area to balance network excitability. This study advances our understanding of synapse-organizing mechanisms on two levels. First, the data support that synaptogenic proteins guide connectivity and can function in distinct brain regions even if they are expressed broadly

  14. SynTec Final Technical Report: Synthetic biology for Tailored Enzyme cocktails

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Janine; Teter, Sarah

    Using a novel enzyme screening method inspired by synthetic biology, Novozymes developed new technology under SynTec which allows for more rapidly tailoring of enzyme cocktails. The methodology can be applied to specific feedstocks, and or coupled to address a specific hydrolytic conversion process context. Using combinatorial high throughput screening of libraries of enzyme domains, we can quickly assess which combination of catalytic modules delivers the best performance for a specific condition. To demonstrate the effectiveness of the screening process, we measured performance of the output catalytic cocktail compared to CTec3/HTec3. SynTec benchmark cocktail - blend of Cellic® CTec3 and HTec3.more » The test substrate was - ammonia fiber expansion pretreated corn stover (AFEX™ PCS).CTec3/HTec3 was assayed at the optimal pH and temperature, and also in the absence of any pH adjustment. The new enzyme cocktail discovered under SynTec was assayed in the absence of any pH adjustment and at the optimal temperature. Conversion is delivered by SynTec enzyme at significant dose reduction relative to CTec3/HTec3 at the controlled pH optimum, and without titrant required to maintain pH, which delivers additional cost savings relative to current state of the art process. In this 2.5 year $4M project, the team delivered an experimental cocktail that significantly outperformed CTec3/HTec3 for a specific substrate, and for specific hydrolysis conditions. As a means of comparing performance improvement delivered per research dollar spent, we note that SynTec delivered a similar performance improvement to the previous award, in a shorter time and with fewer resources than for the previously successful DOE project DECREASE, a 3.5 year, $25M project, though this project focused on a different substrate and used different hydrolysis conditions. The newly implemented technology for rapid sourcing of new cellulases and hemicellulases from nature is an example of Novozymes

  15. First morphological and molecular analysis of Eucoleus boehmi like eggs in dogs from Argentina.

    PubMed

    Lavallén, Carla Mariela; Petrigh, Romina Sandra; Fugassa, Martín Horacio; Denegri, Guillermo María; Dopchiz, Marcela Cecilia

    2018-07-01

    The canid parasites Eucoleus aerophilus (syn. Capillaria aerophila) and Eucoleus boehmi (syn. Capillaria boehmi) parasitize the lower and the upper respiratory tract, respectively. Reports and descriptions of these nematodes are scarce in Argentina, possibly due to misdiagnosis of morphologically similar trichuroids eggs, and the lack of knowledge about the species of Eucoleus in this geographical area. Scanning electron microscopy is a useful tool for identification of E. boehmi eggs based on the characteristics of the shell structure which differentiate between species. Molecular analysis complements morphological identification. Until now, there are no studies based on the analysis of E. boehmi eggs in Argentina. The aim of the present work was to study by morphological, morphometric, and molecular analysis, eggs attributable to E. boehmi isolated from dogs naturally infected in Mar del Plata city, Argentina. Eggs isolated from two dog fecal samples were analyzed by light and scanning electron microscopy. A fragment of mitochondrial DNA (mtDNA) of the cytochrome c oxidase subunit I gene (cox1) from eggs was sequenced, and phylogenetic analysis was performed in this study. According to morphological results based on the wall surface ultrastructure, the eggs studied were assigned to E. boehmi. Molecular analysis supported the morphological identification. The divergence of 9-12% with the European isolated could suggest a new geographical genetic variation of E. boehmi, but also question the possible existence of cryptic species. This is the first characterization of E. boehmi eggs in dogs from Argentina.

  16. Lateral assembly of the immunoglobulin protein SynCAM 1 controls its adhesive function and instructs synapse formation.

    PubMed

    Fogel, Adam I; Stagi, Massimiliano; Perez de Arce, Karen; Biederer, Thomas

    2011-09-16

    Synapses are specialized adhesion sites between neurons that are connected by protein complexes spanning the synaptic cleft. These trans-synaptic interactions can organize synapse formation, but their macromolecular properties and effects on synaptic morphology remain incompletely understood. Here, we demonstrate that the synaptic cell adhesion molecule SynCAM 1 self-assembles laterally via its extracellular, membrane-proximal immunoglobulin (Ig) domains 2 and 3. This cis oligomerization generates SynCAM oligomers with increased adhesive capacity and instructs the interactions of this molecule across the nascent and mature synaptic cleft. In immature neurons, cis assembly promotes the adhesive clustering of SynCAM 1 at new axo-dendritic contacts. Interfering with the lateral self-assembly of SynCAM 1 in differentiating neurons strongly impairs its synaptogenic activity. At later stages, the lateral oligomerization of SynCAM 1 restricts synaptic size, indicating that this adhesion molecule contributes to the structural organization of synapses. These results support that lateral interactions assemble SynCAM complexes within the synaptic cleft to promote synapse induction and modulate their structure. These findings provide novel insights into synapse development and the adhesive mechanisms of Ig superfamily members.

  17. Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome.

    PubMed

    Shen, Yue; Wang, Yun; Chen, Tai; Gao, Feng; Gong, Jianhui; Abramczyk, Dariusz; Walker, Roy; Zhao, Hongcui; Chen, Shihong; Liu, Wei; Luo, Yisha; Müller, Carolin A; Paul-Dubois-Taine, Adrien; Alver, Bonnie; Stracquadanio, Giovanni; Mitchell, Leslie A; Luo, Zhouqing; Fan, Yanqun; Zhou, Baojin; Wen, Bo; Tan, Fengji; Wang, Yujia; Zi, Jin; Xie, Zexiong; Li, Bingzhi; Yang, Kun; Richardson, Sarah M; Jiang, Hui; French, Christopher E; Nieduszynski, Conrad A; Koszul, Romain; Marston, Adele L; Yuan, Yingjin; Wang, Jian; Bader, Joel S; Dai, Junbiao; Boeke, Jef D; Xu, Xun; Cai, Yizhi; Yang, Huanming

    2017-03-10

    Here, we report the successful design, construction, and characterization of a 770-kilobase synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels-including phenomics, transcriptomics, proteomics, chromosome segregation, and replication analysis-to provide a thorough and comprehensive analysis of a synthetic chromosome. Our Trans-Omics analyses reveal a modest but potentially relevant pervasive up-regulation of translational machinery observed in synII, mainly caused by the deletion of 13 transfer RNAs. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP -mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the high-osmolarity glycerol response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain. Copyright © 2017, American Association for the Advancement of Science.

  18. The Synaptic Cell Adhesion Molecule, SynCAM1, Mediates Astrocyte-to-Astrocyte and Astrocyte-to-GnRH Neuron Adhesiveness in the Mouse Hypothalamus

    PubMed Central

    Sandau, Ursula S.; Mungenast, Alison E.; McCarthy, Jack; Biederer, Thomas; Corfas, Gabriel

    2011-01-01

    We previously identified synaptic cell adhesion molecule 1 (SynCAM1) as a component of a genetic network involved in the hypothalamic control of female puberty. Although it is well established that SynCAM1 is a synaptic adhesion molecule, its contribution to hypothalamic function is unknown. Here we show that, in addition to the expected neuronal localization illustrated by its presence in GnRH neurons, SynCAM1 is expressed in hypothalamic astrocytes. Cell adhesion assays indicated that SynCAM is recognized by both GnRH neurons and astrocytes as an adhesive partner and promotes cell-cell adhesiveness via homophilic, extracellular domain-mediated interactions. Alternative splicing of the SynCAM1 primary mRNA transcript yields four mRNAs encoding membrane-spanning SynCAM1 isoforms. Variants 1 and 4 are predicted to be both N and O glycosylated. Hypothalamic astrocytes and GnRH-producing GT1-7 cells express mainly isoform 4 mRNA, and sequential N- and O-deglycosylation of proteins extracted from these cells yields progressively smaller SynCAM1 species, indicating that isoform 4 is the predominant SynCAM1 variant expressed in astrocytes and GT1-7 cells. Neither cell type expresses the products of two other SynCAM genes (SynCAM2 and SynCAM3), suggesting that SynCAM-mediated astrocyte-astrocyte and astrocyte-GnRH neuron adhesiveness is mostly mediated by SynCAM1 homophilic interactions. When erbB4 receptor function is disrupted in astrocytes, via transgenic expression of a dominant-negative erbB4 receptor form, SynCAM1-mediated adhesiveness is severely compromised. Conversely, SynCAM1 adhesive behavior is rapidly, but transiently, enhanced in astrocytes by ligand-dependent activation of erbB4 receptors, suggesting that erbB4-mediated events affecting SynCAM1 function contribute to regulate astrocyte adhesive communication. PMID:21486931

  19. BrisSynBio: a BBSRC/EPSRC-funded Synthetic Biology Research Centre.

    PubMed

    Sedgley, Kathleen R; Race, Paul R; Woolfson, Derek N

    2016-06-15

    BrisSynBio is the Bristol-based Biotechnology and Biological Sciences Research Council (BBSRC)/Engineering and Physical Sciences Research Council (EPSRC)-funded Synthetic Biology Research Centre. It is one of six such Centres in the U.K. BrisSynBio's emphasis is on rational and predictive bimolecular modelling, design and engineering in the context of synthetic biology. It trains the next generation of synthetic biologists in these approaches, to facilitate translation of fundamental synthetic biology research to industry and the clinic, and to do this within an innovative and responsible research framework. © 2016 The Author(s).

  20. Far-Infrared Spectroscopy of Syn-Vinyl Alcohol

    NASA Astrophysics Data System (ADS)

    Raston, Paul; Bunn, Hayley

    2016-06-01

    Vinyl alcohol has been extensively studied in both the microwave and mid-IR spectral regions, where 9 out of 15 vibrational modes have been identified. Here we present the first far-IR spectrum of vinyl alcohol, collected below 700 wn at the Australian Synchrotron. The high resolution (0.001 wn) spectrum reveals the νb{11} and νb{15} fundamentals of syn-vinyl alcohol at 489 wn and 407 wn, in addition to two hot bands of the νb{15} mode at 369 wn and 323 wn. High J transitions in the R-branch of the νb{15} band were found to be perturbed by an a-axis Coriolis interaction with the nearby νb{11} state. The νb{15} torsional mode of syn-vinyl alcohol was fit using a Watson's A-reduced Hamiltonian to yield rotational, centrifugal distortion, and Coriolis coupling parameters. S. Saito, Chem. Phys. Lett. 42, 3 (1976) M. Rodler et al., J. Am. Chem. Soc. 106, 4029 (1948) Y. Koga et al., J. Mol. Spec. 145, 315 (1991) D-L. Joo et al., J. Mol. Spec. 197, 68 (1999)

  1. Syn- and anti-conformations of 5'-deoxy- and 5'-O-methyl-uridine 2',3'-cyclic monophosphate.

    PubMed

    Grabarkiewicz, Tomasz; Hoffmann, Marcin

    2006-01-01

    Two uridine 2',3'-cyclic monophosphate (cUMP) derivatives, 5'-deoxy (DcUMP) and 5'-O-methyl (McUMP), were studied by means of quantum chemical methods. Aqueous solvent effects were estimated based on the isodensity-surface polarized-continuum model (IPCM). Gas phase calculations revealed only slight energy differences between the syn- and anti-conformers of both compounds: the relative energies of the syn-structure are -0.9 and 0.2 kcal mol(-1) for DcUMP and McUMP, respectively. According to the results from the IPCM calculations, however, both syn-conformers become about 14 kcal mol(-1) more stable in aqueous solution than their corresponding anti-structures. Additionally, the effects of a countercation and protonation on DcUMP were studied, revealing that the syn-structure is also favored over the anti-one for these systems.

  2. Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of Schizophrenia.

    PubMed

    Guo, Xiaochuan; Hamilton, Peter J; Reish, Nicholas J; Sweatt, J David; Miller, Courtney A; Rumbaugh, Gavin

    2009-06-01

    Abnormal function of NMDA receptors is believed to be a contributing factor to the pathophysiology of schizophrenia. NMDAR subunits and postsynaptic-interacting proteins of these channels are abnormally expressed in some patients with this illness. In mice, reduced NMDAR expression leads to behaviors analogous to symptoms of schizophrenia, but reports of animals with mutations in core postsynaptic density proteins having similar a phenotype have yet to be reported. Here we show that reduced expression of the neuronal RasGAP and NMDAR-associated protein, SynGAP, results in abnormal behaviors strikingly similar to that reported in mice with reduced NMDAR function. SynGAP mutant mice exhibited nonhabituating and persistent hyperactivity that was ameliorated by the antipsychotic clozapine. An NMDAR antagonist, MK-801, induced hyperactivity in normal mice but SynGAP mutants were less responsive, suggesting that NMDAR hypofunction contributes to this behavioral abnormality. SynGAP mutants exhibited enhanced startle reactivity and impaired sensory-motor gating. These mice also displayed a complete lack of social memory and a propensity toward social isolation. Finally, SynGAP mutants had deficits in cued fear conditioning and working memory, indicating abnormal function of circuits that control emotion and choice. Our results demonstrate that SynGAP mutant mice have gross neurological deficits similar to other mouse models of schizophrenia. Because SynGAP interacts with NMDARs, and the signaling activity of this protein is regulated by these channels, our data in dicate that SynGAP lies downstream of NMDARs and is a required intermediate for normal neural circuit function and behavior. Taken together, these data support the idea that schizophrenia may arise from abnormal signaling pathways that are mediated by NMDA receptors.

  3. Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.

    PubMed

    Muhia, Mary; Yee, Benjamin K; Feldon, Joram; Markopoulos, Foivos; Knuesel, Irene

    2010-02-01

    The brain-specific Ras/Rap-GTPase activating protein (SynGAP) is a prime candidate linking N-methyl-d-aspartate receptors to the regulation of the ERK/MAP kinase signalling cascade, suggested to be essential for experience-dependent synaptic plasticity. Here, we evaluated the behavioural phenotype of SynGAP heterozygous knockout mice (SG(+/-)), expressing roughly half the normal levels of SynGAP. In the cognitive domain, SG(+/-) mice demonstrated severe working and reference memory deficits in the radial arm maze task, a mild impairment early in the transfer test of the water maze task, and a deficiency in spontaneous alternation in an elevated T-maze. In the non-cognitive domain, SG(+/-) mice were hyperactive in the open field and appeared less anxious in the elevated plus maze test. In contrast, object recognition memory performance was not impaired in SG(+/-) mice. The reduction in SynGAP thus resulted in multiple behavioural traits suggestive of aberrant cognitive and non-cognitive processes normally mediated by the hippocampus. Immunohistochemical evaluation further revealed a significant reduction in calbindin-positive interneurons in the hippocampus and doublecortin-positive neurons in the dentate gyrus of adult SG(+/-) mice. Heterozygous constitutive deletion of SynGAP is therefore associated with notable behavioural as well as morphological phenotypes indicative of hippocampal dysfunction. Any suggestion of a possible causal link between them however remains a matter for further investigation.

  4. Immune responses induced by co-infection with Capillaria hepatica in Clonorchis sinensis-infected rats.

    PubMed

    Moon, E-K; Lee, S-H; Goo, T W; Quan, F-S

    2018-07-01

    Clonorchis sinensis and Capillaria hepatica are zoonotic parasites that mainly infect the liver and cause serious liver disorders. However, immunological parameters induced by co-infection with these parasites remain unknown. In this study, for the first time, we investigated immunological profiles induced by co-infection with C. hepatica (CH) in C. sinensis (CS)-infected rats (Sprague-Dawley). Rats were infected primarily with 50 metacercariae of C. sinensis; 4 weeks later, they were subsequently infected with 1000 infective C. hepatica eggs. Significantly higher levels of C. sinensis- or C. hepatica-specific IgG antibodies were found in the sera of rats. Interestingly, no cross-reacting antibody was observed between C. sinensis and C. hepatica infections. Significantly raised eosinophil levels were found in the blood of C. sinensis/C. hepatica co-infected rats (CS + CH) compared to the blood of rats infected singly with C. sinensis. Co-infected rats showed significantly higher levels of lymphocyte proliferation and cytokine production compared to a single C. sinensis infection. The worm burden of C. sinensis was significantly reduced in co-infected rats compared to the single C. sinensis infection. These results indicate that the eosinophils, lymphocyte proliferation and cytokine production induced by subsequent infection with C. hepatica in C. sinensis-infected rats might contribute to the observed C. sinensis worm reduction.

  5. Stereoselective bioaccumulation of syn- and anti-Dechlorane plus isomers in different tissues of common carp (Cyprinus carpio).

    PubMed

    Tang, Bin; Luo, Xiao-Jun; Huang, Chen-Chen; Sun, Run-Xia; Wang, Tao; Zeng, Yan-Hong; Mai, Bi-Xian

    2018-03-01

    Common carps (Cyprinus carpio) were exposed to syn- and anti-Dechlorane Plus (DP) isomers to investigate absorption, tissue distribution, and stereoselective bioaccumulation of DP isomers. The absorption efficiencies of anti-DP in the gastrointestinal system were higher than those of syn-DP. A linear accumulation was found for both isomers in all fish tissues except for serum; and the liver and gill exhibited the highest and lowest DP assimilation efficiency, respectively. The elimination of DP isomers in all tissues followed first-order kinetics, with the fastest depuration rate occurring in the liver and serum. The biomagnification factors (BMFs) of both isomers were less than one in all tissues, except for serum. Anti-DP was preferably accumulated in the liver, gill, and serum, whereas syn-DP was selectively accumulated in the carcass and gastrointestinal tract. As a whole, fish did not show selective accumulation of the syn- or anti-DP isomer in the uptake stage, whereas a selective accumulation of syn-DP in fish was observed during the depuration period, which could be due to a selective excretion of anti-DP. Metabolism cannot be ruled out as a possible reason considering the high f anti values and the high elimination rate of DPs in the liver. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Evidence for large-scale imbrication during Eocene syn-orogenic exhumation of the Hellenic subduction channel (Cyclades, Greece)

    NASA Astrophysics Data System (ADS)

    Grasemann, Bernhard; Huet, Benjamin; Schneider, David; Rice, Hugh; Lemonnier, Nicolas; Tschegg, Cornelius

    2017-04-01

    In the Cyclades, Miocene post-orogenic back-arc extension overprinted the exhumed syn- orogenic Eocene subduction channel. Whereas the exact geometry and kinematics of the syn-orogenic exhumation are still controversial, but must have involved a floor thrust and an apparent normal fault at the roof, the post-orogenic extension, leading to the exhumation of Cordilleran-type metamorphic core complexes, is well constrained by several major detachment systems. On the island of Milos, which is part of the South Aegean Volcanic Arc, minor outcrops of schist occur. New data indicate that these witnessed Eocene blueschist facies metamorphism at 8.5 kbar and 400°C, but escaped the Miocene extensional overprint, as they lie in the hanging wall of the West Cycladic Detachment System. In contrast, eclogite pebbles in "Green Lahars" on Milos yield metamorphic conditions of 19.5 kbar at 550°C. Both high-pressure units belong to the Cycladic Blueschist Unit and can only have been juxtaposed by thrusting. This indicates that two nappes, the newly defined Cycladic Blueschist Nappe and the overlying Cycladic Eclogite Nappe, both comprising rocks of the Cycladic Blueschist Unit, exist on Milos. These nappes probably also form the other Cycladic islands, separated by a syn-orogenic thrust, which we name the Trans Cycladic Thrust. The Trans Cycladic Thrust, which traces the orientation of the syn-orogenic exhumation channel, is partly offset by the post-orogenic Miocene extensional detachment systems. As a result of the Mid- to Late Miocene clockwise crustal block rotation, the syn-orogenic channel, and hence the Trans Cycladic Thrust, bends through 90° at Milos, changing from a W-E trending to a N-S trending extrusion-related stretching lineation. Restoration of the Miocene block-rotation and extension results in syn-orogenic thrusting kinematics (top-SSW) in the Cycladic Blueschist Nappe and along the Trans Cycladic Thrust and syn-orogenic apparent normal faulting kinematics (top

  7. Infrared identification of the Criegee intermediates syn- and anti-CH3CHOO, and their distinct conformation-dependent reactivity

    PubMed Central

    Lin, Hui-Yu; Huang, Yu-Hsuan; Wang, Xiaohong; Bowman, Joel M.; Nishimura, Yoshifumi; Witek, Henryk A.; Lee, Yuan-Pern

    2015-01-01

    The Criegee intermediates are carbonyl oxides that play critical roles in ozonolysis of alkenes in the atmosphere. So far, the mid-infrared spectrum of only the simplest Criegee intermediate CH2OO has been reported. Methyl substitution of CH2OO produces two conformers of CH3CHOO and consequently complicates the infrared spectrum. Here we report the transient infrared spectrum of syn- and anti-CH3CHOO, produced from CH3CHI + O2 in a flow reactor, using a step-scan Fourier-transform spectrometer. Guided and supported by high-level full-dimensional quantum calculations, rotational contours of the four observed bands are simulated successfully and provide definitive identification of both conformers. Furthermore, anti-CH3CHOO shows a reactivity greater than syn-CH3CHOO towards NO/NO2; at the later period of reaction, the spectrum can be simulated with only syn-CH3CHOO. Without NO/NO2, anti-CH3CHOO also decays much faster than syn-CH3CHOO. The direct infrared detection of syn- and anti-CH3CHOO should prove useful for field measurements and laboratory investigations of the Criegee mechanism. PMID:25959902

  8. Sensitivity analyses of exposure estimates from a quantitative job-exposure matrix (SYN-JEM) for use in community-based studies.

    PubMed

    Peters, Susan; Kromhout, Hans; Portengen, Lützen; Olsson, Ann; Kendzia, Benjamin; Vincent, Raymond; Savary, Barbara; Lavoué, Jérôme; Cavallo, Domenico; Cattaneo, Andrea; Mirabelli, Dario; Plato, Nils; Fevotte, Joelle; Pesch, Beate; Brüning, Thomas; Straif, Kurt; Vermeulen, Roel

    2013-01-01

    We describe the elaboration and sensitivity analyses of a quantitative job-exposure matrix (SYN-JEM) for respirable crystalline silica (RCS). The aim was to gain insight into the robustness of the SYN-JEM RCS estimates based on critical decisions taken in the elaboration process. SYN-JEM for RCS exposure consists of three axes (job, region, and year) based on estimates derived from a previously developed statistical model. To elaborate SYN-JEM, several decisions were taken: i.e. the application of (i) a single time trend; (ii) region-specific adjustments in RCS exposure; and (iii) a prior job-specific exposure level (by the semi-quantitative DOM-JEM), with an override of 0 mg/m(3) for jobs a priori defined as non-exposed. Furthermore, we assumed that exposure levels reached a ceiling in 1960 and remained constant prior to this date. We applied SYN-JEM to the occupational histories of subjects from a large international pooled community-based case-control study. Cumulative exposure levels derived with SYN-JEM were compared with those from alternative models, described by Pearson correlation ((Rp)) and differences in unit of exposure (mg/m(3)-year). Alternative models concerned changes in application of job- and region-specific estimates and exposure ceiling, and omitting the a priori exposure ranking. Cumulative exposure levels for the study subjects ranged from 0.01 to 60 mg/m(3)-years, with a median of 1.76 mg/m(3)-years. Exposure levels derived from SYN-JEM and alternative models were overall highly correlated (R(p) > 0.90), although somewhat lower when omitting the region estimate ((Rp) = 0.80) or not taking into account the assigned semi-quantitative exposure level (R(p) = 0.65). Modification of the time trend (i.e. exposure ceiling at 1950 or 1970, or assuming a decline before 1960) caused the largest changes in absolute exposure levels (26-33% difference), but without changing the relative ranking ((Rp) = 0.99). Exposure estimates derived from SYN

  9. SynTrack: DNA Assembly Workflow Management (SynTrack) v2.0.1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    MENG, XIANWEI; SIMIRENKO, LISA

    2016-12-01

    SynTrack is a dynamic, workflow-driven data management system that tracks the DNA build process: Management of the hierarchical relationships of the DNA fragments; Monitoring of process tasks for the assembly of multiple DNA fragments into final constructs; Creations of vendor order forms with selectable building blocks. Organizing plate layouts barcodes for vendor/pcr/fusion/chewback/bioassay/glycerol/master plate maps (default/condensed); Creating or updating Pre-Assembly/Assembly process workflows with selected building blocks; Generating Echo pooling instructions based on plate maps; Tracking of building block orders, received and final assembled for delivering; Bulk updating of colony or PCR amplification information, fusion PCR and chewback results; Updating with QA/QCmore » outcome with .csv & .xlsx template files; Re-work assembly workflow enabled before and after sequencing validation; and Tracking of plate/well data changes and status updates and reporting of master plate status with QC outcomes.« less

  10. MedSynDiKATe--design considerations for an ontology-based medical text understanding system.

    PubMed Central

    Hahn, U.; Romacker, M.; Schulz, S.

    2000-01-01

    MedSynDiKATe is a natural language processor for automatically acquiring knowledge from medical finding reports. The content of these documents is transferred to formal representation structures which constitute a corresponding text knowledge base. The general system architecture we present integrates requirements from the analysis of single sentences, as well as those of referentially linked sentences forming cohesive texts. The strong demands MedSynDiKATe poses to the availability of expressive knowledge sources are accounted for by two alternative approaches to (semi)automatic ontology engineering. PMID:11079899

  11. 40 CFR 174.529 - Bacillus thuringiensis modified Cry1Ab protein as identified under OECD Unique Identifier SYN...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... protein as identified under OECD Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement... Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement of a tolerance. Residues of... exempt from the requirement of a tolerance when used as a plant-incorporated protectant in cotton; cotton...

  12. 40 CFR 174.529 - Bacillus thuringiensis modified Cry1Ab protein as identified under OECD Unique Identifier SYN...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... protein as identified under OECD Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement... Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement of a tolerance. Residues of... exempt from the requirement of a tolerance when used as a plant-incorporated protectant in cotton; cotton...

  13. 40 CFR 174.529 - Bacillus thuringiensis modified Cry1Ab protein as identified under OECD Unique Identifier SYN...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... protein as identified under OECD Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement... Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement of a tolerance. Residues of... exempt from the requirement of a tolerance when used as a plant-incorporated protectant in cotton; cotton...

  14. 40 CFR 174.529 - Bacillus thuringiensis modified Cry1Ab protein as identified under OECD Unique Identifier SYN...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... protein as identified under OECD Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement... Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement of a tolerance. Residues of... exempt from the requirement of a tolerance when used as a plant-incorporated protectant in cotton; cotton...

  15. 40 CFR 174.529 - Bacillus thuringiensis modified Cry1Ab protein as identified under OECD Unique Identifier SYN...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... protein as identified under OECD Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement... Unique Identifier SYN-IR67B-1 in cotton; exemption from the requirement of a tolerance. Residues of... exempt from the requirement of a tolerance when used as a plant-incorporated protectant in cotton; cotton...

  16. Nonclinical Safety Assessment of SYN-004: An Oral β-lactamase for the Protection of the Gut Microbiome From Disruption by Biliary-Excreted, Intravenously Administered Antibiotics.

    PubMed

    Kokai-Kun, John F; Bristol, J Andrew; Setser, John; Schlosser, Michael

    2016-05-01

    SYN-004 is a first in class, recombinant β-lactamase that degrades β-lactam antibiotics and has been formulated to be administered orally to patients receiving intravenous β-lactam antibiotics including cephalosporins. SYN-004 is intended to degrade unmetabolized antibiotics excreted into the intestines and thus has the potential to protect the gut microbiome from disruption by these antibiotics. Protection of the gut microbiome is expected to protect against opportunistic enteric infections such as Clostridium difficile infection as well as antibiotic-associated diarrhea. In order to demonstrate that oral SYN-004 is safe for human clinical trials, 2 Good Laboratory Practice-compliant toxicity studies were conducted in Beagle dogs. In both studies, SYN-004 was administered orally 3 times per day up to the maximum tolerated dose of the formulation. In the first study, doses of SYN-004 administered over 28 days were safe and well tolerated in dogs with the no-observed-adverse-effect level at the high dose of 57 mg/kg/day. Systemic absorption of SYN-004 was minimal and sporadic and showed no accumulation during the study. In the second study, doses up to 57 mg/kg/day were administered to dogs in combination with an intravenous dose of ceftriaxone (300 mg/kg) given once per day for 14 days. Coadministration of oral SYN-004 with intravenous ceftriaxone was safe and well tolerated, with SYN-004 having no noticeable effect on the plasma pharmacokinetics of ceftriaxone. These preclinical studies demonstrate that SYN-004 is well tolerated and, when coadministered with ceftriaxone, does not interfere with its systemic pharmacokinetics. These data supported advancing SYN-004 into human clinical trials. © The Author(s) 2015.

  17. Randomized controlled trial of Syn-Ergel and an active placebo in the treatment of heartburn of pregnancy.

    PubMed

    Shaw, R W

    1978-01-01

    A randomized controlled trial was performed to study the efficacy of Syn-Ergel with an active placebo in the treatment of heartburn of pregnancy in ninety-two patients completing 7 days of therapy. Syn-Ergel was significantly better (p less than 0.001) in all groups of pre-treatment pain severity in relieving the symptoms, and had a longer duration of action, than the active placebo. Complete relief of pain was achieved in 79.5% of Syn-Ergel treatments with a further 10% of treatments resulting in marked easing of discomfort at 1 hour following administration. The corresponding figures for the 'active placebo' were 56% and 20%. The combination of an antacid and a protective mucosal coating agent would appear to be a useful approach in the treatment of heartburn of pregnacy.

  18. Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection.

    PubMed

    Kaleko, Michael; Bristol, J Andrew; Hubert, Steven; Parsley, Todd; Widmer, Giovanni; Tzipori, Saul; Subramanian, Poorani; Hasan, Nur; Koski, Perrti; Kokai-Kun, John; Sliman, Joseph; Jones, Annie; Connelly, Sheila

    2016-10-01

    The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta-lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. Here we present the preclinical development and early clinical studies of the beta-lactamase enzymes, P3A, currently referred to as SYN-004, and its precursor, P1A. Both P1A and SYN-004 were designed as orally-delivered, non-systemically available therapeutics for use with intravenous beta-lactam antibiotics. SYN-004 was engineered from P1A, a beta-lactamase isolated from Bacillus licheniformis, to broaden its antibiotic degradation profile. SYN-004 efficiently hydrolyses penicillins and cephalosporins, the most widely used IV beta-lactam antibiotics. In animal studies, SYN-004 degraded ceftriaxone in the GI tract of dogs and protected the microbiome of pigs from ceftriaxone-induced changes. Phase I clinical studies demonstrated SYN-004 safety and tolerability. Phase 2 studies are in progress to assess the utility of SYN-004 for the prevention of antibiotic-associated diarrhea and Clostridium difficile disease. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Structural development of the onshore Otway passive margin (Australia): the interaction of rotating syn-sedimentary faults

    NASA Astrophysics Data System (ADS)

    Tanner, David C.; Ziesch, Jennifer; Krawczyk, Charlotte M.

    2017-04-01

    Within the context of long-term CO2 storage integrity, we interpreted the faults within the 2.2 km thick, syn-rift, Late Cretaceous to Recent sediments below the CO2CRC Otway Project site in Australia using a detailed interpretation of a 3-D reflection seismic cube (32.3 km×14.35 km × 4100 ms TWT). All the faults in the onshore Otway passive margin basin in this area were active to varying degrees during sedimentation, between ca. 120 and 50 Ma, before they died out. From analysis of fault juxtaposition and fault tip-line propagation maps, as well as analysis of individual stratigraphic thickness maps, we determine the direction and incremental amount of syn-sedimentary movement on each fault. Thickening of the hanging-walls of the faults occurred, as is typical for syn-sedimentary faults. However, we also determine that substantial local footwall thinning took place. Although the syn-sedimentary behaviour of the faults was constantly maintained until 50 Ma, there were two main phases of footwall thinning, separated by a quiescent phase. We postulate that these phases of footwall thinning represent rotation of the fault blocks that correlate with prograding sediment pulses within the passive margin. The rotation of the fault blocks occurred simultaneously, i.e., they could only rotate if they interacted.

  20. Discovery of syn-/anti-cocaine-N-oxide diastereomers in unwashed postmortem hair via LC-MS-MS.

    PubMed

    Marsh, Christine M; Crawley, Lindsey R; Himes, Sarah K; Aranda, Roman; Miller, Mark L

    2014-01-01

    The discovery of two cocaine-N-oxide (CNO) diastereomers, syn- and anti-CNO, is reported for the first time. Prior to this study, only one structural form of CNO was known to exist and has not been analyzed in hair before. CNO is a metabolite of cocaine (COC) and may be considered as an additional biomarker of COC use, along with other known COC metabolites. The analysis of COC in hair for forensic applications is under scrutiny due to the possibility of external contamination. A qualitative liquid chromatography-tandem mass spectrometry method was developed, validated and applied to unwashed postmortem hair samples from drug users. The limit of detection in hair was 8 pg/mg (using 10 mg of unwashed hair) for each CNO diastereomer. The presence of both syn- and anti-forms of CNO was verified in vivo using hair samples collected from known COC-using individuals. Due to the low levels of CNO, it will not always be detectable in COC user hair. In the hair samples analyzed, syn-CNO was detected in more samples than anti-CNO. The stereoselective N-oxidation of COC which favors syn-CNO could have a diagnostic value for COC ingestion determination in hair analysis. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Quantification of indirect pathway inhibition by the adenosine A2a antagonist SYN115 in Parkinson disease.

    PubMed

    Black, Kevin J; Koller, Jonathan M; Campbell, Meghan C; Gusnard, Debra A; Bandak, Stephen I

    2010-12-01

    Adenosine A(2a) receptor antagonists reduce symptom severity in Parkinson disease (PD) and animal models. Rodent studies support the hypothesis that A(2a) antagonists produce this benefit by reducing the inhibitory output of the basal ganglia indirect pathway. One way to test this hypothesis in humans is to quantify regional pharmacodynamic responses with cerebral blood flow (CBF) imaging. That approach has also been proposed as a tool to accelerate pharmaceutical dose finding, but has not yet been applied in humans to drugs in development. We successfully addressed both these aims with a perfusion magnetic resonance imaging (MRI) study of the novel adenosine A(2a) antagonist SYN115. During a randomized, double-blind, placebo-controlled, crossover study in 21 PD patients on levodopa but no agonists, we acquired pulsed arterial spin labeling MRI at the end of each treatment period. SYN115 produced a highly significant decrease in thalamic CBF, consistent with reduced pallidothalamic inhibition via the indirect pathway. Similar decreases occurred in cortical regions whose activity decreases with increased alertness and externally focused attention, consistent with decreased self-reported sleepiness on SYN115. Remarkably, we also derived quantitative pharmacodynamic parameters from the CBF responses to SYN115. These results suggested that the doses tested were on the low end of the effective dose range, consistent with clinical data reported separately. We conclude that (1) SYN115 enters the brain and exerts dose-dependent regional effects, (2) the most prominent of these effects is consistent with deactivation of the indirect pathway as predicted by preclinical studies; and (3) perfusion MRI can provide rapid, quantitative, clinically relevant dose-finding information for pharmaceutical development.

  2. Quantification of indirect pathway inhibition by the adenosine A2a antagonist SYN115 in Parkinson disease

    PubMed Central

    Black, Kevin J.; Koller, Jonathan M.; Campbell, Meghan C.; Gusnard, Debra A.; Bandak, Stephen I.

    2010-01-01

    Adenosine A2a receptor antagonists reduce symptom severity in Parkinson disease (PD) and animal models. Rodent studies support the hypothesis that A2a antagonists produce this benefit by reducing the inhibitory output of the basal ganglia indirect pathway. One way to test this hypothesis in humans is to quantify regional pharmacodynamic responses with cerebral blood flow (CBF) imaging. That approach has also been proposed as a tool to accelerate pharmaceutical dose-finding, but has not yet been applied in humans to drugs in development. We successfully addressed both these aims with a perfusion MRI study of the novel adenosine A2a antagonist SYN115. During a randomized, double-blind, placebo-controlled, crossover study in 21 PD patients on levodopa but no agonists, we acquired pulsed arterial spin labeling MRI at the end of each treatment period. SYN115 produced a highly significant decrease in thalamic CBF, consistent with reduced pallidothalamic inhibition via the indirect pathway. Similar decreases occurred in cortical regions whose activity decreases with increased alertness and externally-focused attention, consistent with decreased self-reported sleepiness on SYN115. Remarkably, we also derived quantitative pharmacodynamic parameters from the CBF responses to SYN115. These results suggested that the doses tested were on the low end of the effective dose range, consistent with clinical data reported separately. We conclude that (1) SYN115 enters the brain and exerts dose-dependent regional effects, (2) the most prominent of these effects is consistent with deactivation of the indirect pathway as predicted by preclinical studies; and (3) perfusion MRI can provide rapid, quantitative, clinically relevant dose-finding information for pharmaceutical development. PMID:21123574

  3. Assigning the stereochemistry of syn and anti β-trimethylsiloxy-α-trimethylsilyl alkanoic acid silyl esters using GIAO 1H NMR chemical shift calculations

    NASA Astrophysics Data System (ADS)

    Hadj Mohamed, Slim; Trabelsi, Mahmoud; Champagne, Benoît

    2017-08-01

    The stereostructure of β-trimethylsiloxy-α-trimethylsilyl alkanoic acid silyl esters synthesized by Bellassoued et al. [J. Org. Chem. 2001, 66, 5054-5057] using Mukaiyama aldol reaction has been reassigned using density functional theory NMR 1H chemical shifts calculations. It is now concluded that the major diastereoisomer is syn and the minor is anti. Within this assignment, for all silyl esters, δHa(anti) > δHa(syn), δHb(anti) < δHb(syn), and 3JHa-Hb (anti) > 3JHa-Hb (syn). Since the experimental assignment was based on the stereostructure (E/Z) of the cinnamic acid obtained by elimination of trimethylsilyl 3-phenyl-3-(trimethylsiloxy)-2-(trimethylsilyl)propanoate in the presence of TiCl4 and on the assumption that this elimination is anti stereospecific in acidic medium, one arrives at the conclusion that the elimination of syn and anti β-trimethylsiloxy-α-trimethylsilyl alkanoic acid silyl esters is not anti stereospecific.

  4. A new concept of Absoloniella (=Ruffodytes syn. n.) for five blind Mediterranean species (Coleoptera: Brachyceridae: Erirhininae).

    PubMed

    Grebennikov, Vasily V

    2014-09-22

    A hundred year-long taxonomic ambiguity surrounding two mysterious species originally described as Caulomorphus reitteri Müller, 1912 and Absoloniella cylindrica Formánek, 1913, both known from single specimens believed to be lost, is resolved. This is achieved by designation of their neotypes based on the same specimen collected together, and considered conspecific, with the holotype of Ruffodytes hellenicus Osella, 1973, the latter the type of the genus Ruffodytes Osella, 1973. This action triggers the following nomenclatorial and taxonomic changes: (1) the generic name Ruffodytes Osella, 1973 syn. n. is a junior subjective synonym of Absoloniella Formánek, 1913; (2) the names cylindrica syn. n. and hellenica syn. n. are junior objective and subjective synonyms, respectively, of the name reitteri for the species Absoloniella reitteri (Müller, 1912); (3) the genus Absoloniella currently comprises five species: A. reitteri (Müller, 1912), A. italica (Osella, 1976) comb. n., A. pacei (Osella, 1976) comb. n., A. servadeii (Osella, 1982) and A. nitidipennis (Osella, 1989) comb. n. Puzzling distribution of blind and wingless Mediterranean Absoloniella is briefly discussed.

  5. Capoeta damascina (Valenciennes, 1842), a new host of Contracaecum sp. and Capillaria sp. (Nematoda) from the Kor River Basin, southwestern Iran

    PubMed Central

    Gholami, Zeinab; Rahimi, Mohammad Taghi; Kia, Eshrat Beigom; Esmaeili, Hamid Reza; Mobedi, Iraj

    2014-01-01

    Objective To investigate the parasitic infection status of cyprinid fish, Capoeta damascina in Gomban spring-stream, Kor River Basin, Fars Province, southwestern Iran. Methods A total of 12 cyprinid fish (7 females and 5 males) were collected from Gomban spring-stream, Kor River Basin, Fars Province, southwestern Iran. The collected fish were dissected carefully and their internal organs such as liver, gonad, muscle, abdominal lobes, whole viscera and digestive tract were surveyed parasitologically. Results One female cyprinid fish out of 12 fish was infected with three nematodes. Two nematodes (larvae) were identified as Contracaecum sp. which were attached firmly to the outer part of intestine and another adult helminth was recognized as Capillaria sp. which was recovered from digestive content. Conclusions This study is the first record indicating that cyprinid fish acts as a new host for recovered nematodes. Further helminthological investigations are highly recommended in different parts of Iran in order to expand our knowledge about helmintic parasites of cyprinid fish and their role in transmission of diseases to human and animal. PMID:25183068

  6. Probable hepatic capillariosis and hydatidosis in an adolescent from the late Roman period buried in Amiens (France).

    PubMed

    Mowlavi, Gholamreza; Kacki, Sacha; Dupouy-Camet, Jean; Mobedi, Iraj; Makki, Mahsasadat; Harandi, Majid Fasihi; Naddaf, Saied Reza

    2014-01-01

    Two calcified objects recovered from a 3rd to 4th-century grave of an adolescent in Amiens (Northern France) were identified as probable hydatid cysts. By using thin-section petrographic techniques, probable Calodium hepaticum (syn. Capillaria hepatica) eggs were identified in the wall of the cysts. Human hepatic capillariosis has not been reported from archaeological material so far, but could be expected given the poor level of environmental hygiene prevalent in this period. Identification of tissue-dwelling parasites such as C. hepaticum in archaeological remains is particularly dependent on preservation conditions and taphonomic changes and should be interpreted with caution due to morphological similarities with Trichuris sp. eggs. © G. Mowlavi et al., published by EDP Sciences, 2014.

  7. Genome Sequence, Structural Proteins, and Capsid Organization of the Cyanophage Syn5: A “Horned” Bacteriophage of Marine Synechococcus

    PubMed Central

    Pope, Welkin H.; Weigele, Peter R.; Chang, Juan; Pedulla, Marisa L.; Ford, Michael E.; Houtz, Jennifer M.; Jiang, Wen; Chiu, Wah; Hatfull, Graham F.; Hendrix, Roger W.; King, Jonathan

    2010-01-01

    Marine Synechococcus spp and marine Prochlorococcus spp are numerically dominant photoautotrophs in the open oceans and contributors to the global carbon cycle. Syn5 is a short-tailed cyanophage isolated from the Sargasso Sea on Synechococcus strain WH8109. Syn5 has been grown in WH8109 to high titer in the laboratory and purified and concentrated retaining infectivity. Genome sequencing and annotation of Syn5 revealed that the linear genome is 46,214bp with a 237bp terminal direct repeat. Sixty-one open reading frames (ORFs) were identified. Based on genomic organization and sequence similarity to known protein sequences within GenBank, Syn5 shares features with T7-like phages. The presence of a putative integrase suggests access to a temperate life-cycle. Assignment of eleven ORFs to structural proteins found within the phage virion was confirmed by mass-spectrometry and N-terminal sequencing. Eight of these identified structural proteins exhibited amino acid sequence similarity to enteric phage proteins. The remaining three virion proteins did not resemble any known phage sequences in GenBank as of August 2006. Cryoelectron micrographs of purified Syn5 virions revealed that the capsid has a single “horn”, a novel fibrous structure protruding from the opposing end of the capsid from the tail of the virion. The tail appendage displayed an apparent three-fold rather than six-fold symmetry. An 18Å-resolution icosahedral reconstruction of the capsid revealed a T=7 lattice, but with an unusual pattern of surface knobs. This phage/host system should allow detailed investigation of the physiology and biochemistry of phage propagation in marine photosynthetic bacteria. PMID:17383677

  8. Does the tautomeric status of the adenine bases change upon the dissociation of the A*·A(syn) Topal-Fresco DNA mismatch? A combined QM and QTAIM atomistic insight.

    PubMed

    Brovarets', Ol'ha O; Zhurakivsky, Roman O; Hovorun, Dmytro M

    2014-02-28

    We have scrupulously explored the tautomerisation mechanism via the double proton transfer of the A*·A(syn) Topal-Fresco base mispair (C(s) symmetry), formed by the imino and amino tautomers of the adenine DNA base in the anti- and syn-conformations, respectively, bridging quantum-mechanical calculations with Bader's quantum theory of atoms in molecules. It was found that the A*·A(syn) ↔ A·A*(syn) tautomerisation is the asynchronous concerted process. It was established that the A*·A(syn) DNA mismatch is stabilized by the N6H···N6 (6.35) and N1H···N7 (6.17) hydrogen (H) bonds, whereas the A·A*(syn) base mispair (Cs) by the N6H···N6 (8.82) and N7H···N1 (9.78) H-bonds and the C8H···HC2 HH-bond (0.30 kcal mol(-1)). Using the sweeps of the energies of the intermolecular H-bonds, it was observed that the N6H···N6 and N1H···N7/N7H···N1 H-bonds are anti-cooperative and mutually weaken each other in the A*·A(syn) and A·A*(syn) mispairs. It was revealed that the A·A*(syn) DNA mismatch is a dynamically unstable structure with a short lifetime of 1.12 × 10(-13) s and any of its 6 low-frequency intermolecular vibrations can develop during this period of time. This observation makes it impossible to change the tautomeric status of the A bases upon the dissociation of the A*·A(syn) base mispair into the monomers during DNA replication.

  9. Use of the FLOTAC technique to diagnosing parasites of the urinary tract of dogs.

    PubMed

    Lima, Victor Fernando Santana; Ramos, Rafael Antonio Nascimento; Lepold, Raphael; Cringoli, Giuseppe; Rinaldi, Laura; Faustino, Maria Aparecida da Glória; Alves, Leucio Câmara

    2016-04-01

    Among the nematodes that infect the urinary tract of dogs, the Dioctophyma renale and Capillaria plica are those more frequently reported. For a long time, sedimentation was the only method used to detect eggs of these parasites in urine. The aim of this study was to analyze urine samples (n = 54) of dogs, obtained by bladder catheterization or cystocentesis, by using a modified FLOTAC technique. Animals were divided into two groups, i.e., with (n = 20) and without (n = 34) suspicion of urinary disease. The overall positivity herein observed was 3.8 % (2/54), being all animals (10 %; 2/20) from the group with suspicion of urinary disease. In the first positive sample, a single egg of D. renale was detected, whereas in the second sample two trematode-like eggs were observed. This is the first short survey employed to detect eggs of parasites that inhabit the urinary tract of dogs using a modified FLOTAC technique; in addition, for the first time, eggs of D. renale have been detected using this tool.

  10. syn-Selective crotylation of aldehydes using bismuth-crotyl bromide-(1-butyl-3-methylimidazolium bromide) combination: some synthetic applications.

    PubMed

    Goswami, Dibakar; Koli, Mrunesh R; Chatterjee, Sucheta; Chattopadhyay, Subrata; Sharma, Anubha

    2017-05-03

    The Bi-[bmim][Br] combination has been found to offer high syn-selectivity in the crotylation of aldehydes with crotyl bromide using practically stoichiometric amounts of the reagents. The room temperature ionic liquid (RTIL), [bmim][Br], activated Bi metal in the presence of oxygen to produce crotylbismuthdibromide, which reacted with the aldehydes at room temperature. The major anti-syn diastereomeric product obtained from the crotylation of (R)-cyclohexylideneglyceraldehyde was utilized for the synthesis of dictyostatin and cryptophycin segments, and (+)-cis-aerangis lactone, using standard synthetic protocols.

  11. SynBioSS designer: a web-based tool for the automated generation of kinetic models for synthetic biological constructs

    PubMed Central

    Weeding, Emma; Houle, Jason

    2010-01-01

    Modeling tools can play an important role in synthetic biology the same way modeling helps in other engineering disciplines: simulations can quickly probe mechanisms and provide a clear picture of how different components influence the behavior of the whole. We present a brief review of available tools and present SynBioSS Designer. The Synthetic Biology Software Suite (SynBioSS) is used for the generation, storing, retrieval and quantitative simulation of synthetic biological networks. SynBioSS consists of three distinct components: the Desktop Simulator, the Wiki, and the Designer. SynBioSS Designer takes as input molecular parts involved in gene expression and regulation (e.g. promoters, transcription factors, ribosome binding sites, etc.), and automatically generates complete networks of reactions that represent transcription, translation, regulation, induction and degradation of those parts. Effectively, Designer uses DNA sequences as input and generates networks of biomolecular reactions as output. In this paper we describe how Designer uses universal principles of molecular biology to generate models of any arbitrary synthetic biological system. These models are useful as they explain biological phenotypic complexity in mechanistic terms. In turn, such mechanistic explanations can assist in designing synthetic biological systems. We also discuss, giving practical guidance to users, how Designer interfaces with the Registry of Standard Biological Parts, the de facto compendium of parts used in synthetic biology applications. PMID:20639523

  12. Millimeter-wave spectroscopy of syn formyl azide (HC(O)N3) in seven vibrational states

    NASA Astrophysics Data System (ADS)

    Walters, Nicholas A.; Amberger, Brent K.; Esselman, Brian J.; Woods, R. Claude; McMahon, Robert J.

    2017-01-01

    Millimeter-wave spectra for formyl azide (HC(O)N3) were obtained from 240 to 360 GHz at ambient temperature. For the ground state of syn formyl azide, over 1500 independent rotational transitions were measured and least-squares fit to a complete S-reduced 8th order centrifugal distortion/rigid rotor Hamiltonian. The decomposition of formyl azide was monitored over a period of several hours, the half-life (t½ = 30 min) was determined, and its decomposition products were investigated. Transitions from five vibrational satellites of syn formyl azide (ν9, ν12, 2ν9, ν9 + ν12, and ν11) were observed, measured, and least-squares fit to complete or nearly complete octic centrifugally-distorted, single-state S-reduced models. A less complete single-state fit of 3ν9 (509.3 cm-1) was obtained from an unperturbed subset of its assignable transitions. This state is apparently coupled to the fundamental ν8 (489.4 cm-1) and the overtone 2ν12 (503.6 cm-1), but the coupling remains unanalyzed. Anharmonic CCSD(T)/ANO1 estimates of the vibrational frequencies of syn formyl azide were in close agreement with previously published experimental and computational values. Experimentally determined vibration-rotation interaction (αi) values were in excellent agreement with coupled-cluster predicted αi values for the fundamentals ν9, ν12, and ν11.

  13. The Southampton-York Natural Scenes (SYNS) dataset: Statistics of surface attitude

    PubMed Central

    Adams, Wendy J.; Elder, James H.; Graf, Erich W.; Leyland, Julian; Lugtigheid, Arthur J.; Muryy, Alexander

    2016-01-01

    Recovering 3D scenes from 2D images is an under-constrained task; optimal estimation depends upon knowledge of the underlying scene statistics. Here we introduce the Southampton-York Natural Scenes dataset (SYNS: https://syns.soton.ac.uk), which provides comprehensive scene statistics useful for understanding biological vision and for improving machine vision systems. In order to capture the diversity of environments that humans encounter, scenes were surveyed at random locations within 25 indoor and outdoor categories. Each survey includes (i) spherical LiDAR range data (ii) high-dynamic range spherical imagery and (iii) a panorama of stereo image pairs. We envisage many uses for the dataset and present one example: an analysis of surface attitude statistics, conditioned on scene category and viewing elevation. Surface normals were estimated using a novel adaptive scale selection algorithm. Across categories, surface attitude below the horizon is dominated by the ground plane (0° tilt). Near the horizon, probability density is elevated at 90°/270° tilt due to vertical surfaces (trees, walls). Above the horizon, probability density is elevated near 0° slant due to overhead structure such as ceilings and leaf canopies. These structural regularities represent potentially useful prior assumptions for human and machine observers, and may predict human biases in perceived surface attitude. PMID:27782103

  14. Syn-collisional felsic magmatism and continental crust growth: A case study from the North Qilian Orogenic Belt at the northern margin of the Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Chen, Shuo; Niu, Yaoling; Xue, Qiqi

    2018-05-01

    The abundant syn-collisional granitoids produced and preserved at the northern Tibetan Plateau margin provide a prime case for studying the felsic magmatism as well as continental crust growth in response to continental collision. Here we present the results from a systematic study of the syn-collisional granitoids and their mafic magmatic enclaves (MMEs) in the Laohushan (LHS) and Machangshan (MCS) plutons from the North Qilian Orogenic Belt (NQOB). Two types of MMEs from the LHS pluton exhibit identical crystallization age ( 430 Ma) and bulk-rock isotopic compositions to their host granitoids, indicating their genetic link. The phase equilibrium constraints and pressure estimates for amphiboles from the LHS pluton together with the whole rock data suggest that the two types of MMEs represent two evolution products of the same hydrous andesitic magmas. In combination with the data on NQOB syn-collisional granitoids elsewhere, we suggest that the syn-collisional granitoids in the NQOB are material evidence of melting of ocean crust and sediment. The remarkable compositional similarity between the LHS granitoids and the model bulk continental crust in terms of major elements, trace elements, and some key element ratios indicates that the syn-collisional magmatism in the NQOB contributes to net continental crust growth, and that the way of continental crust growth in the Phanerozoic through syn-collisional felsic magmatism (production and preservation) is a straightforward process without the need of petrologically and physically complex processes.

  15. A synthetic cadmium metallothionein gene (PMCd1syn) of Paramecium species: expression, purification and characteristics of metallothionein protein.

    PubMed

    Dar, Saira; Shuja, Rukhsana N; Shakoori, Abdul Rauf

    2013-02-01

    Metallothioneins (MTs) are metal binding proteins that are rich in cysteine residues constituting 10-30 % of the total protein, and in which the thiol groups bind to the metal ions. The increasing amount of metal ions in the medium have shown increased production of MTs by different organisms such as bacteria, protozoa and mammals like humans. PMCd1 is the first gene ever discovered in Paramecium, a ciliated protozoan, that could produce this MT in response to cadmium. In this study the PMCd1syn gene has been cloned in pET41a expression vector and expressed in an Escherichia coli BL21-codonplus strain for the first time. Since the gene PMCd1 amplified from Paramecium contained 10 codons, which could act as stop codons during expression in E. coli, this gene of 612 bps was synthesized to substitute these (stop) codons for the Paramecium sp. specific amino acids. For stability of the expressed protein, glutathione-S-transferase gene was fused with PMCd1syn gene and coexpressed. The cells expressing PMCd1syn demonstrated increased accumulation of cadmium. This is the first report of cadmium MT protein expressed from Paramecium species, particularly from synthetic MT gene (PMCd1syn). This fusion protein, the molecular weight of which has been confirmed to be 53.03 kDa with MALDI analysis, is rich in cysteine residues, and has been shown for the first time in this ciliate to bind to and sequester Cd(2+)-ions.

  16. Internal hysteresis experienced on a high pressure syn gas compressor

    NASA Technical Reports Server (NTRS)

    Zeidan, F. Y.

    1984-01-01

    A vibration instability phenomenon experienced in operating high pressure syn gas centrifugal compressors in two ammonia plants is described. The compressors were monitored by orbit and spectrum analysis for changes from baseline readings. It is found that internal hysteresis was the major destabilizing force; however, the problem was further complicated by seal lockup at the suction end of the compressor. A coupling lockup problem and a coupling fit problem, which frettage of the shaft, are also considered as contributors to the self excited vibrations.

  17. [Relationship between the Expression of α-syn and Neuronal Apoptosis in Brain Cortex of Acute Alcoholism Rats].

    PubMed

    Li, F; Zhang, Y; Ma, S L

    2016-12-01

    To observe the changes of expression of α-synuclein (α-syn) and neuronal apoptosis in brain cortex of acute alcoholism rats and to explore the mechanism of the damage caused by ethanol to the neurons. The model of acute alcoholism rat was established by 50% alcohol gavage. The α-syn and caspase-3 were detected by immunohistochemical staining and imaging analysis at 1 h, 3 h, 6 h and 12 h after acute alcoholism. The number of positive cell and mean of optical density were detected and the trend change was analyzed. The variance analysis and t -test were also performed. The number of α-syn positive cell and average optical density in brain cortex of acute alcoholism rat increased significantly and peaked at 6 hour with a following slight decrease at 12 h, but still higher than the groups at 1 h and 3 h. Within 12 hours after poisoning, the number of caspase-3 positive cell and average optical density in brain cortex of rats gradually increased. The abnormal aggregation of α-syn caused by brain edema and hypoxia may participate the early stage of neuronal apoptosis in brain cortex after acute alcoholism. Copyright© by the Editorial Department of Journal of Forensic Medicine

  18. Configurational and conformational preferences in oximes and oxime carbanions. Ab initio study of the syn effect in reactions of oxyimine enolate equivalents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Glaser, R.; Streitwieser, A.

    1989-09-13

    Geometries and relative energies of stationary structures of several conformers of geometrical isomers of NO s-trans-configured acetaldoxime are reported. The calculated energies and geometries agree well with comparable experimental data. Effects of the theoretical model on the NO band lengths are discussed for formaldoxime. The theoretical results suggest that the regiochemistry of enolate equivalents of oxyimines in dissociating solvents is due to the thermodynamic syn preference of the anions. Syn/anti isomerization of the anions (E{sub a} < 26 kcal mol{sup {minus}1}) is rapid even at low temperatures. In contrast, the anti preference of the radicals of acetaldoxime indicates that themore » formation of the syn products in oxidative coupling reactions of the anions of oxime ethers is a kinetic effect.« less

  19. Retrieving SW fluxes from geostationary narrowband radiances for the NASA-CERES SYN1deg product

    NASA Astrophysics Data System (ADS)

    Wrenn, F. J., IV; Doelling, D. R.; Liang, L.

    2016-12-01

    The CERES mission was designed to measure the natural variability of the net TOA flux over long time scales relevant to climate monitoring. To achieve this goal, CERES provides the level-3 SSF1deg, SYN1deg, and EBAF monthly 1° by 1° regional TOA flux. The single satellite (Terra or Aqua) SSF1deg 24-hour shortwave flux is based on one daytime measurements and assumes constant meteorology to model the diurnal change in albedo. To accurately describe regions with a prominent diurnal signal, the SYN1deg Edition4 dataset employs hourly geostationary (GEO) measurements. This improves upon Edition3, which used 3-hourly GEO measurements and with temporal interpolation. The EBAF product combines the temporal stability of the SSF1deg product with the diurnal information from SYN1deg and removes the CERES instrument calibration bias by constraining the net flux balance to the ocean heat storage term. The SYN-1deg product retrieves hourly SW fluxes from GEO measurements. Over regions with large diurnal cycles, such as maritime stratus and land afternoon convective locations, the GEO derived SW fluxes will capture the diurnal flux not observed with Terra or Aqua sun-synchronous satellites. Obtaining fluxes from geostationary satellite radiance is a multistep process. First, most GEO visible imagers lack calibration and must be calibrated to MODIS and VIIRS. Second, the GEO imager visible channel radiances are converted to broadband radiances using empirical and theoretical models. The lack of coincident, collocated, and co-angled GEO and CERES measurements makes building an empirical model difficult. The narrowband to broadband models are a function of surface and cloud conditions, which are difficult to identify due to the inconsistent cloud retrievals between the 16 GEO imagers used in the CERES record. Third, the GEO derived broadband radiances are passed through the CERES angular distribution model (ADM) to convert the radiances to fluxes. Lastly, the GEO derived

  20. Retrieving SW fluxes from geostationary narrowband radiances for the NASA-CERES SYN1deg product

    NASA Astrophysics Data System (ADS)

    Wrenn, F. J., IV; Doelling, D. R.; Liang, L.

    2017-12-01

    The CERES mission was designed to measure the natural variability of the net TOA flux over long time scales relevant to climate monitoring. To achieve this goal, CERES provides the level-3 SSF1deg, SYN1deg, and EBAF monthly 1° by 1° regional TOA flux. The single satellite (Terra or Aqua) SSF1deg 24-hour shortwave flux is based on one daytime measurements and assumes constant meteorology to model the diurnal change in albedo. To accurately describe regions with a prominent diurnal signal, the SYN1deg Edition4 dataset employs hourly geostationary (GEO) measurements. This improves upon Edition3, which used 3-hourly GEO measurements and with temporal interpolation. The EBAF product combines the temporal stability of the SSF1deg product with the diurnal information from SYN1deg and removes the CERES instrument calibration bias by constraining the net flux balance to the ocean heat storage term. The SYN-1deg product retrieves hourly SW fluxes from GEO measurements. Over regions with large diurnal cycles, such as maritime stratus and land afternoon convective locations, the GEO derived SW fluxes will capture the diurnal flux not observed with Terra or Aqua sun-synchronous satellites. Obtaining fluxes from geostationary satellite radiance is a multistep process. First, most GEO visible imagers lack calibration and must be calibrated to MODIS and VIIRS. Second, the GEO imager visible channel radiances are converted to broadband radiances using empirical and theoretical models. The lack of coincident, collocated, and co-angled GEO and CERES measurements makes building an empirical model difficult. The narrowband to broadband models are a function of surface and cloud conditions, which are difficult to identify due to the inconsistent cloud retrievals between the 16 GEO imagers used in the CERES record. Third, the GEO derived broadband radiances are passed through the CERES angular distribution model (ADM) to convert the radiances to fluxes. Lastly, the GEO derived

  1. Effect of Hawthorn (Crataegus aronia syn. Azarolus (L)) on platelet function in albino Wistar rats.

    PubMed

    Shatoor, Abdullah S; Soliman, Hesham; Al-Hashem, Fahaid; Gamal, Basiouny El-; Othman, Adel; El-Menshawy, Nadia

    2012-07-01

    This study was designed to investigate the possible antiplatelet effect of aqueous whole-plant C. aronia syn: Azarolus (L) extract using Wistar albino rats as a model. Forty-two male albino Wistar rats weighing 200 to 250 g were divided into seven groups with six rats in each group. Group 1 served as the control and received equal volumes of distilled water. Groups 2-6 served as the experimental groups and were given C. aronia extract at doses of 100, 200, 500, 1,000, and 2,000 mg/kg, while group 7 served as a positive control and was given aspirin (25mg/kg). All the doses were administered orally once a day and the treatment was continued for seven days. In all groups, at the end of the experimental procedure, blood samples were obtained for platelet function measurements, including PFA-100, thromboxane B2 levels, platelet count, and haematocrit. The bleeding time was determined using a modified tail cutting method described previously. The aqueous C. aronia syn. Azarolus (L) extract significantly altered the bleeding time and the closure time, as determined by the PFA-100 and thromboxane B2 levels, suggesting significant platelet function inhibition. These effects were observed with C. aronia doses between 100 - 500 mg/kg, which yielded thromboxane B2 levels of 1,000 mg/kg, whereas the higher dose (2,000 mg/kg) produced opposite effects on these parameters. C. aronia syn. Azarolus (L) aqueous extract has antiplatelet effects in Wistar albino rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. In vivo hemodynamic and electrocardiographic changes following Crataegus aronia syn. Azarolus L administration to normotensive Wistar rats.

    PubMed

    Shatoor, Abdullah S

    2013-02-01

    To evaluate the effects of the whole plant aqueous extract of Crataegus aronia (C. aronia) syn. Azarolus (L) on the hemodynamic and electrocardiographic intervals in albino rats. This study was carried out in 2 stages at the Research Laboratory, Physiology Department, Medical College of King Khalid University, Abha, Kingdom of Saudi Arabia between February and June 2012. First, the effects of C. aronia syn. Azarolus (L) on the hemodynamics and electrocardiograph in 54 Wistar male rats were assessed, then the mechanisms underlying the hemodynamic and electrocardiographic changes observed in the first stage were evaluated in 48 rats of the same species. The C. aronia administered at escalating doses (0.05-20 microgram/kg) produced a dose-time-dependent decrease in heart rate (HR) and mean arterial pressure (MAP). Higher doses (15 and 20 microgram/kg) produced the most significant reduction in both HR and MAP, and induced sinus node suppression and progressive atrio-ventricular blockade. The underlying mechanism of the induced bradyarrhythmia appeared to be due to the direct stimulation of the muscarinic receptor M2 and possible blockade of beta-receptors, while the hypotension was caused by enhanced nitric oxide release. No significant alterations in the electrocardiogram (ECG) components were observed. The administration of the C. aronia syn. Azarolus extract induced bradyarrhythmia and hypotension, without alteration in the ECG components.

  3. Canine and feline cardiopulmonary parasitic nematodes in Europe: emerging and underestimated

    PubMed Central

    2010-01-01

    Cardiopulmonary nematodes of dogs and cats cause parasitic diseases of central relevance in current veterinary practice. In the recent past the distribution of canine and feline heartworms and lungworms has increased in various geographical areas, including Europe. This is true especially for the metastrongyloids Aelurostrongylus abstrusus, Angiostrongylus vasorum and Crenosoma vulpis, the filarioid Dirofilaria immitis and the trichuroid Eucoleus aerophilus (syn. Capillaria aerophila). The reasons of this emergence are little known but many drivers such as global warming, changes in vector epidemiology and movements in animal populations, may be taken into account. The purpose of this article is to review the knowledge of the most important heartworm and lungworm infections of dogs and cats in Europe. In particular recent advances in epidemiology, clinical and control are described and discussed. PMID:20653938

  4. Synthesis of syn-4,6-dimethyldodecanal, the male sex pheromone and trail-following pheromone of two species of the termite Zootermopsis.

    PubMed

    Ghostin, J; Bordereau, C; Braekman, J C

    2011-03-01

    Recently, we reported that syn-4,6-dimethyldodecanal is the male sex pheromone and the trail-following pheromone of the Termopsidae Zootermopsis nevadensis and Zootermopsis angusticollis. In this article, we describe the syntheses of the mixture of the four stereoisomers of 4,6-dimethyldodecanal using a synthetic pathway where the key step is a Wittig reaction between methyl 4-methyl-5-oxo-pentanoate and 1-methylheptyl-triphenylphosphonium iodide, and of (±)-syn-4,6-dimethyldodecanal starting from 3,5-dimethyl-2-cyclohexen-1-one. Direct GC-MS comparison of these synthetic samples with the natural pheromone allowed its unambiguous identification.

  5. Phosphorylation of Synaptic GTPase-activating Protein (synGAP) by Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII) and Cyclin-dependent Kinase 5 (CDK5) Alters the Ratio of Its GAP Activity toward Ras and Rap GTPases*

    PubMed Central

    Walkup, Ward G.; Washburn, Lorraine; Sweredoski, Michael J.; Carlisle, Holly J.; Graham, Robert L.; Hess, Sonja; Kennedy, Mary B.

    2015-01-01

    synGAP is a neuron-specific Ras and Rap GTPase-activating protein (GAP) found in high concentrations in the postsynaptic density (PSD) fraction from the mammalian forebrain. We have previously shown that, in situ in the PSD fraction or in recombinant form in Sf9 cell membranes, synGAP is phosphorylated by Ca2+/calmodulin-dependent protein kinase II (CaMKII), another prominent component of the PSD. Here, we show that recombinant synGAP (r-synGAP), lacking 102 residues at the N terminus, can be purified in soluble form and is phosphorylated by cyclin-dependent kinase 5 (CDK5) as well as by CaMKII. Phosphorylation of r-synGAP by CaMKII increases its HRas GAP activity by 25% and its Rap1 GAP activity by 76%. Conversely, phosphorylation by CDK5 increases r-synGAP's HRas GAP activity by 98% and its Rap1 GAP activity by 20%. Thus, phosphorylation by both kinases increases synGAP activity; CaMKII shifts the relative GAP activity toward inactivation of Rap1, and CDK5 shifts the relative activity toward inactivation of HRas. GAP activity toward Rap2 is not altered by phosphorylation by either kinase. CDK5 phosphorylates synGAP primarily at two sites, Ser-773 and Ser-802. Phosphorylation at Ser-773 inhibits r-synGAP activity, and phosphorylation at Ser-802 increases it. However, the net effect of concurrent phosphorylation of both sites, Ser-773 and Ser-802, is an increase in GAP activity. synGAP is phosphorylated at Ser-773 and Ser-802 in the PSD fraction, and its phosphorylation by CDK5 and CaMKII is differentially regulated by activation of NMDA-type glutamate receptors in cultured neurons. PMID:25533468

  6. A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density

    PubMed Central

    Walkup, Ward G; Mastro, Tara L; Schenker, Leslie T; Vielmetter, Jost; Hu, Rebecca; Iancu, Ariella; Reghunathan, Meera; Bannon, Barry Dylan; Kennedy, Mary B

    2016-01-01

    SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold, which would free PDZ domains for occupancy by other proteins. Finally, we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP. DOI: http://dx.doi.org/10.7554/eLife.16813.001 PMID:27623146

  7. Inversion of Configuration at the Phosphorus Nucleophile in the Diastereoselective and Enantioselective Synthesis of P-Stereogenic syn-Phosphiranes from Chiral Epoxides.

    PubMed

    Muldoon, Jake A; Varga, Balázs R; Deegan, Meaghan M; Chapp, Timothy W; Eördögh, Ádám M; Hughes, Russell P; Glueck, David S; Moore, Curtis E; Rheingold, Arnold L

    2018-04-23

    Nucleophilic substitution results in inversion of configuration at the electrophilic carbon center (S N 2) or racemization (S N 1). The stereochemistry of the nucleophile is rarely considered, but phosphines, which have a high barrier to pyramidal inversion, attack electrophiles with retention of configuration at P. Surprisingly, cyclization of bifunctional secondary phosphine alkyl tosylates proceeded under mild conditions with inversion of configuration at the nucleophile to yield P-stereogenic syn-phosphiranes. DFT studies suggested that the novel stereochemistry results from acid-promoted tosylate dissociation to yield an intermediate phosphenium-bridged cation, which undergoes syn-selective cyclization. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Purine 3':5'-cyclic nucleotides with the nucleobase in a syn orientation: cAMP, cGMP and cIMP.

    PubMed

    Řlepokura, Katarzyna Anna

    2016-06-01

    Purine 3':5'-cyclic nucleotides are very well known for their role as the secondary messengers in hormone action and cellular signal transduction. Nonetheless, their solid-state conformational details still require investigation. Five crystals containing purine 3':5'-cyclic nucleotides have been obtained and structurally characterized, namely adenosine 3':5'-cyclic phosphate dihydrate, C10H12N5O6P·2H2O or cAMP·2H2O, (I), adenosine 3':5'-cyclic phosphate 0.3-hydrate, C10H12N5O6P·0.3H2O or cAMP·0.3H2O, (II), guanosine 3':5'-cyclic phosphate pentahydrate, C10H12N5O7P·5H2O or cGMP·5H2O, (III), sodium guanosine 3':5'-cyclic phosphate tetrahydrate, Na(+)·C10H11N5O7P(-)·4H2O or Na(cGMP)·4H2O, (IV), and sodium inosine 3':5'-cyclic phosphate tetrahydrate, Na(+)·C10H10N4O7P(-)·4H2O or Na(cIMP)·4H2O, (V). Most of the cyclic nucleotide zwitterions/anions [two from four cAMP present in total in (I) and (II), cGMP in (III), cGMP(-) in (IV) and cIMP(-) in (V)] are syn conformers about the N-glycosidic bond, and this nucleobase arrangement is accompanied by Crib-H...Npur hydrogen bonds (rib = ribose and pur = purine). The base orientation is tuned by the ribose pucker. An analysis of data obtained from the Cambridge Structural Database made in the context of syn-anti conformational preferences has revealed that among the syn conformers of various purine nucleotides, cyclic nucleotides and dinucleotides predominate significantly. The interactions stabilizing the syn conformation have been indicated. The inter-nucleotide contacts in (I)-(V) have been systematized in terms of the chemical groups involved. All five structures display three-dimensional hydrogen-bonded networks.

  9. Geometry and architecture of faults in a syn-rift normal fault array: The Nukhul half-graben, Suez rift, Egypt

    NASA Astrophysics Data System (ADS)

    Wilson, Paul; Gawthorpe, Rob L.; Hodgetts, David; Rarity, Franklin; Sharp, Ian R.

    2009-08-01

    The geometry and architecture of a well exposed syn-rift normal fault array in the Suez rift is examined. At pre-rift level, the Nukhul fault consists of a single zone of intense deformation up to 10 m wide, with a significant monocline in the hanging wall and much more limited folding in the footwall. At syn-rift level, the fault zone is characterised by a single discrete fault zone less than 2 m wide, with damage zone faults up to approximately 200 m into the hanging wall, and with no significant monocline developed. The evolution of the fault from a buried structure with associated fault-propagation folding, to a surface-breaking structure with associated surface faulting, has led to enhanced bedding-parallel slip at lower levels that is absent at higher levels. Strain is enhanced at breached relay ramps and bends inherited from pre-existing structures that were reactivated during rifting. Damage zone faults observed within the pre-rift show ramp-flat geometries associated with contrast in competency of the layers cut and commonly contain zones of scaly shale or clay smear. Damage zone faults within the syn-rift are commonly very straight, and may be discrete fault planes with no visible fault rock at the scale of observation, or contain relatively thin and simple zones of scaly shale or gouge. The geometric and architectural evolution of the fault array is interpreted to be the result of (i) the evolution from distributed trishear deformation during upward propagation of buried fault tips to surface faulting after faults breach the surface; (ii) differences in deformation response between lithified pre-rift units that display high competence contrasts during deformation, and unlithified syn-rift units that display low competence contrasts during deformation, and; (iii) the history of segmentation, growth and linkage of the faults that make up the fault array. This has important implications for fluid flow in fault zones.

  10. Chemical communication in termites: syn-4,6-dimethylundecan-1-ol as trail-following pheromone, syn-4,6-dimethylundecanal and (5E)-2,6,10-trimethylundeca-5,9-dienal as the respective male and female sex pheromones in Hodotermopsis sjoestedti (Isoptera, Archotermopsidae).

    PubMed

    Lacey, Michael J; Sémon, Etienne; Krasulová, Jana; Sillam-Dussès, David; Robert, Alain; Cornette, Richard; Hoskovec, Michal; Záček, Petr; Valterová, Irena; Bordereau, Christian

    2011-12-01

    The trail-following pheromone and sex pheromones were investigated in the Indomalayan termite Hodotermopsis sjoestedti belonging to the new family Archotermopsidae. Gas chromatography coupled to mass spectrometry (GC-MS) after solid phase microextraction (SPME) of the sternal gland secretion of pseudergates and trail-following bioassays demonstrated that the trail-following pheromone of H. sjoestedti was syn-4,6-dimethylundecan-1-ol, a new chemical structure for termite pheromones. GC-MS after SPME of the sternal gland secretion of alates also allowed the identification of sex-specific compounds. In female alates, the major sex-specific compound was identified as (5E)-2,6,10-trimethylundeca-5,9-dienal, a compound previously identified as the female sex pheromone of the termite Zootermopsis nevadensis. In male alates, the major sex-specific compound was identified as syn-4,6-dimethylundecanal, a homolog of syn-4,6-dimethyldodecanal, which has previously been confirmed as the male sex pheromone of Z. nevadensis. The presence of sex-specific compounds in alates of H. sjoestedti strongly suggests for this termite the presence of sex-specific pairing pheromones which were only known until now in Z. nevadensis. Our results showed therefore a close chemical relationship between the pheromones of the taxa Hodotermopsis and Zootermopsis and, in contrast, a clear difference with the taxa Stolotermes and Porotermes, which is in total agreement with the recent creation of the families Archotermopsidae and Stolotermitidae as a substitute for the former family Termopsidae. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Heterobimetallic transition metal/rare earth metal bifunctional catalysis: a Cu/Sm/Schiff base complex for syn-selective catalytic asymmetric nitro-Mannich reaction.

    PubMed

    Handa, Shinya; Gnanadesikan, Vijay; Matsunaga, Shigeki; Shibasaki, Masakatsu

    2010-04-07

    The full details of a catalytic asymmetric syn-selective nitro-Mannich reaction promoted by heterobimetallic Cu/Sm/dinucleating Schiff base complexes are described, demonstrating the effectiveness of the heterobimetallic transition metal/rare earth metal bifunctional catalysis. The first-generation system prepared from Cu(OAc)(2)/Sm(O-iPr)(3)/Schiff base 1a = 1:1:1 with an achiral phenol additive was partially successful for achieving the syn-selective catalytic asymmetric nitro-Mannich reaction. The substrate scope and limitations of the first-generation system remained problematic. After mechanistic studies on the catalyst prepared from Sm(O-iPr)(3), we reoptimized the catalyst preparation method, and a catalyst derived from Sm(5)O(O-iPr)(13) showed broader substrate generality as well as higher reactivity and stereoselectivity compared to Sm(O-iPr)(3). The optimal system with Sm(5)O(O-iPr)(13) was applicable to various aromatic, heteroaromatic, and isomerizable aliphatic N-Boc imines, giving products in 66-99% ee and syn/anti = >20:1-13:1. Catalytic asymmetric synthesis of nemonapride is also demonstrated using the catalyst derived from Sm(5)O(O-iPr)(13).

  12. Development of an exposure measurement database on five lung carcinogens (ExpoSYN) for quantitative retrospective occupational exposure assessment.

    PubMed

    Peters, Susan; Vermeulen, Roel; Olsson, Ann; Van Gelder, Rainer; Kendzia, Benjamin; Vincent, Raymond; Savary, Barbara; Williams, Nick; Woldbæk, Torill; Lavoué, Jérôme; Cavallo, Domenico; Cattaneo, Andrea; Mirabelli, Dario; Plato, Nils; Dahmann, Dirk; Fevotte, Joelle; Pesch, Beate; Brüning, Thomas; Straif, Kurt; Kromhout, Hans

    2012-01-01

    SYNERGY is a large pooled analysis of case-control studies on the joint effects of occupational carcinogens and smoking in the development of lung cancer. A quantitative job-exposure matrix (JEM) will be developed to assign exposures to five major lung carcinogens [asbestos, chromium, nickel, polycyclic aromatic hydrocarbons (PAH), and respirable crystalline silica (RCS)]. We assembled an exposure database, called ExpoSYN, to enable such a quantitative exposure assessment. Existing exposure databases were identified and European and Canadian research institutes were approached to identify pertinent exposure measurement data. Results of individual air measurements were entered anonymized according to a standardized protocol. The ExpoSYN database currently includes 356 551 measurements from 19 countries. In total, 140 666 personal and 215 885 stationary data points were available. Measurements were distributed over the five agents as follows: RCS (42%), asbestos (20%), chromium (16%), nickel (15%), and PAH (7%). The measurement data cover the time period from 1951 to present. However, only a small portion of measurements (1.4%) were performed prior to 1975. The major contributing countries for personal measurements were Germany (32%), UK (22%), France (14%), and Norway and Canada (both 11%). ExpoSYN is a unique occupational exposure database with measurements from 18 European countries and Canada covering a time period of >50 years. This database will be used to develop a country-, job-, and time period-specific quantitative JEM. This JEM will enable data-driven quantitative exposure assessment in a multinational pooled analysis of community-based lung cancer case-control studies.

  13. A double chain reversal loop and two diagonal loops define the architecture of a unimolecular DNA quadruplex containing a pair of stacked G(syn)-G(syn)-G(anti)-G(anti) tetrads flanked by a G-(T-T) Triad and a T-T-T triple.

    PubMed

    Kuryavyi, V; Majumdar, A; Shallop, A; Chernichenko, N; Skripkin, E; Jones, R; Patel, D J

    2001-06-29

    The architecture of G-G-G-G tetrad-aligned DNA quadruplexes in monovalent cation solution is dependent on the directionality of the four strands, which in turn are defined by loop connectivities and the guanine syn/anti distribution along individual strands and within individual G-G-G-G tetrads. The smallest unimolecular G-quadruplex belongs to the d(G2NnG2NnG2NnG2) family, which has the potential to form two stacked G-tetrads linked by Nn loop connectivities. Previous studies have focused on the thrombin-binding DNA aptamer d(G2T2G2TGTG2T2G2), where Nn was T2 for the first and third connecting loops and TGT for the middle connecting loop. This DNA aptamer in K(+) cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)-G(anti)-G(syn)-G(anti) tetrads, adjacent strands which are antiparallel to each other and edge-wise connecting T2, TGT and T2 loops. We now report on the NMR-based solution structure of the d(G2T4G2CAG2GT4G2T) sequence, which differs from the thrombin-binding DNA aptamer sequence in having longer first (T4) and third (GT4) loops and a shorter (CA) middle loop. This d(G2T4G2CAG2GT4G2T) sequence in Na(+) cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)-G(syn)-G(anti)-G(anti) tetrads, adjacent strands which have one parallel and one antiparallel neighbors and distinct non-edge-wise loop connectivities. Specifically, the longer first (T4) and third (GT4) loops are of the diagonal type while the shorter middle loop is of the double chain reversal type. In addition, the pair of stacked G-G-G-G tetrads are flanked on one side by a G-(T-T) triad and on the other side by a T-T-T triple. The distinct differences in strand directionalities, loop connectivities and syn/anti distribution within G-G-G-G tetrads between the thrombin-binding DNA aptamer d(G2T2G2TGTG2T2G2) quadruplex reported previously, and the d(G2T4G2CAG2GT4G2T) quadruplex reported here, reinforces the polymorphic nature of higher

  14. Syn-deformational features of Carlin-type Au deposits

    USGS Publications Warehouse

    Peters, S.G.

    2004-01-01

    Syn-deformational ore deposition played an important role in some Carlin-type Au deposits according to field and laboratory evidence, which indicates that flow of Au-bearing fluids was synchronous with regional-scale deformation events. Gold-related deformation events linked to ore genesis were distinct from high-level, brittle deformation that is typical of many epithermal deposits. Carlin-type Au deposits, with brittle-ductile features, most likely formed during tectonic events that were accompanied by significant fluid flow. Interactive deformation-fluid processes involved brittle-ductile folding, faulting, shearing, and gouge development that were focused along illite-clay and dissolution zones caused by hydrothermal alteration. Alteration along these deformation zones resulted in increased porosity and enhancement of fluid flow, which resulted in decarbonated, significant dissolution, collapse, and volume and mass reduction. Carlin-type Au deposits commonly are hosted in Paleozoic and Mesozoic sedimentary rocks (limestone, siltstone, argillite, shale, and quartzite) on the margins of cratons. The sedimentary basins containing the host rocks underwent tectonic events that influenced the development of stratabound, structurally controlled orebodies. Published by Elsevier Ltd.

  15. A first step beyond traditional boundaries: destination therapy with the SynCardia total artificial heart.

    PubMed

    Spiliopoulos, Sotirios; Koerfer, Reiner; Tenderich, Gero

    2014-06-01

    The SynCardia total artificial heart is currently used as a bridge to transplantation therapy in cases of irreversible, acute or chronic, biventricular heart failure. We describe the implementation of this technology in the context of destination therapy in a patient with an end-stage heart failure on grounds of primary amyloidosis. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  16. A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo.

    PubMed

    Das, Banibrata; Rajagopalan, Subramanian; Joshi, Gnanada S; Xu, Liping; Luo, Dan; Andersen, Julie K; Todi, Sokol V; Dutta, Aloke K

    2017-09-01

    Here, we report the characterization of a novel hybrid D 2 /D 3 agonist and iron (II) specific chelator, D-607, as a multi-target-directed ligand against Parkinson's disease (PD). In our previously published report, we showed that D-607 is a potent agonist of dopamine (DA) D 2 /D 3 receptors, exhibits efficacy in a reserpinized PD animal model and preferentially chelates to iron (II). As further evidence of its potential as a neuroprotective agent in PD, the present study reveals D-607 to be protective in neuronal PC12 cells against 6-OHDA toxicity. In an in vivo Drosophila melanogaster model expressing a disease-causing variant of α-synuclein (α-Syn) protein in fly eyes, the compound was found to significantly suppress toxicity compared to controls, concomitant with reduced levels of aggregated α-Syn. Furthermore, D-607 was able to rescue DAergic neurons from MPTP toxicity in mice, a well-known PD neurotoxicity model, following both sub-chronic and chronic MPTP administration. Mechanistic studies indicated that possible protection of mitochondria, up-regulation of hypoxia-inducible factor, reduction in formation of α-Syn aggregates and antioxidant activity may underlie the observed neuroprotection effects. These observations strongly suggest that D-607 has potential as a promising multifunctional lead molecule for viable symptomatic and disease-modifying therapy for PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Acquiring research-grade ERPs on a shoestring budget: A comparison of a modified Emotiv and commercial SynAmps EEG system.

    PubMed

    Barham, Michael P; Clark, Gillian M; Hayden, Melissa J; Enticott, Peter G; Conduit, Russell; Lum, Jarrad A G

    2017-09-01

    This study compared the performance of a low-cost wireless EEG system to a research-grade EEG system on an auditory oddball task designed to elicit N200 and P300 ERP components. Participants were 15 healthy adults (6 female) aged between 19 and 40 (M = 28.56; SD = 6.38). An auditory oddball task was presented comprising 1,200 presentations of a standard tone interspersed by 300 trials comprising a deviant tone. EEG was simultaneously recorded from a modified Emotiv EPOC and a NeuroScan SynAmps RT EEG system. The modifications made to the Emotiv system included attaching research grade electrodes to the Bluetooth transmitter. Additional modifications enabled the Emotiv system to connect to a portable impedance meter. The cost of these modifications and portable impedance meter approached the purchase value of the Emotiv system. Preliminary analyses revealed significantly more trials were rejected from data acquired by the modified Emotiv compared to the SynAmps system. However, the ERP waveforms captured by the Emotiv system were found to be highly similar to the corresponding waveform from the SynAmps system. The latency and peak amplitude of N200 and P300 components were also found to be similar between systems. Overall, the results indicate that, in the context of an oddball task, the ERP acquired by a low-cost wireless EEG system can be of comparable quality to research-grade EEG acquisition equipment. © 2017 Society for Psychophysiological Research.

  18. Syn-anti conformational switching in an ethane-bridged Co(II)bisporphyrin induced by external stimuli: effects of inter-macrocyclic interactions, axial ligation and chemical and electrochemical oxidations.

    PubMed

    Dey, Soumyajit; Rath, Sankar Prasad

    2014-02-07

    The syn-anti conformational switching has been demonstrated in the ethane-bridged dicobalt(II)bisporphyrin which is present in the syn-form only. The addition of either perylene or axial ligands to Co(II)(bisporphyrin) completely transforms the syn form into the anti because of strong π-π interaction and axial coordination, respectively. The complex undergoes four 1e-oxidations in CH2Cl2 which are indicative of strong through space interactions between the two cofacial Co-porphyrins at 295 K. The first oxidation is a metal centered one and occurs at a potential much lower than that of the monomeric analog. However, the second oxidation, which is again metal centered, was at a significantly higher potential. The large difference between the first two oxidations, as observed here, is due to much stronger inter-porphyrin interactions. The step-wise oxidations have been performed both chemically and electro-chemically while the progress of the reactions was monitored by UV-visible and (1)H NMR spectroscopy. After 1e-oxidation, a very broad (1)H NMR signal results with increased difference between two meso resonances, which indicates that the two macrocycles are in the syn-form with lesser interplanar separation as also observed by DFT. However, 2e-oxidation results in the stabilization of the anti form. The addition of axial ligands to Co(II)(bisporphyrin) also completely transforms the syn form into the anti form. While additions of THF and I2/I(-) both result in the formation of five-coordinate complexes, Co(II) is oxidized to Co(III) in the case of the latter. However, additions of 1-methylimidazole, pyridine and pyrazine as axial ligands result in the formation of a six-coordinate complex in which Co(II) is spontaneously oxidized to Co(III) in air.

  19. Assessment of pre-crisis and syn-crisis seismic hazard at Campi Flegrei and Mt. Vesuvius volcanoes, Campania, southern Italy

    NASA Astrophysics Data System (ADS)

    Convertito, Vincenzo; Zollo, Aldo

    2011-08-01

    In this study, we address the issue of short-term to medium-term probabilistic seismic hazard analysis for two volcanic areas, Campi Flegrei caldera and Mt. Vesuvius in the Campania region of southern Italy. Two different phases of the volcanic activity are considered. The first, which we term the pre-crisis phase, concerns the present quiescent state of the volcanoes that is characterized by low-to-moderate seismicity. The second phase, syn-crisis, concerns the unrest phase that can potentially lead to eruption. For the Campi Flegrei case study, we analyzed the pattern of seismicity during the 1982-1984 ground uplift episode (bradyseism). For Mt. Vesuvius, two different time-evolutionary models for seismicity were adopted, corresponding to different ways in which the volcano might erupt. We performed a site-specific analysis, linked with the hazard map, to investigate the effects of input parameters, in terms of source geometry, mean activity rate, periods of data collection, and return periods, for the syn-crisis phase. The analysis in the present study of the pre-crisis phase allowed a comparison of the results of probabilistic seismic hazard analysis for the two study areas with those provided in the Italian national hazard map. For the Mt. Vesuvius area in particular, the results show that the hazard can be greater than that reported in the national hazard map when information at a local scale is used. For the syn-crisis phase, the main result is that the data recorded during the early months of the unrest phase are substantially representative of the seismic hazard during the whole duration of the crisis.

  20. Implantation technique of the 50-cm3 SynCardia Total Artificial Heart: does size make a difference?

    PubMed

    Spiliopoulos, Sotirios; Guersoy, Dilek; Dimitriou, Alexandros Merkourios; Koerfer, Reiner; Tenderich, Gero

    2015-01-01

    Despite downsizing, implantation technique of the 50-cm(3) SynCardia Total Artificial Heart and settings of the Companion driver remain unchanged. Owing to the absence of de-airing nipples, de-airing procedure is even more crucial and has to be performed carefully. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  1. Structural Transformation in the Northern Continental Margin of the South China Sea During Syn- and Post-Spreading Stages: Based on Study of Baiyun Sag in Pearl River Mouth Basin

    NASA Astrophysics Data System (ADS)

    Deng, P.; Mei, L.; Liu, J.; Liu, M.

    2016-12-01

    During the post-rift period, the northern continental margin of the South China Sea experienced syn-spreading stage related to the seafloor spreading from 32-15.5 Ma and post-spreading stage from 15.5-0 Ma. To recognize the structural difference and transformation between the syn- and post-spreading stags, we based on the interpretation of the high quality of 3D seismic data and comprehensively analyze the geometry and kinematics of faults, volcanism, magmatic diapirs and fluid actions of post-rift in Baiyun sag. The analysis reveals the syn-spreading stage can be divided into three episodes, namely Nanhai Episode One (32-29Ma), Nanhai Episode Two (24.4-21Ma) and Nanhai Episode Three (18.5-16.5Ma). Each of the three episodes has different geodynamic background: the first one is response to weak extensional structural environment at the beginning of the seafloor spreading, the second one is response to northward migration of the shelf slope-break in Baiyun sag, and the third one is response to strong subsidence of the Main Baiyun sag. During the syn-spreading stage, amount of effusive magma and polygonal faults developed, and the dynamics of the seafloor spreading shows migratory direction from south to north. The Post-spreading stage, which is response to the subduction compression from the Philippine plate in the east, can be divided into two episodes: Dongsha Episode One (12.5-10.5Ma) and Dongsha Episode Two (5.33-3.6Ma). During the post-spreading stage, each of episode has similar structural property and shows dynamic migration direction from east to west, besides there are much strong tectonism which are different from that of the syn-spreading stage's, such as magmatic diapirs and gas chimney. The structure has obvious transformation from syn- to post-spreading stage in Baiyun sag: faults plane pattern's transformation from dispersive and weak belt-like to X-shaped conjugated shear zone; tectonic evolution migration's transformation from northward migration to

  2. Westward-directed Grenvillian thrusting on the western margin of Fennoscandia: evidence from syn-kinematic pegmatites.

    NASA Astrophysics Data System (ADS)

    Henderson, I.

    2004-12-01

    Magmatism is often described as being syn-kinematic where one or more increments of intrusion punctuate deformation with successive generations of injections being progressively deformed. Recent studies have also demonstrated that there is a strong link between sites of concentrated magmatism and crustal deformation zones. Pegmatite formation in the Mesoproterozoic of south Norway has always been considered as post-kinematic in nature relative to Sveconorwegian (Grenvillian) deformation (1.13Ga to ~0.85Ga) during accretion of the SW margin of Baltica. We present structural data demonstrating that the pegmatites are kinematically related to fold geometries associated with peak metamorphism and form an integral part of the deformation episode associated with terrane accretion. Undeformed pegmatites are emplaced in sub-horizontal fractures suggesting that the maximum compressive stress was sub-horizontal. The pegmatites display a systematic deformation pattern that is consistent with deformation in the limbs of the isoclinal folds in the country rock into which they intrude. The sense of shear of deformation kinematics on the pegmatites reverse across the isoclinal fold limbs suggesting that the pegmatites are syn-deformational and that they have been injected into fractures intrinsically linked to the fold development. Pegmatites are also deformed into asymmetric anticlinal folds above thrust structures and are cut by thrust structures. We also present data which demonstrates that the style of deformation changes with proximity to the major terrane-bounding thrust structure and that the pegmatites demonstrate classic imbricate style geometries on a regional scale related to regional transpression. This evidence suggests that the pegmatites are syn-deformational and were injected into thrust-related fractures and that the pegmatites are structurally related to Sveconorwegian fold geometries associated with peak metamorphism at approximately 1.14Ga. Deformation was

  3. Syn- and posteruptive hazards of maar diatreme volcanoes

    NASA Astrophysics Data System (ADS)

    Lorenz, Volker

    2007-01-01

    Maar-diatreme volcanoes represent the second most common volcano type on continents and islands. This study presents a first review of syn- and posteruptive volcanic and related hazards and intends to stimulate future research in this field. Maar-diatreme volcanoes are phreatomagmatic monogenetic volcanoes. They may erupt explosively for days to 15 years. Above the preeruptive surface a relatively flat tephra ring forms. Below the preeruptive surface the maar crater is incised because of formation and downward penetration of a cone-shaped diatreme and its root zone. During activity both the maar-crater and the diatreme grow in depth and diameter. Inside the diatreme, which may penetrate downwards for up to 2.5 km, fragmented country rocks and juvenile pyroclasts accumulate in primary pyroclastic deposits but to a large extent also as reworked deposits. Ejection of large volumes of country rocks results in a mass deficiency in the root zone of the diatreme and causes the diatreme fill to subside, thus the diatreme represents a kind of growing sinkhole. Due to the subsidence of the diatreme underneath, the maar-crater is a subsidence crater and also grows in depth and diameter with ongoing activity. As long as phreatomagmatic eruptions continue the tephra ring grows in thickness and outer slope angle. Syneruptive hazards of maar-diatreme volcanoes are earthquakes, eruption clouds, tephra fall, base surges, ballistic blocks and bombs, lahars, volcanic gases, cutting of the growing maar crater into the preeruptive ground, formation of a tephra ring, fragmentation of country rocks, thus destruction of area and ground, changes in groundwater table, and potential renewal of eruptions. The main hazards mostly affect an area 3 to possibly 5 km in radius. Distal effects are comparable to those of small eruption clouds from polygenetic volcanoes. Syneruptive effects on infrastructure, people, animals, vegetation, agricultural land, and drainage are pointed out. Posteruptive

  4. Salt flow direction and velocity during subsalt normal faulting and syn-kinematic sedimentation—implications from analytical calculations

    NASA Astrophysics Data System (ADS)

    Warsitzka, M.; Kukowski, N.; Kley, J.

    2018-04-01

    Salt flow induced by subsalt normal faulting is mainly controlled by tilting of the salt layer, the amount of differential loading due to syn-kinematic deposition, and tectonic shearing at the top or the base of the salt layer. Our study addresses the first two mechanisms and aims to examine salt flow patterns above a continuously moving subsalt normal fault and beneath a syn-kinematic minibasin. In such a setting, salt either tends to flow down towards the basin centre driven by its own weight or is squeezed up towards the footwall side owing to loading differences between the minibasin and the region above the footwall block. Applying isostatic balancing in analytical models, we calculated the steady-state flow velocity in a salt layer. This procedure gives insights into (1) the minimum vertical offset required for upward flow to occur, (2) the magnitude of the flow velocity, and (3) the average density of the supra-salt cover layer at the point at which upward flow starts. In a sensitivity study, we examined how the point of flow reversal and the velocity patterns are influenced by changes of the salt and cover layer thickness, the geometry of the cover flexure, the dip of the subsalt fault, compaction parameters of the supra-salt cover, the salt viscosity and the salt density. Our model results reveal that in most geological scenarios, salt flow above a continuously displacing subsalt normal fault goes through an early phase of downward flow. At sufficiently high fault offset in the range of 700-2600 m, salt is later squeezed upward towards the footwall side. This flow reversal occurs at smaller vertical fault displacement, if the thickness of the pre-kinematic layer is larger, the sedimentation rate of the syn-kinematic cover is higher, the compaction coefficient of cover sediments (i.e. the density increase with depth) is larger or the average density of the salt is lower. Other geometrical parameters such as the width of the cover monocline, the dip of the

  5. 1,3-syn-Diaxial Repulsion of Typical Protecting Groups Used in Carbohydrate Chemistry in 3-O-Substituted Derivatives of Isopropyl d-Idopyranosides.

    PubMed

    Komarova, Bozhena S; Gerbst, Alexey G; Finogenova, Anastasiia M; Dmitrenok, Andrey S; Tsvetkov, Yury E; Nifantiev, Nikolay E

    2017-09-01

    The strength of 1,3-syn-diaxial repulsion was evaluated for main types of protecting groups (alkyl, silyl, and acyl) usually used in carbohydrate chemistry. As molecular probes for this study, derivatives of isopropyl 2-O-benzyl-4,6-O-benzylidene-α-d-idopyranoside bearing allyl, acetyl, and tert-butyldiphenylsilyl (TBDPS) protecting groups at O-3 were prepared from p-methoxyphenyl d-galactopyranoside. The equilibrium between O S 2 and 4 C 1 conformations in these compounds was investigated using 3 J H,H and 3 J C,H coupling constants that were determined from 1D 1 H NMR and 2D J-resolved HMBC spectra in various solvents. The analysis of the corresponding coupling constants calculated using DFT/B3LYP/pcJ-1 approximation applied to conformations optimized at DFT/B3LYP/6-311++G** level supported the investigation. Proportions of conformers in the equilibrium revealed the highest repulsion between the 3-allyloxy group and the isopropoxy aglycon and its dependence on the solvent polarity. Differences in the conformational behavior of 3-O-allyl and 3-O-acetyl-α-d-idopyranoside derivatives complied with the notion that higher electron density on O-3 increased 1,3-syn-diaxial repulsion. 3-O-TBDPS derivative existed mainly in 4 C 1 conformation. The attenuation of the 1,3-syn-diaxial repulsive interaction indicates that TBDPS has stereoelectronic properties that may have significance in context of fixing unnatural pyranoside conformation with the help of silyl groups but have been disregarded until now.

  6. High-grade iron ore at Windarling, Yilgarn Craton: a product of syn-orogenic deformation, hypogene hydrothermal alteration and supergene modification in an Archean BIF-basalt lithostratigraphy

    NASA Astrophysics Data System (ADS)

    Angerer, Thomas; Hagemann, Steffen G.; Danyushevsky, Leonid

    2013-08-01

    Banded iron formation (BIF)-hosted iron ore deposits in the Windarling Range are located in the lower greenstone succession of the Marda-Diemals greenstone belt, Southern Cross domain, Yilgarn Craton and constitute a total hematite-martite-goethite ore resource of minimum 52 Mt at 60 wt.% Fe (0.07 P). Banded iron formation is interlayered with high-Mg basalts at Windarling and precipitated during episodes of volcanic quiescence. Trace element content and the rare earth element (REE) ratios Y/Ho (42 to 45), Sm/Yb (1.5), together with positive La and Gd anomalies in `least-altered' hematite-magnetite-metachert-BIF indicate the precipitation from Archean seawater that was fertilised by hydrothermal vent fluids with a basaltic HREE-Y signature. Hypogene iron ore in sub-greenschist facies metamorphosed BIF formed during three distinct stages: ore stage 1 was a syn- to post-metamorphic, syn-D1, Fe-Ca-Mg-Ni-Co-P-REE metasomatism that produced local Ni-REE-rich Fe-dolomite-magnetite alteration in BIF. Hydrothermal alteration was induced by hot fluid flow controlled by brittle-ductile reactivation of BIF-basalt margins and crosscutting D1 faults. The Ni-Co-rich content of dolomite and a shift in REE ratios in carbonate-altered BIF towards Archean mafic rock signature (Y/Ho to 31 to 40, Sm/Yb to 1 to 2 and Gd/Gd* to 1.2 to 1.4) suggest that high-Mg basalts in the Windarling Range were the primary source of introduced metals. During ore stage 2, a syn-deformational and likely acidic and oxidised fluid flow along BIF-basalt margins and within D1 faults leached carbonate and precipitated lepidoblastic and anhedral/granoblastic hematite. High-grade magnetite-hematite ore is formed during this stage. Ore stage 3 hydrothermal specular hematite (spcH)-Fe-dolomite-quartz alteration was controlled by a late-orogenic, brittle, compressional/transpressional stage (D4; the regional-scale shear-zone-related D3 is not preserved in Windarling). This minor event remobilised iron oxides

  7. Development of a Double Allylboration Reagent Targeting 1,5-syn-(E)-Diols: Application to the Synthesis of the C(23)-C(40) Fragment of Tetrafibricin

    PubMed Central

    Nuhant, Philippe; Kister, Jeremy; Lira, Ricardo; Sorg, Achim; Roush, William R.

    2011-01-01

    Interest in the synthesis of the C(23)-C(40) fragment 2 of tetrafibricin prompted us to develop a new method for the synthesis of 1,5-syn-(E)-diols. Toward this end, the kinetically controlled hydroboration of allenes 6, 33, ent-39, 42 and 45 with the Soderquist borane 25R were studied. Tetrabutylammonium allenyltrifluoroborate 45 gave superior results and was utilized in a double allylboration sequence with two different aldehydes to provide the targeted 1,5-syn-(E)-diols in generally high yields (72–98%), and with high enantioselectivity (>95% e.e.), diastereoselectivity (d.r. >20:1), and (E)/(Z) selectivity (>20:1). This new method was applied to the synthesis of the C(23)-C(40) fragment 2 of tetrafibricin. PMID:21857752

  8. Myceliophthora thermophila syn. Sporotrichum thermophile: a thermophilic mould of biotechnological potential.

    PubMed

    Singh, Bijender

    2016-01-01

    Myceliophthora thermophila syn. Sporotrichum thermophile is a ubiquitous thermophilic mould with a strong ability to degrade organic matter during optimal growth at 45 °C. Both genome analysis and experimental data have suggested that the mould is capable of hydrolyzing all major polysaccharides found in biomass. The mould is able to secrete a large number of hydrolytic enzymes (cellulases, laccases, xylanases, pectinases, lipases, phytases and some other miscellaneous enzymes) employed in various biotechnological applications. Characterization of the biomass-hydrolyzing activity of wild and recombinant enzymes suggests that this mould is highly efficient in biomass decomposition at both moderate and high temperatures. The native enzymes produced by the mould are more efficient in activity than their mesophilic counterparts beside their low enzyme titers. The mould is able to synthesize various biomolecules, which are used in multifarious applications. Genome sequence data of M. thermophila also supported the physiological data. This review describes the biotechnological potential of thermophilic mould, M. thermophila supported by genomic and experimental evidences.

  9. Diastereoselective oxidative α-amination of aliphatic aldehydes catalyzed by iodine: synthesis of syn-γ-hydroxy-α-amino acetals.

    PubMed

    Zhang, Yun-Xiao; Zhang, An-Qi; Tian, Jie-Sheng; Loh, Teck-Peng

    2013-12-28

    Aldehydes can react with secondary amines to give α-amino acetals via the α-amination of aliphatic aldehydes catalyzed by iodine. The presence of an asymmetric hydroxylated center at the γ-position of the aldehyde was found to induce the stereoselective amino group. This method represents a stereoselective α-amination of γ-hydroxyaldehydes for the synthesis of syn-γ-hydroxy-α-amino acetals in good yields and reasonable diastereoselectivities under very mild conditions.

  10. Syn-Fuel reciprocating charge pump improvement program. Quarterly technical project report, April-June 1984

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1984-01-01

    Major accomplishments during the second quarter of 1984 were completion of the Diaphragm Separation Seal clear liquid testing, and initiation of Phase III Field Testing. Diaphragm operational testing was conducted on a clear water test loop. The test goals were to ensure; mechanical reliability of the Diaphragm Seal, safe operation with simulated component failure, and proper operation of the Diaphragm Buffer Volume Control System. This latter system is essential in controlling the phasing of the diaphragm with its driving plunger. These tests were completed successfully. All operational problems were solved. However, it must be emphasized that the Diaphragm Seal wouldmore » be damaged by allowing the pump to operate in a cavitating condition for an extended period of time. A change in the Field Test phase of the program was made regarding choice of field test site. There is no operating Syn-Fuel pilot plant capable of inexpensively producing the slurry stream required for the reciprocating pump testing. The Field Tests will now be conducted by first testing the prototype pump and separation seals in an ambient temperature sand water slurry. This will determine resistence to abrasive wear and determine any operation problems at pressure over a lengthy period of time. After successful conclusion of these tests the pump and seals will be operated with a high temperature oil, but without solids, to identify any problems associated with thermal gradients, thermal shock and differential growth. After successful completion of the high temperature clean oil tests the pump will be deemed ready for in-line installation at a designated Syn-Fuel pilot plant. The above approach avoids the expense and complications of a separate hot slurry test loop. It also reduces risk of operational problems while in-line at the pilot plant. 5 figs.« less

  11. The effect of tectonic evolution on lacustrine syn-rift sediment patters in Qikou Sag, Bohaiwan Basin, eastern China

    NASA Astrophysics Data System (ADS)

    Liao, Y.; Wang, H.; Xu, W.

    2013-12-01

    Normal fault arrays and associated relay ramps between two overlapping en-echelon normal faults are well known to control the deposition and distribution of sediments in alluvial, fluvial and deltaic systems in rift settings. The influence of transfer zones or relay ramps on sediment routes and dispersal patterns in subaqueous (deeper marine/lacustrine), however, is barely studied and hence less clear. Previous experimental studies indicate that subaqueous relay ramps may act as sediment transportation pathways if certain conditions are available. In this study, we integrate detailed structural and stratigraphic analysis with three-dimensional seismic data and limited well log data from the Qikou Sag to examine the tectonic evolution and the syn-rift sediment patterns response to fault growth and linkage in an active rift setting. Qikou Sag is located at the center of Huanghua Depression, Bohaiwan Basin of eastern China. Structurally, it is a typical continental rift basin characterized by a linked system of two NEE-SWW-striking half-grabens and one E-W-striking graben. Qikou sag is filled with Eocene-Oligocene syn-rift sediments and Miocene to Quaternary post-rift sediments. The Eocene-Oligocene rifting stage can be divided into early rifting period (43-36.5 Ma, the third member and second member of Shahejie Formation, Es3 and Es2), stable rifting period (36.5-29Ma, the first member of Shaehejie Formation, Es1) and fault-depressed diversionary period (29-24.6Ma, the Dongying Formation, Ed). This study focus on the early syn-rift, the third and second member of Shehejie Formation, which is mostly dark-grey mudstone interbedded with fine to coarse-grained sandstone deposited by large-scale turbidity currents in deep-lake. In particular, we use a combination of thickness variability and facies distributions, onlap patterns within a high-resolution sequence stratigraphic framework, integrated with structural geometry, fault activity and subsidence history analysis to

  12. Crystal structures of complexes of the cys-syn-cys isomer of dicyclohexano-18-crown-6 with oxonium hexafluorotantalate and oxonium hexafluoroniobate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fonari, M. S.; Alekseeva, O. A.; Furmanova, N. G.

    2007-03-15

    The crystal structures of [(cys-syn-cys-dicyclohexano-18-crown-6 . H{sub 3}O)][TaF{sub 6}] and [(cys-syn-cys-dicyclohexano-18-crown-6 . H{sub 3}O)][NbF{sub 6}] complex compounds are determined using X-ray diffraction analysis. The tantalum complex has two polymorphic modifications, namely, the monoclinic (I) and triclinic (II) modifications. The unit cell parameters of these compounds are as follows: a = 8.507(4) A, b = 11.947(5) A, c = 27.392(12) A, {beta} = 93.11(1) deg., Z = 4, and space group P2{sub 1}/n for modification I; and a = 10.828(1) A, b = 11.204(1) A, c = 12.378(1) A, {alpha} = 72.12(1) deg., {beta} = 79.40(1) deg., {gamma} = 73.70(1) deg.,more » Z = 2, and space group P-1 for modification II. The triclinic niobium complex [(cys-syn-cys-dicyclohexano-18-crown-6 . H{sub 3}O)][NbF{sub 6}] (III) with the unit cell parameters a = 10.796(3) A, b = 11.183(3) A, c = 12.352(3) A, {alpha} = 72.364(5) deg., {beta} = 79.577(5) deg., {gamma} = 73.773(4) deg., Z = 2, and space group P-1 is isostructural with tantalum complex II. The structures of all three complexes are ionic in character. The oxonium cation in complexes I-III is encapsulated by the crown ether and thus forms one ordinary and two bifurcated hydrogen bonds with the oxygen atoms of the crown ether. This macrocyclic cation is bound to the anions through the C-H...F contacts (H...F, 2.48-2.58 A). The conformation of the macrocycle in complex I differs substantially from that in complex II (III)« less

  13. Organocatalysed asymmetric beta-amination and multicomponent syn-selective diamination of alpha,beta-unsaturated aldehydes.

    PubMed

    Jiang, Hao; Nielsen, Johanne B; Nielsen, Martin; Jørgensen, Karl Anker

    2007-01-01

    An easy and affordable route for obtaining chiral beta-aminated- and alpha,beta-diaminated aldehydes, 1,3-aminoalcohols, and related compounds by using organocatalysis is presented. The chiral secondary amine (S)-2-[bis(3,5-bistrifluoromethylphenyl)trimethylsilanyloxymethyl]pyrrolidine is used as the catalyst to activate alpha,beta-unsaturated aldehydes, which allows succinimide to add in a 1,4-regio- and stereoselective fashion thereby forming N-protected 1,3-aminoaldehydes in good yields and enantioselectivities. This is followed by two easy transformations giving rise to optically active 1,3-aminoalcohols, a common motif in many biologically active compounds, for example, fibrinogen receptor antagonists. Furthermore, optically active alpha,beta-syn-diaminated aldehydes were obtained by the addition of diethyl azodicarboxylate in a one-pot reaction.

  14. Episodic normal faulting and magmatism during the syn-spreading stage of the Baiyun sag in Pearl River Mouth Basin: response to the multi-phase seafloor spreading of the South China Sea

    NASA Astrophysics Data System (ADS)

    Deng, Peng; Mei, Lianfu; Liu, Jun; Zheng, Jinyun; Liu, Minghui; Cheng, Zijie; Guo, Fengtai

    2018-03-01

    Considerable post-breakup extensional deformation is recorded in the continental margins of the South China Sea (SCS). To recognize the nature and origin of the significant deformation during the syn-spreading stage (32-15.5 Ma) in the SCS, we comprehensively analyzed the geometry and kinematics of the faults and contemporaneous magmas in the Baiyun sag, northern margin of the SCS, using high-resolution regional three-dimensional seismic data. The kinematic analyses indicate that the faults in the Baiyun sag are recently formed following the onset of seafloor spreading in the SCS. The faults exhibit multiple episodes of growth history, with three active episodes, 32-29, 23.8-21 and 18.5-16.5 Ma, separated by periods of inactivity. Four volcanic groups comprising 98 volcanic mounds have been identified and described, located separately in the northwestern, the central, the southeastern and the northern slope areas. The occurrence of multiple palaeo-seafloors, complemented by the biostratigraphic and K-Ar dating data, reveals multiple extrusive events of the syn-spreading magmas in the Baiyun sag, with three active periods of 23.8-21, 18.5-17.5 and 17.5-16.5 Ma. This study confirms that the normal faulting has a shared genetic origin with the contemporaneous magmatism during the syn-spreading stage in the deep-offshore Baiyun sag, northern margin of the SCS. The episodic fault growth and magmatic extrusive events reveal that the Baiyun sag has undergone at least three episodic tectonic events during the syn-spreading stage, which evolved in response to the multi-stage seafloor spreading of the SCS.

  15. Matching conjugate volcanic rifted margins: 40Ar/ 39Ar chrono-stratigraphy of pre- and syn-rift bimodal flood volcanism in Ethiopia and Yemen

    NASA Astrophysics Data System (ADS)

    Ukstins, Ingrid A.; Renne, Paul R.; Wolfenden, Ellen; Baker, Joel; Ayalew, Dereje; Menzies, Martin

    2002-05-01

    40Ar/ 39Ar dating of mineral separates and whole-rock samples of rhyolitic ignimbrites and basaltic lavas from the pre- and syn-rift flood volcanic units of northern Ethiopia provides a temporal link between the Ethiopian and Yemen conjugate rifted volcanic margins. Sixteen new 40Ar/ 39Ar dates confirm that basaltic flood volcanism in Ethiopia was contemporaneous with flood volcanism on the conjugate margin in Yemen. The new data also establish that flood volcanism initiated prior to 30.9 Ma in Ethiopia and may predate initiation of similar magmatic activity in Yemen by ˜0.2-2.0 Myr. Rhyolitic volcanism in Ethiopia commenced at 30.2 Ma, contemporaneous with the first rhyolitic ignimbrite unit in Yemen at ˜30 Ma. Accurate and precise 40Ar/ 39Ar dates on initial rhyolitic ignimbrite eruptions suggest that silicic flood volcanism in Afro-Arabia post-dates the Oligocene Oi2 global cooling event, ruling out a causative link between these explosive silicic eruptions (with individual volumes ≥200 km 3) and climatic cooling which produced the first major expansion of the Antarctic ice sheets. Ethiopian volcanism shows a progressive and systematic younging from north to south along the escarpment and parallel to the rifted margin, from pre-rift flood volcanics in the north to syn-rift northern Main Ethiopian Rift volcanism in the south. A dramatic decrease in volcanic activity in Ethiopia between 25 and 20 Ma correlates with a prominent break-up unconformity in Yemen (26-19 Ma), both of which mark the transition from pre- to syn-rift volcanism (˜25-26 Ma) triggered by the separation of Africa and Arabia. The architecture of the Ethiopian margin is characterized by accumulation and preservation of syn-rift volcanism, while the Yemen margin was shaped by denudational unloading and magmatic starvation as the Arabian plate rifted away from the Afar plume. A second magmatic hiatus and angular unconformity in the northern Main Ethiopian Rift is evident at 10.6-3.2 Ma, and is

  16. The structure of the L3 loop from the hepatitis delta virus ribozyme: a syn cytidine.

    PubMed Central

    Lynch, S R; Tinoco, I

    1998-01-01

    The structure of the L3 central hairpin loop isolated from the antigenomic sequence of the hepatitis delta virus ribozyme with the P2 and P3 stems from the ribozyme stacked on top of the loop has been determined by NMR spectroscopy. The 26 nt stem-loop structure contains nine base pairs and a 7 nt loop (5'-UCCUCGC-3'). This hairpin loop is critical for efficient catalysis in the intact ribozyme. The structure was determined using homonuclear and heteronuclear NMR techniques on non-labeled and15N-labeled RNA oligonucleotides. The overall root mean square deviation for the structure was 1.15 A (+/- 0.28 A) for the loop and the closing C.G base pair and 0.90 A (+/- 0.18 A) for the loop and the closing C.G base pair but without the lone purine in the loop, which is not well defined in the structure. The structure indicates a U.C base pair between the nucleotides on the 5'- and 3'-ends of the loop. This base pair is formed with a single hydrogen bond involving the cytosine exocyclic amino proton and the carbonyl O4 of the uracil. The most unexpected finding in the loop is a syn cytidine. While not unprecedented, syn pyrimidines are highly unusual. This one can be confidently established by intranucleotide distances between the ribose and the base determined by NMR spectroscopy. A similar study of the structure of this loop showed a somewhat different three-dimensional structure. A discussion of differences in the two structures, as well as possible sites of interaction with the cleavage site, will be presented. PMID:9461457

  17. Highly Enantioselective Synthesis of syn-β-Hydroxy α-Dibenzylamino Esters via DKR Asymmetric Transfer Hydrogenation and Gram-Scale Preparation of Droxidopa.

    PubMed

    Sun, Guodong; Zhou, Zihong; Luo, Zhonghua; Wang, Hailong; Chen, Lei; Xu, Yongbo; Li, Shun; Jian, Weilin; Zeng, Jiebin; Hu, Benquan; Han, Xiaodong; Lin, Yicao; Wang, Zhongqing

    2017-08-18

    A highly efficient preparation of enantiomerically pure syn aryl β-hydroxy α-dibenzylamino esters is reported. The outcome was achieved via dynamic kinetic resolution and asymmetric transfer hydrogenation of aryl α-dibenzylamino β-keto esters. The desired products were obtained in high yields (up to 98%) with excellent diastereoselectivity (>20:1 dr) and enantioselectivity (up to >99% ee). Furthermore, this method was applied for the gram-scale preparation of droxidopa.

  18. Syn-extensional lithogenetic sequences of the Soledad basin, central Transverse Ranges: Implications for detachment-fault models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hendrix, E.D.

    1993-04-01

    The Soledad Basin (central Transverse Ranges, CA) contains the first recognized example of mid-Tertiary detachment-faulting west of the San Andreas fault. Displacements along the Pelona detachment fault and syn-extensional upper-plate sedimentation occurred between [approximately] 26--18 Ma, resulting in deposition of at least 4 separate lithogenetic sequences (LS) which record distinct phases of crustal response to extension. The 1st LS (lower Vasquez Fm.) predates syn-extensional volcanism and records initial basin subsidence along small, discontinuous faults. The 2nd LS (middle Vasquez Fm.) consists of both volcanic and sedimentary strata and signals simultaneous onset of magmatism and initial development of a well-defined networkmore » of high-angle, upper-plate normal faults, creating 2 separate sub-basins. Resulting alluvial fans were non-entrenched, implying that subsidence rates, and thus vertical displacement rates on high-angle faults, equaled or exceeded an estimated average sedimentation rate of 1.4 mm/yr. The 3rd LS (upper Vasquez Fm.) reflects transition to a single, well-integrated depositional basin characterized by streamflood sedimentation. This suggests an enlarged drainage basin and a decrease in subsidence rate relative to sedimentation rate, triggered possibly by uplift of the detachment lower-plate. The 4th LS (Tick Canyon Fm.) lies with angular unconformity above the 3rd LS and contains the 1st clasts eroded from the detachment lower plate. Detachment faulting in the Soledad basin appears to involve, in part, reactivation of structural zones of weakness along the Vincent thrust. Preliminary reconstructions of Soledad extension imply 25--30 km of displacement along the Pelona detachment fault system at an averaged slip rate of 3.6--4.3 mm/yr.« less

  19. Mafic enclaves record syn-eruptive basalt intrusion and mixing

    NASA Astrophysics Data System (ADS)

    Plail, Melissa; Edmonds, Marie; Woods, Andrew W.; Barclay, Jenni; Humphreys, Madeleine C. S.; Herd, Richard A.; Christopher, Thomas

    2018-02-01

    Mafic enclaves hosted by andesite erupted at the Soufrière Hills Volcano between 1995 and 2010 yield insights into syn-eruptive mafic underplating of an andesite magma reservoir, magma mixing and its role in sustaining eruptions that may be widely applicable in volcanic arc settings. The mafic enclaves range in composition from basalt to andesite and are generated from a hybrid thermal boundary layer at the interface between the two magmas, where the basalt quenches against the cooler andesite, and the two magmas mix. We show, using an analytical model, that the enclaves are generated when the hybrid layer, just a few tens of centimetres thick, becomes buoyant and forms plumes which rise up into the andesite. Mafic enclave geochemistry suggests that vapour-saturated basalt was underplated quasi-continuously throughout the first three eruptive phases of the eruption (the end member basalt became more Mg and V-rich over time). The andesite erupted during the final phases of the eruption contained more abundant and larger enclaves, and the enclaves were more extensively hybridised with the andesite, suggesting that at some time during the final few years of the eruption, the intrusion of mafic magma at depth ceased, allowing the hybrid layer to reach a greater thickness, generating larger mafic enclaves. The temporal trends in mafic enclave composition and abundance suggests that basalt recharge and underplating sustained the eruption by the transfer of heat and volatiles across the interface and when the recharge ceased, the eruption waned. Our study has important implications for the petrological monitoring of long-lived arc eruptions.

  20. Ultrafast syn-eruptive degassing and ascent trigger high-energy basic eruptions.

    PubMed

    Giuffrida, Marisa; Viccaro, Marco; Ottolini, Luisa

    2018-01-09

    Lithium gradients in plagioclase are capable of recording extremely short-lived processes associated with gas loss from magmas prior to extrusion at the surface. We present SIMS profiles of the 7 Li/ 30 Si ion ratio in plagioclase crystals from products of the paroxysmal sequence that occurred in the period 2011-2013 at Mt. Etna (Italy) in an attempt to constrain the final ascent and degassing processes leading to these powerful eruptions involving basic magma. The observed Li concentrations reflect cycles of Li addition to the melt through gas flushing, and a syn-eruptive stage of magma degassing driven by decompression that finally produce significant Li depletion from the melt. Modeling the decreases in Li concentration in plagioclase by diffusion allowed determination of magma ascent timescales that are on the order of minutes or less. Knowledge of the storage depth beneath the volcano has led to the quantification of a mean magma ascent velocity of ~43 m/s for paroxysmal eruptions at Etna. The importance of these results relies on the application of methods, recently used exclusively for closed-system volcanoes producing violent eruptions, to open-conduit systems that have generally quiet eruptive periods of activity sometimes interrupted by sudden re-awakening and the production of anomalously energetic eruptions.

  1. Rhodium-catalysed syn-carboamination of alkenes via a transient directing group.

    PubMed

    Piou, Tiffany; Rovis, Tomislav

    2015-11-05

    Alkenes are the most ubiquitous prochiral functional groups--those that can be converted from achiral to chiral in a single step--that are accessible to synthetic chemists. For this reason, difunctionalization reactions of alkenes (whereby two functional groups are added to the same double bond) are particularly important, as they can be used to produce highly complex molecular architectures. Stereoselective oxidation reactions, including dihydroxylation, aminohydroxylation and halogenation, are well established methods for functionalizing alkenes. However, the intermolecular incorporation of both carbon- and nitrogen-based functionalities stereoselectively across an alkene has not been reported. Here we describe the rhodium-catalysed carboamination of alkenes at the same (syn) face of a double bond, initiated by a carbon-hydrogen activation event that uses enoxyphthalimides as the source of both the carbon and the nitrogen functionalities. The reaction methodology allows for the intermolecular, stereospecific formation of one carbon-carbon and one carbon-nitrogen bond across an alkene, which is, to our knowledge, unprecedented. The reaction design involves the in situ generation of a bidentate directing group and the use of a new cyclopentadienyl ligand to control the reactivity of rhodium. The results provide a new way of synthesizing functionalized alkenes, and should lead to the convergent and stereoselective assembly of amine-containing acyclic molecules.

  2. Human primitive meninges in and around the mesencephalic flexure and particularly their topographical relation to cranial nerves.

    PubMed

    Cho, Kwang Ho; Rodríguez-Vázquez, Jose Francisco; Han, Eui Hyeog; Verdugo-López, Samuel; Murakami, Gen; Cho, Baik Hwan

    2010-09-20

    Development of the meninges in and around the plica ventralis encephali has not been well documented. A distinct mesenchymal structure, the so-called plica ventralis encephali, is sandwiched by the fetal mesencephalic flexure. We histologically examined paraffin-embedded sections from 18 human embryos and fetuses at 6-12 weeks of gestation. In the loose tissues of the plica, the first meninx appeared as a narrow membrane along the oculomotor nerve at 7-8 weeks. Subsequently, the plica ventralis evolved into 3 parts: bilateral lateral mesenchymal condensations and a primitive membranous meninx extending between. Notably, the topographical anatomy of the oculomotor, trochlear and trigeminal nerves did not change: the oculomotor nerve ran along the rostral aspect of the membranous meninx, the trigeminal nerve ran along the caudal side of the lateral mesenchymal condensation, and the trochlear nerve remained embedded in the lateral condensation. Up to 9-10 weeks, the lateral mesenchymal condensations became tongue-like folds; i.e., the primitive form of the tentorium cerebelli, while the membranous meninx became the diaphragma sellae. The falx cerebri seemed to develop from the tongue-like folds. Overall, the final tentorium cerebelli corresponded to the regressed plica ventralis, while the parasellar area originated from the base of the plica and other tissues along the ventral aspects of the basisphenoid and basioccipital. Copyright © 2010 Elsevier GmbH. All rights reserved.

  3. Syn-pandemic Fire Suppression in the Tropical Americas During European Conquest

    NASA Astrophysics Data System (ADS)

    Nevle, R. J.; Bird, D. K.

    2006-12-01

    punctuated by three intervals of low charcoal accumulation, reflecting intermittent episodes of fire-suppression lasting <200 years. The latest and most pronounced of these low-fire intervals occurs at ~1100 years BP and corresponds to the Classic Maya collapse. The persistence of low charcoal accumulation rates for several centuries after ~500 years BP is parsimoniously explained by a reduction of agriculture-related biomass burning due to syn-pandemic population collapse. During European conquest, pandemics killed ~90% of the indigenous American population, estimated to represent ~20% of the 16^{th} century global population. The suppression of biomass burning after ~500 years BP is a unique feature of the fire history of Central and equatorial South America relative to other regions of the globe, where rates of charcoal accumulation are typically >0.2 s.d. above their Holocene mean values. Syn-pandemic fire suppression in the tropical Americas is associated with massive regional reforestation and sequestration of carbon into the terrestrial biosphere, which contributed to the ~2% global reduction in atmospheric CO2 levels and the 0.1 per mil increase in δ13C of atmospheric CO2 from 1500 to 1700 A.D.

  4. Enantioselective synthesis of syn/anti-1,3-amino alcohols via proline-catalyzed sequential alpha-aminoxylation/alpha-amination and Horner-Wadsworth-Emmons olefination of aldehydes.

    PubMed

    Jha, Vishwajeet; Kondekar, Nagendra B; Kumar, Pradeep

    2010-06-18

    A novel and general method for asymmetric synthesis of both syn/anti-1,3-amino alcohols is described. The method uses proline-catalyzed sequential alpha-aminoxylation/ alpha-amination and Horner-Wadsworth-Emmons (HWE) olefination of aldehydes as the key step. By using this method, a short synthesis of a bioactive molecule, (R)-1-((S)-1-methylpyrrolidin-2-yl)-5-phenylpentan-2-ol, is also accomplished.

  5. Ductile strain rate recorded in the Symvolon syn-extensional plutonic body (Rhodope core complex, Greece)

    NASA Astrophysics Data System (ADS)

    Cirrincione, Rosolino; Fazio, Eugenio; Ortolano, Gaetano; Fiannacca, Patrizia; Kern, Hartmut; Mengel, Kurt; Pezzino, Antonino; Punturo, Rosalda

    2016-04-01

    The present contribution deals with quantitative microstructural analysis, which was performed on granodiorites of the syn-tectonic Symvolon pluton (Punturo et al., 2014) at the south-western boundary of the Rhodope Core Complex (Greece). Our purpose is the quantification of ductile strain rate achieved across the pluton, by considering its cooling gradient from the centre to the periphery, using the combination of a paleopiezometer (Shimizu, 2008) and a quartz flow law (Hirth et al., 2001). Obtained results, associated with a detailed cooling history (Dinter et al., 1995), allowed us to reconstruct the joined cooling and strain gradient evolution of the pluton from its emplacement during early Miocene (ca. 700°C at 22 Ma) to its following cooling stage (ca. 500-300°C at 15 Ma). Shearing temperature values were constrained by means of a thermodynamic approach based on the recognition of syn-shear assemblages at incremental strain; to this aim, statistical handling of mineral chemistry X-Ray maps was carried out on microdomains detected at the tails of porphyroclasts. Results indicate that the strain/cooling gradients evolve "arm in arm" across the pluton, as also testified by the progressive development of mylonitic fabric over the magmatic microstructures approaching the host rock. References • Dinter, D. A., Macfarlane, A., Hames, W., Isachsen, C., Bowring, S., and Royden, L. (1995). U-Pb and 40Ar/39Ar geochronology of the Symvolon granodiorite: Implications for the thermal and structural evolution of the Rhodope metamorphic core complex, northeastern Greece. Tectonics, 14 (4), 886-908. • Shimizu, I. (2008). Theories and applicability of grain size piezometers: The role of dynamic recrystallization mechanisms. Journal of Structural Geology, 30 (7), 899-917. • Hirth, G., Teyssier, C., and Dunlap, J. W. (2001). An evaluation of quartzite flow laws based on comparisons between experimentally and naturally deformed rocks. International Journal of Earth

  6. Efficient Synthesis of Differentiated syn-1,2-Diol Derivatives by Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution of α-Alkoxy-Substituted β-Ketoesters.

    PubMed

    Monnereau, Laure; Cartigny, Damien; Scalone, Michelangelo; Ayad, Tahar; Ratovelomanana-Vidal, Virginie

    2015-08-10

    Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl α-alkoxy-β-ketoesters in the presence of well-defined, commercially available, chiral catalyst Ru(II) -(N-p-toluenesulfonyl-1,2-diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn α-alkoxy-β-hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.)>99:1) and an almost perfect enantioselectivity (enantiomeric excess (ee)>99 %). Additionally, after extensive screening of the reaction conditions, the use of Ru(II) - and Rh(III) -tethered precatalysts extended this process to more-challenging substrates that bore alkenyl-, alkynyl-, and alkyl substituents to provide the corresponding syn α-alkoxy-β-hydroxyesters with excellent enantiocontrol (up to 99 % ee) and good to perfect diastereocontrol (d.r.>99:1). Lastly, the synthetic utility of the present protocol was demonstrated by application to the asymmetric synthesis of chiral ester ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)-propanoate, which is an important pharmacophore in a number of peroxisome proliferator-activated receptor α/γ dual agonist advanced drug candidates used for the treatment of type-II diabetes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Modeling the Syn-Disposition of Nitrogen Donors in Non-Heme Diiron Enzymes. Synthesis, Characterization, and Hydrogen Peroxide Reactivity of Diiron(III) Complexes with the Syn N-Donor Ligand H2BPG2DEV

    PubMed Central

    Friedle, Simone; Kodanko, Jeremy J.; Morys, Anna J.; Hayashi, Takahiro; Moënne-Loccoz, Pierre; Lippard, Stephen J.

    2009-01-01

    In order to model the syn disposition of histidine residues in carboxylate-bridged non-heme diiron enzymes, we prepared a new dinucleating ligand, H2BPG2DEV, that provides this geometric feature. The ligand incorporates biologically relevant carboxylate functionalities, which have not been explored as extensively as nitrogen-only analogs. Three novel oxo-bridged diiron(III) complexes [Fe2(μ-O)(H2O)2-(BPG2DEV)](ClO4)2 (6), [Fe2(μ-O)(μ-O CAriPrO)(BPG2DEV)](ClO4) (7), and [Fe2(μ-O)(μ-CO3)(BPG2DEV)] (8) were prepared. Single crystal X-ray structural characterization confirms that two pyridines are bound syn with respect to the Fe–Fe vector in these compounds. The carbonato-bridged complex 8 forms quantitatively from 6 in a rapid reaction with gaseous CO2 in organic solvents. A common maroon-colored intermediate (λmax = 490 nm; ε = 1500 M−1 cm−1) forms in reactions of 6, 7, or 8 with H2O2 and NEt3 in CH3CN/H2O solutions. Mass spectrometric analyses of this species, formed using 18O-labeled H2O2, indicate the presence of a peroxide ligand bound to the oxo-bridged diiron(III) center. The Mössbauer spectrum at 90 K of the EPR-silent intermediate exhibits a quadrupole doublet with δ. = 0.58 mm/s and ΔEQ = 0.58 mm/s. The isomer shift is typical for a peroxodiiron(III) species, but the quadrupole splitting parameter is unusually small compared to related complexes. These Mössbauer parameters are comparable to those observed for a peroxo intermediate formed in the reaction of reduced toluene/o-xylene monooxygenase hydroxylase (ToMOH) with dioxygen. Resonance Raman studies reveal an unusually low-energy O–O stretching mode in the peroxo intermediate that is consistent with a short diiron distance. Although peroxodiiron(III) intermediates generated from 6, 7, and 8 are poor O-atom transfer catalysts, they display highly efficient catalase activity, with turnover numbers up to 10,000. In contrast to hydrogen peroxide reactions of diiron(III) complexes that lack

  8. 3-D ore body modeling and structural settings of syn-to late orogenic Variscan hydrothermal mineralization, Siegerland district, Rhenish Massif, NW Germany

    NASA Astrophysics Data System (ADS)

    Peters, Meike; Hellmann, André; Meyer, Franz Michael

    2013-04-01

    The Siegerland district is located in the fold-and thrust-belt of the Rhenish Massif and hosts diverse syn-to late orogenic mineralization styles. Peak-metamorphism and deformation occurred at 312-316±10 Ma (Ahrendt et al., 1978) at temperature-pressure conditions of 280-320°C and 0.7-1.4 kbar (Hein, 1993). In addition to syn-orogenic siderite-quartz mineralization at least four different syn-to late orogenic mineralization stages are identified comprising Co-Ni-Cu-Au, Pb-Zn-Cu, Sb-Au, and hematite-digenite-bornite ores (Hellmann et al., 2012). The earliest type of syn-orogenic ore mineralization is formed by siderite-quartz veins, trending N-S, E-W and NE-SW. The vein systems are closely related to fold and reverse fault geometries (Hellmann et al., 2012). The most important structural feature is the first-order Siegen main reverse fault showing an offset into three major faults (Peters et al., 2012). The structural control on ore formation is demonstrated by the Co-Ni-Cu-Au mineralization generally hosted by NE-ENE trending reverse faults and associated imbrication zones that have reactivated the older siderite-quartz veins. In this study, we developed a 3-D model of the Alte Buntekuh ore bodies in the Siegerland district, using Datamine Studio3 to investigate the structural setting of Co-Ni-Cu-Au mineralization. The salient structural and spatial data for the 3-D model were taken from old mine level plans as well as from geological and topographical maps. The ore bodies are located immediately in the hanging wall of the southern branch of the Siegen main reverse fault (Peters et al., 2012). From the model it becomes obvious, that the earlier siderite-quartz veins, dipping steeply to the NW, are cross-cut and segmented by oppositely dipping oblique reverse faults. Individual ore body segments are rotated and displaced, showing a plunge direction to the SW. The 3-D model further reveals the presence of hook-like, folded vein arrays, highly enriched in cobalt

  9. [Sublingual structures of primates. II. Hominoidea, review, summary and literature].

    PubMed

    Rommel, C

    1981-01-01

    1. In Homo and the great apes (Pongidae) there occurs, besides the plica sublingualis a plica fimbriata at the ventral surface of the tongue. This duplicature of the mucosa does not occur in the Hylobytidae and in the other primates. 2. Some taste buds could be found in the epithelium of the plica sublingualis of the Pongidae. 3. There are many taste buds in the epithelium of the plica fimbriata of the Pongidae. On this sublingual structure there were counted 1776 taste buds in Pongo, 592 in Gorilla and 280 in Pan. A few taste buds could also be found on the plica fimbriata of a human newborn. 4. A glandula apicis linguae occurs in Homo, Pan, Gorilla and Pongo. 5. The fresh saliva of the glandula apicis linguae and the saliva on the floor of the mouth can be tested by the taste buds in the epithelium of the plica fimbriata, of papillae lenticulares and of areae gustatoriae at the ventral surface of the tongue. 6. It might be the function of the sublingual taste buds to taste the fresh saliva as a gradient for the central nervous comparison with the taste of the saliva on the dorsal surface of the tongue. 7. Because of the complete absence of a sublingua in the Platyrrhini and in the Cercopithecinae it is unlikely that the plica fimbriata of Homo and the great apes can be interpreted as a homalogon of the sublingua in the prosimians. 8. Because of the absence of a sublingua in other ordines of the Mammalia (Insectivora, Carnivora, Rodentia, Chiroptera, Ungulata) it is unlikely as well that the sublingua in the prosimians can be interpreted as a homologon of the tongues of the lower vertebrates. The sublingual structures occuring in the Marsupialia have to be investigated. 9. Because of these reasons the new development of the sublingua in the prosimians and the plica fimbriata in the Hominoidea, in complete independence from one another, seems to be a better explanation of the 2 structures and less contradictionary to anatomical and phylogenetic arguments. The

  10. The development of the genital peritoneum in domestic mammals. An analysis of the literature and nomenclature.

    PubMed

    Martin, E

    1995-12-01

    This review presents and discusses the reasons for the currently employed anatomical terminology relating to the genital peritoneum of various domestic species, based upon its prenatal development. When reviewing the development of genital organs, attention must be paid to changes in the related peritoneum in order to define currently used terminology more clearly. The relevance of some terms such as Caudal genital ligament, Plica gubernaculi, Plica iguinalis and genital fold is considered. A system of serosal folds, the Plica gonadoinguinalis or genitoinguinalis, seems to be a useful term to be added to the Nomina Embryologica Veterinaria.

  11. [1,5]-Anion relay via intramolecular proton transfer to generate 3,3-bis(silyl) allyloxy lithium: a useful scaffold for syn-addition to aldehydes and ketones.

    PubMed

    Lin, Xinglong; Ye, Xincui; Sun, Xianwei; Zhang, Yuebao; Gao, Lu; Song, Zhenlei

    2014-02-21

    A [1,5]-anion relay has been achieved in 3,3-bis(silyl) benzyl enol ether. Deprotonation at the sterically more accessible benzyl position triggers an intramolecular proton transfer to generate the thermodynamically more stable 3,3-bis(silyl) allyloxy lithium. This endo-oriented allyl anion is stable at -78 °C and undergoes diastereoselective syn-addition at the γ-position with aldehydes and ketones to give monobenzyl-substituted 1,2-diols.

  12. Crustal processes cause adakitic chemical signatures in syn-collision magmatism from SE Iran

    NASA Astrophysics Data System (ADS)

    Allen, Mark; Kheirkhah, Monireh; Neill, Iain

    2015-04-01

    We report new elemental and Nd-Sr isotopic analyses for Late Cenozoic intrusive and extrusive rocks emplaced in SE Iran as part of the wider syn-collision magmatic province within the Turkish-Iranian Plateau. The sample sites are near the town of Dehaj in Kerman Province. Most of the rocks are from stocks and batholiths, interpreted as the roots of central volcanoes. Age controls are not precise, but the rocks are likely to be Late Miocene-Quaternary in age. Basaltic to andesitic lavas crop out nearby; their relationships to the intrusive rocks are uncertain. Geochemically, the entire range of rocks from basalt lavas through to rhyolitic intrusives ranges from 51-71 wt.% silica and isotopic signatures are similar to Bulk Earth, without any clear evidence for large-scale crustal contamination. The basaltic to andesitic lavas appear to have variable and often high La/Yb and Sr/Y such that they range from calc-alkaline arc-like rocks to adakitic compositions depending on the degree of fractionation. The intrusive rocks seem to form a separate suite, with clear indications of increasing Sr/Y and Dy/Yb with fractionation. Previous interpretations relate adakitic magmatism to Tethyan oceanic slab break-off and slab melting beneath the collision zone. However, as the 'adakitic signature' is increasingly apparent in more evolved magmas, at least in the intrusives, adakite generation is more likely to have occurred during melt evolution from an initial low Sr/Y and low La/Yb parent. This parental melt may have been similar in starting composition to proposed non-adakitic basaltic melts from elsewhere in the collision zone. The high Sr/Yb and La/Yb signatures are best explained by the suppression of plagioclase fractionation by high magmatic water contents, promoting incompatible behaviour of Sr. Conversely, Y and Yb are compatible during amphibole and garnet fractionation at crustal or uppermost mantle levels. Rather than a localised slab break-off or melting effect, the

  13. Interactions between ethanol, syn-2,3-hexanediol, 3-hydroxyhexan-2-one, and 3-hydroxyoctan-2-one lures on trap catches of hardwood longhorn beetles in southeastern united states

    Treesearch

    D R Miller; C M Crowe; P D Mayo; L S Reid; P J Silk; J D Sweeney

    2017-01-01

    The effectiveness of a four-component “super lure” consisting of ethanol (E) and the cerambycid pheromones syn-2,3-hexanediol (D6), racemic 3-hydroxyhexan-2-one (K6), and racemic 3-hydroxyoctan-2-one (K8) on trap catches of Cerambycidae (Coleoptera) was determined in southeast United States with seven trapping experiments in 2011–2013. We captured...

  14. Ductile extension of syn-magmatic lower crusts, with application to volcanic passive margins: the Ivrea Zone (Southern Alps, Italy)

    NASA Astrophysics Data System (ADS)

    Bidault, Marie; Geoffroy, Laurent; Arbaret, Laurent; Aubourg, Charles

    2017-04-01

    Deep seismic reflection profiles of present-day volcanic passive margins often show a 2-layered lower crust, from top to bottom: an apparently ductile 12 km-thick middle-lower layer (LC1) of strong folded reflectors and a 4 km-thick supra-Moho layer (LC2) of horizontal and parallel reflectors. Those layers appear to be structurally disconnected and to develop at the early stages of margins evolution. A magmatic origin has been suggested by several studies to explain those strong reflectors, favoring mafic sills intrusion hypothesis. Overlying mafic and acidic extrusives (Seaward Dipping Reflectors sequences) are bounded by continentward-dipping detachment faults rooting in, and co-structurated with, the ductile part of the lower crust (LC1). Consequently the syn-rift to post-rift evolution of volcanic passive margins (and passive margins in general) largely depends on the nature and the properties of the lower crust, yet poorly understood. We propose to investigate the properties and rheology of a magma-injected extensional lower crust with a field analogue, the Ivrea Zone (Southern Alps, Italy). The Ivrea Zone displays a complete back-thrusted section of a Variscan continental lower crust that first underwent gravitational collapse, and then lithospheric extension. This Late Paleozoic extension was apparently associated with the continuous intrusion of a large volume of mafic to acid magma. Both the magma timing and volume, and the structure of the Ivrea lower crust suggest that this section represents an adequate analogue of a syn-magmatic in-extension mafic rift zone which aborted at the end of the Permian. Notably, we may recognize the 2 layers LC1 and LC2. From a number of tectonic observations, we reconstitute the whole tectonic history of the area, focusing on the strain field evolution with time, in connection with mafic magma injection. We compare those results with available data from extensional mafic lower crusts at rifts and margins.

  15. Syn-emplacement fracturing in the Sandfell laccolith, eastern Iceland – implications for rhyolite intrusion growth and volcanic hazards

    NASA Astrophysics Data System (ADS)

    Mattsson, Tobias; Burchardt, Steffi; Almqvist, Bjarne S. G.; Ronchin, Erika

    2018-02-01

    Felsic magma commonly pools within shallow mushroom-shaped magmatic intrusions, so-called laccoliths or cryptodomes, which can cause both explosive eruptions and collapse of the volcanic edifice. Deformation during laccolith emplacement is primarily considered to occur in the host rock. However, shallowly emplaced laccoliths (cryptodomes) show extensive internal deformation. While deformation of magma in volcanic conduits is an important process for regulating eruptive behavior, the effects of magma deformation on intrusion emplacement remain largely unexplored. In this study, we investigate the emplacement of the 0.57 km3 rhyolitic Sandfell laccolith, Iceland, which formed at a depth of 500 m in a single intrusive event. By combining field measurements, 3D modeling, anisotropy of magnetic susceptibility, microstructural analysis, and FEM modeling we examine deformation in the magma to constrain its influence on intrusion emplacement. Concentric flow bands and S-C fabrics reveal contact-parallel magma flow during the initial stages of laccolith inflation. The magma flow fabric is overprinted by strain-localization bands and more than one third of the volume of the Sandfell laccolith display concentric intensely fractured layers. A dominantly oblate magmatic fabric in the fractured areas and conjugate geometry of strain-localization bands, and fractures in the fracture layers demonstrate that the magma was deformed by intrusive stresses. This implies that a large volume of magma became viscously stalled and was unable to flow during intrusion. Fine-grained groundmass and vesicle-poor rock adjacent to the fracture layers point to that the interaction between the strain-localization bands and the flow bands at sub-solidus state caused the brittle-failure and led to decompression degassing and crystallization and rapid viscosity increase in the magma. The extent of syn-emplacement fracturing in the Sandfell laccolith further shows that strain-induced degassing limited

  16. Physiological Characterization of the SynCardia Total Artificial Heart in a Mock Circulation System

    PubMed Central

    Crosby, Jessica R.; DeCook, Katrina J.; Tran, Phat L.; Smith, Richard G.; Larson, Douglas F.; Khalpey, Zain I.; Burkhoff, Daniel; Slepian, Marvin J.

    2014-01-01

    The SynCardia total artificial heart (TAH) has emerged as an effective, life-saving bi-ventricular replacement system for a wide variety of patients with end-stage heart failure. While the clinical performance of the TAH is established, modern physiologic characterization, in terms of elastance behavior and pressure-volume characterization has not been defined. Herein we examine the TAH in terms of elastance using a non-ejecting left-ventricle, and then characterize the pressure-volume relationship of the TAH by varying preload and afterload parameters using a Donovan Mock Circulatory System. We demonstrate that the TAH does not operate with time-varying elastance, differing from the human heart. Further, we show that the TAH has a pressure-volume relationship behavior that also differs from that of the human heart. The TAH does exhibit Starling-like behavior, with output increasing via preload dependent mechanisms, without reliance on an alteration of inotropic state within the operating window of the TAH. Within our testing range, the TAH is insensitive to variations in afterload, however this insensitivity has a limit, the limit being the maximum driving pressure of the pneumatic driver. Understanding the physiology of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared to the human heart. PMID:25551416

  17. Physiological characterization of the SynCardia total artificial heart in a mock circulation system.

    PubMed

    Crosby, Jessica R; DeCook, Katrina J; Tran, Phat L; Smith, Richard G; Larson, Douglas F; Khalpey, Zain I; Burkhoff, Daniel; Slepian, Marvin J

    2015-01-01

    The SynCardia total artificial heart (TAH) has emerged as an effective, life-saving biventricular replacement system for a wide variety of patients with end-stage heart failure. Although the clinical performance of the TAH is established, modern physiological characterization, in terms of elastance behavior and pressure-volume (PV) characterization has not been defined. Herein, we examine the TAH in terms of elastance using a nonejecting left ventricle, and then characterize the PV relation of the TAH by varying preload and afterload parameters using a Donovan Mock Circulatory System. We demonstrate that the TAH does not operate with time-varying elastance, differing from the human heart. Furthermore, we show that the TAH has a PV relation behavior that also differs from that of the human heart. The TAH does exhibit Starling-like behavior, with output increasing via preload-dependent mechanisms, without reliance on an alteration of inotropic state within the operating window of the TAH. Within our testing range, the TAH is insensitive to variations in afterload; however, this insensitivity has a limit, the limit being the maximum driving pressure of the pneumatic driver. Understanding the physiology of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared with the human heart.

  18. The crustal characteristics at syn- and/or post-rifting in eastern Shikoku basin by seismic reflection survey

    NASA Astrophysics Data System (ADS)

    Yamashita, M.; Takahashi, N.; Kodaira, S.; Takizawa, K.; No, T.; Miura, S.; Kaneda, Y.

    2008-12-01

    Imaging of the arc-backarc transition zone is important in relation to the backarc opening process. Shikoku Basin locates between the Kyushu-Palau Ridge and the Izu-Ogasawara Arc, which is an important area to reveal the opening evolution of the backarc basins as a part of the growth process of the Philippine Sea. The Shikoku Basin was in the backarc rifting and spreading stage during about 30-15 Ma (e.g. Okino et al., 1994). High P-wave velocity lower crust is identified in arc-backarc transition zone by refraction survey using OBSs (Takahashi et al., 2007). Japan Agency for Marine-Earth Science and Technology (JAMSTEC) carried out multi-channel seismic reflection (MCS) survey using 12,000 cu.in. air gun and 5 km streamer with 204 ch hydrophones in the Izu-Ogasawara region since 2004. We extracted and mapped the crustal characteristics from poststack and prestack depth migrated profiles. According to obtained profiles, the deformation structure with share component is recognized in arc-backarc transition zone, which located eastern side of Shikoku Basin from Zenisu Ridge to about 500 km south. The maximum width of this deformation zone is about 100 km. The relative displacement of horizon is little; however, it is strongly deformed from upper crust beneath seafloor. This deformation zone indicates the post- rifting activity in east side of Shikoku Basin. On the other hand, some knolls are indicated along the en- echelon arrangement from Izu-Ogasawara arc. Ishizuka et al. (2003) reported post-rifting volcanism with Miocene age in en-echelon arrangement. A part of these knolls are estimated to penetrate at syn-rifting and/or post-rifting stage in backarc opening. By comparing the both side of arc-backarc transition zone, we elucidate syn- and post-rifting effect in Shikoku Basin. We also carried out high density MCS surveys in Shikoku Basin in order to IODP proposal site for reconstruction of magmatic processes since Oligocene in rear arc. In this survey, we use new

  19. Experience with the SynCardia total artificial heart in a Canadian centre

    PubMed Central

    Nguyen, Anthony; Pellerin, Michel; Perrault, Louis P.; White, Michel; Ducharme, Anique; Racine, Normand; Carrier, Michel

    2017-01-01

    Background The SynCardia total artificial heart (TAH) provides complete circulatory support by replacing both native ventricles. Accepted indications include bridge to transplantation and destination therapy. We review our experience with TAH implantation during a period when axial flow pump became available. Methods We retrospectively analyzed the demographics, clinical characteristics and survival of all patients receiving the TAH. Results From September 2004 to November 2016, 13 patients (12 men, mean age 45 ± 13 yr) received the TAH for refractory cardiogenic shock secondary to idiopathic (56%) or ischemic (17%) cardiomyopathy and to other various causes (33%). Before implantation, mean ejection fraction was 14% ± 4%, 7 (54%) patients had previous cardiac surgery, 4 (31%) were on mechanical ventilation, and 3 (23%) patients were on dialysis. The mean duration of TAH support was 46 ± 40 days. Three (23%) patients died while on support after a mean of 15 days. Actuarial survival on support was 77% ± 12% at 30 days after implantation. Complications on support included stroke (n = 1, 8%), acute respiratory distress syndrome requiring prolonged intubation (n = 5, 38%) and acute renal failure requiring temporary dialysis (n = 5, 38%). Ten (77%) patients survived to be transplanted after a mean of 52 ± 42 days of support. Actuarial survival rates after transplant were 67% ± 16% at 1 month and 56% ± 17% at 1 year after transplantation. Conclusion The TAH provides an alternative with low incidence of neurologic events in extremely fragile and complex patients waiting for heart transplantation. Complex and unusual anatomic conditions explained the current use of TAH. PMID:28930049

  20. Experience with the SynCardia total artificial heart in a Canadian centre.

    PubMed

    Nguyen, Anthony; Pellerin, Michel; Perrault, Louis P; White, Michel; Ducharme, Anique; Racine, Normand; Carrier, Michel

    2017-12-01

    The SynCardia total artificial heart (TAH) provides complete circulatory support by replacing both native ventricles. Accepted indications include bridge to transplantation and destination therapy. We review our experience with TAH implantation during a period when axial flow pump became available. We retrospectively analyzed the demographics, clinical characteristics and survival of all patients receiving the TAH. From September 2004 to November 2016, 13 patients (12 men, mean age 45 ± 13 yr) received the TAH for refractory cardiogenic shock secondary to idiopathic (56%) or ischemic (17%) cardiomyopathy and to other various causes (33%). Before implantation, mean ejection fraction was 14% ± 4%, 7 (54%) patients had previous cardiac surgery, 4 (31%) were on mechanical ventilation, and 3 (23%) patients were on dialysis. The mean duration of TAH support was 46 ± 40 days. Three (23%) patients died while on support after a mean of 15 days. Actuarial survival on support was 77% ± 12% at 30 days after implantation. Complications on support included stroke ( n = 1, 8%), acute respiratory distress syndrome requiring prolonged intubation ( n = 5, 38%) and acute renal failure requiring temporary dialysis ( n = 5, 38%). Ten (77%) patients survived to be transplanted after a mean of 52 ± 42 days of support. Actuarial survival rates after transplant were 67% ± 16% at 1 month and 56% ± 17% at 1 year after transplantation. The TAH provides an alternative with low incidence of neurologic events in extremely fragile and complex patients waiting for heart transplantation. Complex and unusual anatomic conditions explained the current use of TAH.

  1. SynCardia Portable Freedom Driver: A Single-Center Experience With 11 Patients.

    PubMed

    Shah, Nilay R; Jaroszewski, Dawn E; Ashfaq, Awais; Schroedl, Lucas A; Staley, Linda L; Pajaro, Octavio E; Kasirajan, Vigneshwar; Arabia, Francisco A

    2015-01-01

    The portable Freedom Drive (SynCardia Inc, Tucson, AZ USA) for total artificial heart (TAH-t) support was approved for an investigational device exemption study in March 2010. We review our center's experience with the portable driver. A retrospective review was conducted of patients who underwent TAH-t implantation and transfer to portable driver from September 2008 to June 2012, with follow-up through December 2012. A total of 30 patients underwent TAH-t implantation during this time period, with 11 patients successfully transferred to the Freedom Driver. Transfer to Freedom Driver after TAH-t implant was a median of 46 days (range, 225-86 days). Ninety-one percent (10) of 11 patients transferred to Freedom Driver were bridged to transplantation. One patient died on support. Five (45.5%) of 11 patients were discharged home and 5 (45.5%) remained in-patient on the portable driver before transplantation. Four patients (80%) successfully discharged home required at least 1 hospital readmission (range, 1-5 admissions per patient). Six patients (55%) transferred to the portable driver required a return to a main driver console. Two patients were temporarily maintained on the main driver then returned to the Freedom Driver for bridge to transplantation. Patients with TAH-t can be considered for transfer to the portable Freedom Driver while awaiting transplantation. Issues that complicated this patient population included inadequate social support, hemodynamic instability, and concurrent morbidities. The potential benefits of the portable driver are currently undergoing assessment. These may include increased mobility and improved quality of life, opportunity for discharge home, and decreased overall medical costs.

  2. Birth, life, and demise of the Andean-syn-collisional Gissar arc: Late Paleozoic tectono-magmatic-metamorphic evolution of the southwestern Tian Shan, Tajikistan

    NASA Astrophysics Data System (ADS)

    Worthington, James R.; Kapp, Paul; Minaev, Vladislav; Chapman, James B.; Mazdab, Frank K.; Ducea, Mihai N.; Oimahmadov, Ilhomjon; Gadoev, Mustafo

    2017-10-01

    The amalgamation of the Central Asian Orogenic Belt in the southwestern Tian Shan in Tajikistan is represented by tectono-magmatic-metamorphic processes that accompanied late Paleozoic ocean closure and collision between the Karakum-Tarim and Kazakh-Kyrgyz terranes. Integrated U-Pb geochronology, thermobarometry, pseudosection modeling, and Hf geochemistry constrain the timing and petro-tectonic nature of these processes. The Gissar batholith and the Garm massif represent an eastward, along-strike increase in paleodepth from upper-batholith ( 21-7 km) to arc-root ( 36-19 km) levels of the Andean-syn-collisional Gissar arc, which developed from 323-288 Ma in two stages: (i) Andean, I-type granitoid magmatism from 323-306 Ma due to northward subduction of the Gissar back-arc ocean basin under the Gissar microcontinent, which was immediately followed by (ii) syn-collisional, I-S-type granitoid magmatism in the Gissar batholith and the Garm massif from 304-288 Ma due to northward subduction/underthrusting of Karakum marginal-continental crust under the Gissar microcontinent. A rapid isotopic pull-up from 288-286 Ma signals the onset of juvenile, alkaline-syenitic, post-collisional magmatism by 280 Ma, which was driven by delamination of the Gissar arclogite root and consequent convective asthenospheric upwelling. Whereas M-HT/LP prograde metamorphism in the Garm massif (650-750°C/6-7 kbar) from 310-288 Ma was associated with subduction-magma inundation and crustal thickening, HT/LP heating and decompression to peak-metamorphic temperatures ( 800-820°C/6-4 kbar) at 288 ± 6 Ma was driven by the transmission of a post-collisional, mantle-derived heat wave through the Garm-massif crust.

  3. Rational design of syn-safencin, a novel linear antimicrobial peptide derived from the circular bacteriocin safencin AS-48.

    PubMed

    Fields, Francisco R; Carothers, Katelyn E; Balsara, Rashna D; Ploplis, Victoria A; Castellino, Francis J; Lee, Shaun W

    2018-06-01

    Bacteriocins hold unprecedented promise as a largely untapped source of antibiotic alternatives in the age of multidrug resistance. Here, we describe the first approach to systematically design variants of a novel AS-48 bacteriocin homologue, which we have termed safencin AS-48, from Bacillus safensis, to gain insights into engineering improved activity of bacteriocins. A library of synthetic peptides in which systematic amino acid substitutions to vary the periodicity and abundance of polar, acidic, aliphatic, and hydrophobic residues were generated for a total of 96 novel peptide variants of a single bacteriocin candidate. Using this method, we identified nine synthetic safencin (syn-safencin) variants with broad and potent antimicrobial activities with minimal inhibitory concentrations (MIC) as low as 250 nM against E. coli, P. aeruginosa, X. axonopodis, and S. pyogenes with minimal cytotoxicity to mammalian cells. It is anticipated that the strategies we have developed will serve as general guides for tuning the specificity of a given natural bacteriocin compound for therapeutic specificity.

  4. Locally extensive meningoencephalitis caused by Miamiensis avidus (syn. Philasterides dicentrarchi) in a zebra shark.

    PubMed

    Li, Wen-Ta; Lo, Chieh; Su, Chen-Yi; Kuo, Hsuan; Lin, Susanne Je-Han; Chang, Hui-Wei; Pang, Victor Fei; Jeng, Chian-Ren

    2017-10-18

    Scuticociliatosis, caused by ciliated protozoa in the subclass Scuticociliatia of the phylum Ciliophora, can cause fatal disease in teleost fish species. However, information on scuticociliatosis in elasmobranchs is still scarce. In this report, we describe a case of locally extensive meningoencephalitis caused by Miamiensis avidus (syn. Philasterides dicentrarchi) in a 2 yr old captive zebra shark Stegostoma fasciatum. Granulocytic meningoencephalitis was observed through histological assessment. Inflammation was confined to the ventral aspect of the brain with a large number of ciliated protozoa, transforming into non-suppurative meningitis in the lateral aspect, and gradually vanished in the dorsal aspect. No histopathological and polymerase chain reaction (PCR) evidence of systemic dissemination of M. avidus was found. PCR targeting the gene coding the small-subunit ribosomal RNA (SSUrRNA) of M. avidus was performed on the brain, liver, and gill tissues, and only brain tissue yielded a positive result. The DNA sequences from amplicons of the protozoal SSUrRNA gene were completely matched to that of M. avidus. The distribution of protozoa in the current case was mainly located in the brain and suggests the possibility of a direct neural invasive pathway of M. avidus through the nasal cavity/ampullary system and/or a unique tissue tropism of M. avidus specific to the brain in zebra sharks. Further investigations on the pathogenesis of M. avidus in elasmobranchs, especially zebra sharks, are needed.

  5. Syn-metamorphic interconnected porosity during blueschist facies reactive fluid fluxes at the slab-mantle interface

    NASA Astrophysics Data System (ADS)

    Konrad-Schmolke, Matthias; Klitscher, Nicolai; Halama, Ralf; Wirth, Richard; Morales, Luiz

    2017-04-01

    At the slab-mantle interface in subdution zones fluids released from the downgoing plate infiltrate into a mechanical mixture of rocks with different chemical compositions, different hydration states and different rheological behaviour resulting in a highly reactive mélange within a steep temperature gradient. Fluid pathways, reaction mechanisms and reaction rates of such fluxes, however, are poorly known, although these parameters are thought to be crucial for several seismic phenomena, such as those commonly referred to as slow earthquakes (e.g., episodic tremor and slip (ETS)). We discovered syn-metamorphic fluid-pathways in the form of interconnected metamorphic porosity in eclogite and blueschist facies mélange rocks from the Franciscan Complex near Jenner, CA. The sampled rocks occur as rigid mafic blocks of different sizes (cm to decametre) in a weak chlorite-serpentine matrix interpreted to be an exhumed slab-mantle interface. Some of these mafic blocks record reactive fluid infiltration that transforms dry eclogite into hydrous blueschist with a sharp reaction front clearly preserved and visible from outcrop- down to µm-scale. We can show that a number of interconnected fluid pathways, such as interconnected metamorphic porosity between reacting omphacite and newly formed sodic amphibole enabled fluid infiltration and interface coupled solution-reprecipitation reactions at blueschist facies conditions. We investigated the different types of fluid pathways with TEM and visualized their interconnectivity with 3D focused ion beam (FIB) sections. The eclogitic parts of the samples preserve porous primary omphacite as a product of amphibole and epidote breakdown during subduction. This primary porosity in omphacite I results from a negative volume change in the solids during amphibole and epidote dehydration. The resulting pores appear as (fluid filled) elongated inclusions the orientations of which are controlled by the omphacite lattice. During

  6. Paléocontraintes et déformations syn- et post-collision Afrique Europe identifiées dans la couverture mésozoïque et cénozoïque du Haut Atlas occidental (Maroc)Syn- and post-collision Africa Europe palaeostresses and deformations identified in the West High-Atlas Mesozoic and Cenozoic cover (Morocco)

    NASA Astrophysics Data System (ADS)

    Amrhar, Mostafa

    Palaeostresses and deformation axis reconstruction related to the intracontinental High-Atlas uplift evidences two shortening phases from Upper Cretaceous to Quaternary. The first compression is oriented N20-30°E and is Maastrichtian to Oligocene age; the second one, oriented N120-160°E, is syn-Mio-Pliocene. Tectonic inversion of the lateral to compressive Jurassic regime is contemporaneous with the beginning of Africa and Europe collision. Rotation of the Mio-Pliocene shortening orientation could be linked to the change of the convergence direction between the Africa and Europe plates. To cite this article: M. Amrhar, C. R. Geoscience 334 (2002) 279-285.

  7. Co-infections of the cestode Echinococcus vogeli and the nematode Calodium hepaticum in the hystricomorphic rodent Agouti paca from a forest reserve in Acre, Brazil.

    PubMed

    Almeida, F; Caldas, R; Corrêa, C; Rodrigues-Silva, R; Siqueira, N; Machado-Silva, J R

    2013-12-01

    The helminth fauna of Agouti paca (Linnaeus, 1766) has seldom been studied. In this paper, we report an unusual mixed infection of Echinococcus vogeli Rausch & Bernstein, 1972 and Calodium hepaticum (syn. Capillaria hepatica Bancroft, 1863) in free-ranging paca from a forested region in Acre (Brazil). Gross morphological examination revealed that paca liver contained multiple spherical to subspherical white or translucent lesions, which were isolated or frequently contiguous and partially covered by Glisson's capsule. Microscopic examination revealed unilocular cystic structures that contained abundant brood capsules in which numerous protoscolices budded from the inner surface. The protoscolices possessed rostellar hooks (33-41 μm in length), a morphological characteristic of the blade and calcareous corpuscles that is consistent with the metacestode E. vogeli. The diagnosis of C. hepaticum infection was based on the morphology and morphometry of the egg-shaped ellipsoids with bipolar plugs (44.8 ± 1.9 μm (length) × 24.4 ± 2.0 μm (width)) and liver histopathology. This finding expands the known range of C. hepaticum hosts in South America and, to the best of our knowledge, it is the first case of a mixed infection of E. vogeli and C. hepaticum. Furthermore, our data provide evidence that wild animal meat may be a source of C. hepaticum infection.

  8. Dips, ramps, and rolls- Evidence for paleotopographic and syn-depositional fault control on the Western Kentucky No. 4 coal bed, tradewater formation (Bolsovian) Illinois Basin

    USGS Publications Warehouse

    Greb, S.F.; Eble, C.F.; Williams, D.A.; Nelson, W.J.

    2001-01-01

    The Western Kentucky No. 4 coal is a high-volatile B to high-volatile C bituminous coal that has been heavily mined along the southern margin of the Western Kentucky Coal Field. The seam has a reputation for rolling floor elevation. Elongate trends of floor depressions are referred to as "dips" and "rolls" by miners. Some are relatively narrow and straight to slightly curvilinear in plan view, with generally symmetric to slightly asymmetric cross-sections. Others are broader and asymmetric in section, with sharp dips on one limb and gradual, ramp-like dips on the other. Some limbs change laterally from gradual dip, to sharp dip, to offset of the coal. Lateral changes in the rate of floor elevation dip are often associated with changes in coal thickness, and in underground mines, changes in floor elevation are sometimes associated with roof falls and haulage problems. In order to test if coal thickness changes within floor depressions were associated with changes in palynology, petrography and coal quality, the coal was sampled at a surface mine across a broad. ramp-like depression that showed down-dip coal thickening. Increment samples of coal from a thick (150 cm), down-ramp and thinner (127 cm), up-ramp position at one surface mine correlate well between sample sites (a distance of 60 m) except for a single increment. The anomalous increment (31 cm) in the lower-middle part of the thick coal bed contained 20% more Lycospora orbicula spores. The rolling floor elevations noted in the study mines are inferred to have been formed as a result of pre-peat paleotopographic depressions, syn-depositional faulting, fault-controlled pre-peat paleotopography, and from compaction beneath post-depositional channels and slumps. Although the association of thick coal with linear trends and inferred faults has been used in other basins to infer syn-depositional faulting, changes in palynology within increment samples of the seam along a structural ramp in this study provide

  9. Syn/anti isomerization of 2,4-dinitrophenylhydrazones in the determination of airborne unsymmetrical aldehydes and ketones using 2,4-dinitrophenylhydrazine derivation.

    PubMed

    Binding, N; Müller, W; Witting, U

    1996-10-01

    Aldehydes and ketones readily react with 2,4-dinitrophenylhydrazine (2,4-DNPH) to form the corresponding hydrazones. This reaction has been frequently used for the quantification of airborne carbonyl compounds. Since unsymmetrical aldehydes and ketones are known to form isomeric 2,4-dinitrophenylhydrazones (syn/ anti-isomers), the influence of isomerization on the practicability and accuracy of the 2,4-DNPH-method using 2,4-dinitrophenylhydrazine-coated solid sorbent samplers has been studied with three ketones (methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK), and methyl isobutyl ketone (MIBK)). With all three ketones the reaction with 2,4-DNPH resulted in mixtures of the isomeric hydrazones which were separated by HPLC and GC and identified by mass spectroscopy and (1)H nuclear magnetic resonance spectroscopy. The isomers show similar chromatographic behaviour in HPLC as well as in GC, thus leading to problems in quantification and interpretation of chromatographic results.

  10. Studies on endoparasites of the black bear (Ursus americanus) in the southeastern United States.

    PubMed

    Crum, J M; Nettles, V F; Davidson, W R

    1978-04-01

    Examination of 53 black bears (Ursus americanus) from six states in the southeastern United States revealed at least 17 species of endoparasites, including Sarcocystis sp., Spirometra mansonoides (spargana), Macracanthorhynchus ingens, Ancylostoma caninum, Arthrocephalus lotoris, Baylisascaris transfuga, Capillaria aerophila, Capillaria putorii, Crenosoma sp., Cyathospirura sp., Dirofilaria immitis, Gnathostoma sp., Gongylonema pulchrum, microfilariae, Molineus barbatus, Physaloptera sp. and Strongyloides sp. Twelve of these represent new host records for black bear, and two are considered to be new species. Data are presented on prevalence, intensity and geographic distribution of each species. Pathologic effects were associated with infections of spargana of S. mansonoides and adults of C. aerophilia.

  11. Genome Sequencing and Analysis of the Biomass-Degrading Fungus Trichoderma reesei (syn. Hypocrea jecorina)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martinez, Antonio D.; Berka, Randy; Henrissat, Bernard

    2008-05-01

    A major thrust of the white biotechnology movement involves the development of enzyme systems which depolymerize biomass to simple sugars which are subsequently converted to sustainable biofuels (e.g., ethanol) and chemical intermediates. The fungus Trichoderma reesei (syn. Hypocrea jecorina) represents a paradigm for the industrial production of highly efficient cellulases and hemicellulases needed for hydrolysis of biomass polysaccharides. Herein we describe intriguing attributes of the T. reeseigenome in relation to the future of fuel biotechnology. The T. reesei genome sequence was derived using a whole genome shotgun approach combined with finishing work to generate an assembly comprising 89 scaffolds totalingmore » 34 Mbp with few gaps. In total, 9,130 gene models were predicted using a combination of ab initio and sequence similarity-based methods and EST data. Considering the industrial utility and effectiveness of its enzymes, the T. reesei genome surprisingly encodes the fewest cellulases and hemicellulases of any fungus having the ability to hydrolyze plant cell wall polysaccharides and whose genome has been sequenced. Many genes encoding carbohydrate active enzymes are distributed non-randomly in groups or clusters that interestingly lie between regions of synteny with other Sordariomycetes. Additionally, the T. reesei genome contains a multitude of genes encoding biosynthetic pathways for secondary metabolites (possible antibacterial and antifungal compounds) which may promote successful competition and survival in the crowded and competitive soil habitat occupied by T. reesei. Our analysis coupled with the availability of genome sequence data provides a roadmap for construction of enhanced T. reesei strains for industrial applications.« less

  12. Natural infection by gastrointestinal and bronchopulmonary nematodes in mouflons (Ovis musimon) and their response to netobimin treatment.

    PubMed

    Meana, A; Luzón-Peña, M; Santiago-Moreno, J; De Bulnes, A; Gómez-Bautista, M

    1996-01-01

    Gastrointestinal and bronchopulmonary nematode infections and the efficacy of netobimin (Hapasil) were analyzed by way of fecal examination in 10 female mouflons (Ovis musimon), in central Spain, February 1993. Before treatment all 10 mouflons had Trichostrongylus axei, Teladorsagia circumcincta and Marshallagia spp.; sic had Nematodirus spp., two had Trichuris sp., one had Capillaria sp., seven had bronchopulmonary Dictyocaulus filaria and 10 mouflons had protostrongylid lungworms (Muellerius capillaris, Protostrongylus rufescens, Cystocaulus ocreatus or Neostrongylus linearis). Netobimin (7.5 mg/kg) was 100% effective against T. axei, T. circumcincta, Marshallagia spp., and D. filaria infections whereas one animal continued eliminating Nematodirus spp. eggs. The drug also was effective against Capillaria spp. but not against Trichuris spp. or protostrongylid infections.

  13. Syn-collisional I-type Esenköy Pluton (Eastern Anatolia-Turkey): An indication for collision between Arabian and Eurasian plates

    NASA Astrophysics Data System (ADS)

    Açlan, Mustafa; Altun, Yusuf

    2018-06-01

    The Esenköy pluton which is situated in the East Anatolian Accretionary Complex (EACC) is represented by I-type, metalumino, calc-alkaline, VAG + syn-COLG, gabbro, diorite, quartz diorite, tonalite and granodiorite type rocks. This paper presents the characteristics of the above granitoids on their major, trace, rare earth elements (REE) and their zircon U-Pb dating. Zircon U-Pb crystallisation ages for gabbro, tonalite and granodiorite are 22.3 ± 0.2 Ma, 21.7 ± 0.2 Ma and 21.8 ± 0.2 Ma respectively. Esenköy granitoids show medium and high-K calc-alkaline character, with six exceptional K-poor sample plot in tholeiitic series field. The Rb/Y-Nb/Y diagram for Esenköy granitoids display subduction zone enrichment trend. The data which obtained from major, trace and REE geochemical characteristics and 206Pb/238U ages indicate that the collision which is take place between Arabian and Eurasian plates along the Bitlis-Zagros suture zone has begun in the Early Miocene (Aquitanian) or before from Early Miocene.

  14. Helminth parasites in the endangered Ethiopian wolf, Canis simensis.

    PubMed

    van Kesteren, F; Piggott, K J; Bengui, T; Kubri, S B; Mastin, A; Sillero-Zubiri, C; Paris, M; Millar, R P; Macdonald, D W; Shiferaw, F; Craig, P S

    2015-07-01

    Ethiopian wolves, Canis simensis, are an endangered carnivore endemic to the Ethiopian highlands. Although previous studies have focused on aspects of Ethiopian wolf biology, including diet, territoriality, reproduction and infectious diseases such as rabies, little is known of their helminth parasites. In the current study, faecal samples were collected from 94 wild Ethiopian wolves in the Bale Mountains of southern Ethiopia, between August 2008 and February 2010, and were screened for the presence of helminth eggs using a semi-quantitative volumetric dilution method with microscopy. We found that 66 of the 94 faecal samples (70.2%) contained eggs from at least one group of helminths, including Capillaria, Toxocara, Trichuris, ancylostomatids, Hymenolepis and taeniids. Eggs of Capillaria sp. were found most commonly, followed by Trichuris sp., ancylostomatid species and Toxocara species. Three samples contained Hymenolepis sp. eggs, which were likely artefacts from ingested prey species. Four samples contained taeniid eggs, one of which was copro-polymerase chain reaction (copro-PCR) and sequence positive for Echinococcus granulosus, suggesting a spillover from a domestic parasite cycle into this wildlife species. Associations between presence/absence of Capillaria, Toxocara and Trichuris eggs were found; and egg burdens of Toxocara and ancylostomatids were found to be associated with geographical location and sampling season.

  15. Helminth infections in faecal samples of Apennine wolf (Canis lupus italicus) and Marsican brown bear (Ursus arctos marsicanus) in two protected national parks of central Italy

    PubMed

    Paoletti, Barbara; Iorio, Raffaella; Traversa, Donato; Di Francesco, Cristina E; Gentile, Leonardo; Angelucci, Simone; Amicucci, Cristina; Bartolini, Roberto; Marangi, Marianna; Di Cesare, Angela

    This article reports the results of a copromicroscopic and molecular investigation carried out on faecal samples of wolves (n=37) and brown bears (n=80) collected in two protected national parks of central Italy (Abruzzo Region). Twenty-three (62.2%) samples from wolves were positive for parasite eggs. Eight (34.78%) samples scored positive for single infections, i.e. E. aerophilus (21.74%), Ancylostoma/Uncinaria (4.34%), Trichuris vulpis (4.34%), T. canis (4.34%). Polyspecific infections were found in 15 samples (65.21%), these being the most frequent association: E. aerophilus and Ancylostoma/Uncinaria. Thirty-seven (46.25%) out of the 80 faecal samples from bears were positive for parasite eggs. Fourteen (37.83%) samples were positive for B. transfuga, and six (16.21%) of them also contained Ancylostoma/Uncinaria, one (2.7%) E. aerophilus and one (2.7%) both E. aerophilus and Ancylostoma/Uncinaria. Of the other samples, 19 (51.35%) were positive for Ancylostoma/Uncinaria, two (5.4%) for E. aerophilus and two (5.4%) for both. Molecular analysis found the roundworm and capillariid eggs found in wolves and bear samples to be Toxocara canis, Baylisascaris transfuga and Eucoleus aerophilus (syn. Capillaria aerophila). Considering the high prevalence of zoonotic intestinal helminths detected in this study, it is important to improve the knowledge and awareness of the general public and park operators regarding the potential health risk associated with infections in wildlife.

  16. The NASA POWER SSE: Deriving the Direct Normal Counterpart from the CERES SYN1deg Hourly Global Horizontal Irradiance during Early 2000 to Near Present

    NASA Astrophysics Data System (ADS)

    Zhang, T.; Stackhouse, P. W., Jr.; Westberg, D. J.

    2017-12-01

    The NASA Prediction of Worldwide Energy Resource (POWER) Surface meteorology and Solar Energy (SSE) provides solar direct normal irradiance (DNI) data as well as a variety of other solar parameters. The currently available DNIs are monthly means on a quasi-equal-area grid system with grid boxes roughly equivalent to 1 degree longitude by 1 degree latitude around the equator from July 1983 to June 2005, and the data were derived from the GEWEX Surface Radiation Budget (SRB) monthly mean global horizontal irradiance (GHI, Release 3) and regression analysis of the Baseline Surface Radiation Network (BSRN) data. To improve the quality of the DNI data and push the temporal coverage of the data to near present, we have applied a modified version of the DIRINDEX global-to-beam model to the GEWEX SRB (Release 3) all-sky and clear-sky 3-hourly GHI data and derived their DNI counterparts for the period from July 1983 to December 2007. The results have been validated against the BSRN data. To further expand the data in time to near present, we are now applying the DIRINDEX model to the Clouds and the Earth's Radiant Energy System (CERES) data. The CERES SYN1deg (Edition 4A) offers hourly all-sky and clear-sky GHIs on a 1 degree longitude by 1 degree latitude grid system from March 2000 to October 2016 as of this writing. Comparisons of the GHIs with their BSRN counterparts show remarkable agreements. Besides the GHIs, the inputs will also include the atmospheric water vapor and surface pressure from the Modern Era Retrospective-Analysis for Research and Applications (MERRA) and the aerosol optical depth from the Max-Planck Institute Climatology (MAC-v1). Based on the performance of the DIRINDEX model with the GEWEX SRB GHI data, we expect at least equally good or even better results. In this paper, we will show the derived hourly, daily, and monthly mean DNIs from the CERES SYN1deg hourly GHIs from March 2000 to October 2016 and how they compare with the BSRN data.

  17. Influence of the position of the methoxy group on the stabilities of the syn and anti conformers of 4-, 5-, and 6-methoxyindole

    NASA Astrophysics Data System (ADS)

    Wilke, Martin; Brand, Christian; Wilke, Josefin; Schmitt, Michael

    2017-07-01

    Even though the two possible rotamers of methoxy-substituted indoles only differ in the orientation of a methoxy group, this slight geometry change can have a strong influence on the stabilities and further molecular properties of the conformers. In the present study, we evaluate the effect of the methyl group position on the presence of different conformers in molecular beam studies for the systems 4-, 5-, and 6-methoxyindole. By using rotationally resolved electronic Stark spectroscopy in combination with high level ab initio calculations the structures of the observable conformers have been assigned and reasons for the absence of the missing conformers discussed. Thereby, we could show that the relative ground state energies and isomerization barriers for both conformers strongly depend on the position of the methoxy group and are the main explanation for the absence of the syn conformers of 4-, and 5-methoxyindole.

  18. Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations

    PubMed Central

    Matthews, Holly; Deakin, Jon; Rajab, May; Idris-Usman, Maryam

    2017-01-01

    The widespread introduction of artemisinin-based combination therapy has contributed to recent reductions in malaria mortality. Combination therapies have a range of advantages, including synergism, toxicity reduction, and delaying the onset of resistance acquisition. Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of effective drugs with distinct target pathways. To fast-track antimalarial drug discovery, we have previously employed drug-repositioning to identify the anti-amoebic drug, emetine dihydrochloride hydrate, as a potential candidate for repositioned use against malaria. Despite its 1000-fold increase in in vitro antimalarial potency (ED50 47 nM) compared with its anti-amoebic potency (ED50 26–32 uM), practical use of the compound has been limited by dose-dependent toxicity (emesis and cardiotoxicity). Identification of a synergistic partner drug would present an opportunity for dose-reduction, thus increasing the therapeutic window. The lack of reliable and standardised methodology to enable the in vitro definition of synergistic potential for antimalarials is a major drawback. Here we use isobologram and combination-index data generated by CalcuSyn software analyses (Biosoft v2.1) to define drug interactivity in an objective, automated manner. The method, based on the median effect principle proposed by Chou and Talalay, was initially validated for antimalarial application using the known synergistic combination (atovaquone-proguanil). The combination was used to further understand the relationship between SYBR Green viability and cytocidal versus cytostatic effects of drugs at higher levels of inhibition. We report here the use of the optimised Chou Talalay method to define synergistic antimalarial drug interactivity between emetine dihydrochloride hydrate and atovaquone. The novel findings present a potential route to harness the nanomolar antimalarial efficacy of this affordable natural product. PMID:28257497

  19. Parasites of wild animals as a potential source of hazard to humans.

    PubMed

    Gałęcki, Remigiusz; Sokół, Rajmund; Koziatek, Sylwia

    2015-01-01

    The decline in wild animal habitats and the uncontrolled growth of their population make these animals come closer to human settlements. The aim of the study was to identify parasitic infections in wild animals in the selected area, and to specify the hazards they create for humans. In more than 66% of the analysed faecal samples from wild boar, hares, roe deer, deer and fallow deer various developmental forms of parasites were found. These included parasites dangerous for humans: Toxocara canis, Capillaria hepatica, Capillaria bovis, Trichuris suis, Trichuris ovis, Trichuris globulosus, Eimeria spp., and Trichostongylus spp. It is necessary to monitor parasitic diseases in wild animals as they can lead to the spread of parasites creating a hazard to humans, pets and livestock.

  20. Base Pair Opening in a Deoxynucleotide Duplex Containing a cis-syn Thymine Cyclobutane Dimer Lesion

    PubMed Central

    Wenke, Belinda B.; Huiting, Leah N.; Frankel, Elisa B.; Lane, Benjamin F.; Núñez, Megan E.

    2014-01-01

    The cis-syn thymine cyclobutane dimer is a DNA photoproduct implicated in skin cancer. We compared the stability of individual base pairs in thymine dimer-containing duplexes to undamaged parent 10-mer duplexes. UV melting thermodynamic measurements, CD spectroscopy, and 2D NOESY NMR spectroscopy confirm that the thymine dimer lesion is locally and moderately destabilizing within an overall B-form duplex conformation. We measured the rates of exchange of individual imino protons by NMR using magnetization transfer from water and determined the equilibrium constant for the opening of each base pair Kop. In the normal duplex Kop decreases from the frayed ends of the duplex toward the center, such that the central TA pair is the most stable with a Kop of 8×10−7. In contrast, base pair opening at the 5’T of the thymine dimer is facile. The 5’T of the dimer has the largest equilibrium constant (Kop =3×10−4) in its duplex, considerably larger than even the frayed penultimate base pairs. Notably, base pairing by the 3’T of the dimer is much more stable than by the 5’T, indicating that the predominant opening mechanism for the thymine dimer lesion is not likely to be flipping out into solution as a single unit. The dimer asymmetrically affects the stability of the duplex in its vicinity, destabilizing base pairing on its 5’ side more than on the 3’ side. The striking differences in base pair opening between parent and dimer duplexes occur independently of the duplex-single strand melting transitions. PMID:24328089

  1. Property study of poly nitro compounds of cis-syn-cis-2, 6-dioxodecahydro-lH, 5H-diimidazo [4, 5-b: 4', 5'-e] pyrazine

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Xu, Zhibin; Xu, Yudong; Xu, Liang; Meng, Zihui

    2017-03-01

    Poly nitro group substituted cis-syn-cis-2, 6-dioxodecahydro-lH, 5H-diimidazo [4, 5-b: 4', 5'-e] pyrazine derivatives are synthesized by modified method and adequately characterized. All compounds have good performance both in density (ρ> 1.85 g/cm3) and high detonation velocity (vD > 8800 m/s, calculated). Some representative compounds, for example, 4 (vD: 9405 ms-1; P: 41.6 GPa) and 5 (vD:9781 ms-1; P: 45.6 GPa) exhibit excellent detonation performances, which are comparable with current energetic compounds such as RDX (vD: 8724 ms-1; P: 35.2 GPa) and HMX (vD:9059 ms-1; P: 39.2 GPa). Considering the sensitivity increasing with the number of nitro group, two componds with tetranitro groups (2 and 3) are worthy of deep research.

  2. Quantitative Trait Locus Analysis for Deep-Sowing Germination Ability in the Maize IBM Syn10 DH Population

    PubMed Central

    Liu, Hongjun; Zhang, Lin; Wang, Jiechen; Li, Changsheng; Zeng, Xing; Xie, Shupeng; Zhang, Yongzhong; Liu, Sisi; Hu, Songlin; Wang, Jianhua; Lee, Michael; Lübberstedt, Thomas; Zhao, Guangwu

    2017-01-01

    Deep-sowing is an effective measure to ensure seeds absorbing water from deep soil layer and emerging normally in arid and semiarid regions. However, existing varieties demonstrate poor germination ability in deep soil layer and some key quantitative trait loci (QTL) or genes related to deep-sowing germination ability remain to be identified and analyzed. In this study, a high-resolution genetic map based on 280 lines of the intermated B73 × Mo17 (IBM) Syn10 doubled haploid (DH) population which comprised 6618 bin markers was used for the QTL analysis of deep-sowing germination related traits. The results showed significant differences in germination related traits under deep-sowing condition (12.5 cm) and standard-germination condition (2 cm) between two parental lines. In total, 8, 11, 13, 15, and 18 QTL for germination rate, seedling length, mesocotyl length, plumule length, and coleoptile length were detected for the two sowing conditions, respectively. These QTL explained 2.51–7.8% of the phenotypic variance with LOD scores ranging from 2.52 to 7.13. Additionally, 32 overlapping QTL formed 11 QTL clusters on all chromosomes except for chromosome 8, indicating the minor effect genes have a pleiotropic role in regulating various traits. Furthermore, we identified six candidate genes related to deep-sowing germination ability, which were co-located in the cluster regions. The results provide a basis for molecular marker assisted breeding and functional study in deep-sowing germination ability of maize. PMID:28588594

  3. Quantitative Trait Locus Analysis for Deep-Sowing Germination Ability in the Maize IBM Syn10 DH Population.

    PubMed

    Liu, Hongjun; Zhang, Lin; Wang, Jiechen; Li, Changsheng; Zeng, Xing; Xie, Shupeng; Zhang, Yongzhong; Liu, Sisi; Hu, Songlin; Wang, Jianhua; Lee, Michael; Lübberstedt, Thomas; Zhao, Guangwu

    2017-01-01

    Deep-sowing is an effective measure to ensure seeds absorbing water from deep soil layer and emerging normally in arid and semiarid regions. However, existing varieties demonstrate poor germination ability in deep soil layer and some key quantitative trait loci (QTL) or genes related to deep-sowing germination ability remain to be identified and analyzed. In this study, a high-resolution genetic map based on 280 lines of the intermated B73 × Mo17 (IBM) Syn10 doubled haploid (DH) population which comprised 6618 bin markers was used for the QTL analysis of deep-sowing germination related traits. The results showed significant differences in germination related traits under deep-sowing condition (12.5 cm) and standard-germination condition (2 cm) between two parental lines. In total, 8, 11, 13, 15, and 18 QTL for germination rate, seedling length, mesocotyl length, plumule length, and coleoptile length were detected for the two sowing conditions, respectively. These QTL explained 2.51-7.8% of the phenotypic variance with LOD scores ranging from 2.52 to 7.13. Additionally, 32 overlapping QTL formed 11 QTL clusters on all chromosomes except for chromosome 8, indicating the minor effect genes have a pleiotropic role in regulating various traits. Furthermore, we identified six candidate genes related to deep-sowing germination ability, which were co-located in the cluster regions. The results provide a basis for molecular marker assisted breeding and functional study in deep-sowing germination ability of maize.

  4. The Afar-Red Sea-Gulf of Aden volcanic margins system : early syn-rift segmentation and tectono-magmatic evolution

    NASA Astrophysics Data System (ADS)

    Stab, Martin; Leroy, Sylvie; Bellahsen, Nicolas; Pik, Raphaël; Ayalew, Dereje; Yirgu, Gezahegn; Khanbari, Khaled

    2017-04-01

    The Afro-Arabian rift system is characterized by complex interactions between magmatism and rifting, leading to long-term segmentation of the associated continental margins. However, past studies focused on specific rift segments and no attempt has yet been made to reconcile them into a single comprehensive geodynamic model. To address this, we present interpretations of seismic profiles offshore the Eritrea-Yemeni margins in the southern Red Sea and the Yemeni margin in the Gulf of Aden and reassess the regional geodynamic evolution including the new tectonic evolution of the Central Afar Magmatic margin. We point out the role of two major transform zones in structuring the volcanism and faulting of the Red Sea-Afar-Aden margins. We show that those transform zones not only control the present-day rift organization, but were also active since the onset of rifting in Oligocene times. Early syn-rift transform zones control the emplacement and the development of seaward-dipping-reflector wedges immediately after the Continental Flood basalts (30 Ma), and are closely associated with mantle plume melts in the course of the segment extension. The margins segmentation thus appears to reflect the underlying mantle dynamics and thermal anomaly, which have directly influenced the style of rifting (wide vs. narrow rift), in controlling the development of preferential lithospheric thinning and massive transfer of magmas in the crust.

  5. Helminth parasites of the digestive tract of the oystercatcher, Haematopus ostralegus, in the Wadden Sea, The Netherlands

    NASA Astrophysics Data System (ADS)

    Borgsteede, F. H. M.; Van den Broek, E.; Swennen, C.

    The digestive tracts of 90 oystercatchers (equal numbers of males and females and of juveniles, subadults and adults) wintering in the Dutch Wadden Sea were examined for helminth parasites. The nematodes Capillaria sp. (36.7%) and Streptocara crassicauda (7.8%) were found in the stomach. Unidentified cestodes (76.7%) and the trematodes Psilostomum brevicolle (42.2%), Notocotylus sp. (81.1%), and unidentified gymnophallids (100%) were found in the intestine and caeca. Two birds were infected with Gymnophallidae only, while all other birds contained additional helminth species. Compared with subadult and adult birds, the juveniles had significantly more infections with Capillaria sp. and cestodes. Moreover, the juveniles were infected with a greater variety of species. No further relation was found between the presence of helminths or worm numbers and age groups or sexes of birds.

  6. The Mt. Ochi melange (South Evvia Island, Greece): a case study for HP metamorphism and syn-convergent exhumation.

    NASA Astrophysics Data System (ADS)

    Moustaka, Eleni; Soukis, Konstantinos; Huet, Benjamin; Lozios, Stylianos; Magganas, Andreas

    2014-05-01

    The Attic-Cycladic complex (central Aegean Sea, Greece) experienced profound extension since at least the Oligo-Miocene boundary during which the previously thickened crust was reworked by a series of detachments forming the NE directed North Cycladic Detachment System (NCDS) and the SSW directed West Cycladic Detachment System (WCDS). South Evvia Island is located at the northwestern part of the Attic Cycladic complex linking the highly thinned and polymetamorphosed central part of the complex with mainland Greece. Furthermore, greenschists-facies retrograde metamorphism has only partially overprinted the HP mineral assemblages. Consequently, it is an ideal area to study tectonic processes associated with subduction, HP metamorphism and subsequent exhumation from eclogitic depths to the surface. Geological mapping in 1:2:000 scale revealed that the tectonostratigraphy of Mt. Ochi includes three distinct units all metamorphosed in HP conditions followed by greenschist facies overprint. These units are from top to bottom a) the Ochi Unit, a thick metavolcanosedimentary sequence with some intensely folded cipoline marble intercalations and isolated occurrences of metabasic rocks b) the ophiolitic mélange (metagabbros, metawherlites, peridotites, metabasites within a metasedimentary+serpentinite matrix) and c) the lowermost Styra Unit, a cipoline marble-dominated unit with thin mica schists and rare quartzitic layers often boudinaged. The thrust fault that was responsible for the juxtaposition of these three units acted in an early stage during HP metamorphism and it was isoclinally folded and sheared by the following syn-metamorphic deformation events. Detailed structural study in meso- and microscopic scale combined with petrological and geochemical analyses of the Mt Ochi rocks led to the distinction of at least three syn-metamorphic and two post-metamorphic deformation episodes that affected all units. The oldest structure identified is a relic foliation formed

  7. Recombinant expression and characterization of an acid-, alkali- and salt-tolerant β-1,3-1,4-glucanase from Paenibacillus sp. S09.

    PubMed

    Cheng, Rui; Xu, Linxiang; Wang, Shiming; Wang, Yang; Zhang, Jianfa

    2014-04-01

    A new β-1,3-1,4-glucanase gene (PlicA) was cloned from Paenibacillus sp. S09. The ORF contained 717 bp coding for a 238 amino acid protein. PlicA, expressed in Escherichia coli and purified by Ni(2+)-affinity chromatography, had optimum activity at 55 °C and pH 6.2. The specific activity toward barley β-glucan reached 7,055 U/mg. K m and V max values with barley β-glucan were 3.7 mg/ml and 3.3 × 10(3) μmol/min mg, respectively. The enzyme exhibited acid- and alkali-tolerance with more than 80 % activity remaining after incubation for 4 h at pH 3.5-12. PlicA was salt-tolerant (>90 % activity retained in 4 M NaCl at 25 °C for 24 h) and salt-activated: activity rising 1.5-fold in 0.5 M NaCl. The thermostability was improved by NaCl and CaCl2. This is the first report of an acid-, alkali- and salt-tolerant bacterial β-1,3-1,4-glucanase with high catalytic efficiency.

  8. Geochemical signature variation of pre-, syn-, and post-shearing intrusives within the Najd Fault System of western Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Hassan, M.; Abu-Alam, T. S.; Hauzenberger, C.; Stüwe, K.

    2016-10-01

    Late Precambrian intrusive rocks in the Arabian-Nubian Shield emplaced within and around the Najd Fault System of Saudi Arabia feature a great compositional diversity and a variety of degrees of deformation (i.e. pre-shearing deformed, sheared mylonitized, and post-shearing undeformed) that allows placing them into a relative time order. It is shown here that the degree of deformation is related to compositional variations where early, usually pre-shearing deformed rocks are of dioritic, tonalitic to granodioritic, and later, mainly post-shearing undeformed rocks are mostly of granitic composition. Correlation of the geochemical signature and time of emplacement is interpreted in terms of changes in the source region of the produced melts due to the change of the stress regime during the tectonic evolution of the Arabian-Nubian Shield. The magma of the pre-shearing rocks has tholeiitic and calc-alkaline affinity indicating island arc or continental arc affinity. In contrast, the syn- and post-shearing rocks are mainly potassium rich peraluminous granites which are typically associated with post-orogenic uplift and collapse. This variation in geochemical signature is interpreted to reflect the change of the tectonic regime from a compressional volcanic arc nature to extensional within-plate setting of the Arabian-Nubian Shield. Within the context of published geochronological data, this change is likely to have occurred around 605-580 Ma.

  9. Environmental determinants of the spatial distribution of Angiostrongylus vasorum, Crenosoma vulpis and Eucoleus aerophilus in Hungary.

    PubMed

    Tolnai, Z; Széll, Z; Sréter, T

    2015-01-30

    Angiostrongylus vasorum, Crenosoma vulpis and Eucoleus aerophilus (syn. Capillaria aerophila) are the most important lungworm species infecting wild and domesticated canids in Europe. To investigate the spatial distribution of these parasites and the factors influencing their circulation in the fox populations, 937 red foxes (Vulpes vulpes) were tested for lungworm infection in Hungary. The prevalence of A. vasorum, C. vulpis and E. aerophilus infection was high (17.9, 24.6 and 61.7%). The distribution pattern of infection in foxes and the relationship of this pattern with landscape and climate was analyzed by geographic information system. Based on the analysis, the annual precipitation was the major determinant of the spatial distribution of A. vasorum and C. vulpis and E. aerophilus. Nevertheless, the mean annual temperature also influenced the distribution of A. vasorum and E. aerophilus. The positive relationship with annual precipitation and the negative relationship with mean annual temperature can be attributed to the sensitivity of larvae, eggs and intermediate hosts (snails and slugs) of lungworms for desiccation. Based on the highly clumped distribution of A. vasorum and C. vulpis, the indirect life cycle (larvae, slugs and snails) of these parasites seems to be particularly sensitive for environmental effects. The distribution of E. aerophilus was considerably less clumped indicating a lower sensitivity of the direct life cycle (eggs) of this parasite for environmental factors. Based on these results, lungworm infections in canids including dogs can be expected mainly in relatively wet and cool areas. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. [Results of parasitological examinations of faecal samples from horses, ruminants, pigs, dogs, cats, hedgehogs and rabbits between 1998 and 2002].

    PubMed

    Epe, C; Coati, N; Schnieder, T

    2004-06-01

    The results of coproscopical examinations in horses, ruminants, pigs, dogs, cats, hedgehogs and rabbits between 1998 and 2002 are presented. In 4399 samples from horses 37.4% stages of strongylids, 1.4% anoplocephalids, 1.3% Strongyloides westeri, 0.9% Parascaris equorum, 0.04% Oxyuris equi, 0.04% Eimeria sp. and 0.04% Fasciola hepatica were found. In 998 samples of cattle 22.1% stages of strongylids, 11.2% of Eimeria spp., 3.5% of cryptosporidium, 2.9% of Moniezia spp., 1.3% of Trichuris spp., 0.7% of Dictyocaulus sp., 0.6% of Fasciola hepatica, 0.6% of Strongyloides sp., 0.5% of Nematodirus spp. and 0.4% of Capillaria sp. could be detected. In 524 samples of sheep 60.7% eggs of strongylids, 43.1% oozysts of Eimeria spp., 11.1% stages of Nematodirus spp., 9.5% of Moniezia spp., 7.8% of Trichuris spp., 6.7% of Strongyloides sp., 1.7% of Fasciola hepatica, 1% of Capillaria spp., 0.4% of protostrongylidae, 0.2% of Skrjabinema sp. and 0.2% of Dictyocaulus sp. were found. 33.9% of the 118 samples of goats that were examined were positive for oocysts of Eimeria spp., 30.5% for eggs of strongylids, 6.8% for Nematodirus spp., 4.2% for Trichuris spp., 3.4% for Moniezia spp., 0.8 for protostrongylids and 0.8% for Strongyloides sp. 5.7% of 1427 samples of pigs contained stages of strongylids, 1.5% of Ascaris suum, 0.4% of Isospora, 0.3% of Eimeria spp., 0.3% of Trichuris sp., 0.1% of Giardia sp., 0.1% of cryptosproidium as well as 0.1% of metastrongylids. In 1281 of the samples of dogs 2.3% Giardia sp., 2.3% Isospora sp., 2.2% Toxocara canis, 1.4% ancylostomids, 0.8% taeniids, 0.6% larvae of Crenosoma sp., 0.2% Capillaria sp, 0.2% Trichuris vulpis and 0.2% Hammondia-like oocysts were found. In 441 samples of cats 10.7% stages of Isospora sp., 3.9% eggs of Toxocara cati, 1.6% of ancylostomids, 1.4% of taeniids, 1.1% of Giardia sp., 0.7% of Toxoplasma-like oocysts, 0.7% of Aelurostrongylus abstrusus, 0.5% of Toxascaris leonina and 0.2% of Capillaria spp. were found

  11. QTL Mapping of Low-Temperature Germination Ability in the Maize IBM Syn4 RIL Population

    PubMed Central

    Hu, Shuaidong; Lübberstedt, Thomas; Zhao, Guangwu; Lee, Michael

    2016-01-01

    Low temperature is the primary factor to affect maize sowing in early spring. It is, therefore, vital for maize breeding programs to improve tolerance to low temperatures at seed germination stage. However, little is known about maize QTL involved in low-temperature germination ability. 243 lines of the intermated B73×Mo17 (IBM) Syn4 recombinant inbred line (RIL) population was used for QTL analysis of low-temperature germination ability. There were significant differences in germination-related traits under both conditions of low temperature (12°C/16h, 18°C/8h) and optimum temperature (28°C/24h) between the parental lines. Only three QTL were identified for controlling optimum-temperature germination rate. Six QTL controlling low-temperature germination rate were detected on chromosome 4, 5, 6, 7 and 9, and contribution rate of single QTL explained between 3.39%~11.29%. In addition, six QTL controlling low-temperature primary root length were detected in chromosome 4, 5, 6, and 9, and the contribution rate of single QTL explained between 3.96%~8.41%. Four pairs of QTL were located at the same chromosome position and together controlled germination rate and primary root length under low temperature condition. The nearest markers apart from the corresponding QTL (only 0.01 cM) were umc1303 (265.1 cM) on chromosome 4, umc1 (246.4 cM) on chromosome 5, umc62 (459.1 cM) on chromosome 6, bnl14.28a (477.4 cM) on chromosome 9, respectively. A total of 3155 candidate genes were extracted from nine separate intervals based on the Maize Genetics and Genomics Database (http://www.maizegdb.org). Five candidate genes were selected for analysis as candidates putatively affecting seed germination and seedling growth at low temperature. The results provided a basis for further fine mapping, molecular marker assisted breeding and functional study of cold-tolerance at the stage of seed germination in maize. PMID:27031623

  12. Segmental allotetraploidy and allelic interactions in buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.) as revealed by genome mapping.

    PubMed

    Jessup, R W; Burson, B L; Burow, O; Wang, Y W; Chang, C; Li, Z; Paterson, A H; Hussey, M A

    2003-04-01

    Linkage analyses increasingly complement cytological and traditional plant breeding techniques by providing valuable information regarding genome organization and transmission genetics of complex polyploid species. This study reports a genome map of buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.). Maternal and paternal maps were constructed with restriction fragment length polymorphisms (RFLPs) segregating in 87 F1 progeny from an intraspecific cross between two heterozygous genotypes. A survey of 862 heterologous cDNAs and gDNAs from across the Poaceae, as well as 443 buffelgrass cDNAs, yielded 100 and 360 polymorphic probes, respectively. The maternal map included 322 RFLPs, 47 linkage groups, and 3464 cM, whereas the paternal map contained 245 RFLPs, 42 linkage groups, and 2757 cM. Approximately 70 to 80% of the buffelgrass genome was covered, and the average marker spacing was 10.8 and 11.3 cM on the respective maps. Preferential pairing was indicated between many linkage groups, which supports cytological reports that buffelgrass is a segmental allotetraploid. More preferential pairing (disomy) was found in the maternal than paternal parent across linkage groups (55 vs. 38%) and loci (48 vs. 15%). Comparison of interval lengths in 15 allelic bridges indicated significantly less meiotic recombination in paternal gametes. Allelic interactions were detected in four regions of the maternal map and were absent in the paternal map.

  13. 3D imaging of vesicles in hyaloclastic fragments - clues to syn-eruptive shear conditions

    NASA Astrophysics Data System (ADS)

    Helo, C.; Flaws, A.; Hess, K.; Franz, A.; Clague, D. A.; Dingwell, D. B.

    2011-12-01

    3D imaging of stretched vesicles in hyaloclastic fragments has been used to investigate the shear environment of mild pyroclastic eruptions at mid-ocean ridges. X-ray computed tomography offers an attractive non-invasive method to investigate geomaterials at a high resolution for the geometry of the different phases. In this study, we have imaged vesicles within two types of basaltic glass fragments. Stretched, ellipsoid-shaped vesicles in thin limu o Pele and tubular vesicles in a pumiceous fragment. Both types originate from pyroclastic activity on Axial Seamount, Juan de Fuca ridge. Rapid quenching of the glass has prevented extensive bubble relaxation and information about syn-eruptive shear and differential stress conditions is stored, as the dimensions of a stretched bubble directly relates to the extent and mode of shearing. The X-ray tomography data was processed using a set of codes based on edge detection and ellipsoid fitting to acquire quantitative information on the shape of the stretched vesicles. Preliminary results demonstrate, that the geometry of the stretched vesicles, e.g., the elongation of the vesicle with respect to the calculated undeformed radius, is in accordance with simple shear scenarios. Stored differential stress ranges from 5 kPa to 90 kPa with shear rates between 3.2x102 s-1 and 5.7x3 s-1 within a single limu o Pele fragment. This range may be explained by either variable time available for relaxation as the cooling front proceeds through the fragment, complex interplay in space and time between fragmentation and quenching, bubble clusters mutually inhibiting each others extend of deformation, or any combination of these. Bubble relaxation time scales are less then 0.005 s providing constraints on the timeframe for cooling to the glass transition. Qualitative analyses of the tube pumice indicates that the tubular structures grow in length by coalescence of vertically aligned ellipsoid-shaped vesicles, and in width by coalescence of

  14. Mapping lacustrine syn-rift reservoir distribution using spectral attributes: A case study of the Pematang Brownshale Central Sumatra Basin

    NASA Astrophysics Data System (ADS)

    Haris, A.; Yustiawan, R.; Riyanto, A.; Ramadian, R.

    2017-07-01

    Pematang Brownshale is the lake sediment, which is proven as the main source rock in Malacca Strait Area. So far Brownshale is only considered as source rock, but the well data show intercalated sand layers encountered within the Pematang Brownshale, where several downhole tests proved this series as a potential hydrocarbon reservoir. Pematang formation is a syn-rift sequent deposited in Malacca Strait following the opening of central Sumatra basin during a late cretaceous to early Oligocene, which is proven as potential source rock and reservoir. The aim of the study is to identify the distribution of sandstone reservoir in Pematang Brownshale using spectral attributes. These works were carried out by integrating log data analysis and frequency maps extracted from spectral attributes Continuous Wavelet Transform (CWT). All these data are used to delineate reservoir distribution in Pematang Brownshale. Based on CWT analysis the anomalies are only visible on the frequency of I5 and I0 Hz maps, which are categorized as low frequencies. Low-frequency shadow anomaly is commonly used as an indication of the presence of hydrocarbons. The distribution of these anomalies is covering an area of approximately 3840.66 acres or equal to I554.25 sq. km, where the low-frequency pattern is interpreted as a deltaic lacustrine feature. By considering the Pematang Brown Shale of Malacca Strait area as a potential reservoir, it would open new play to another basin that has similar characteristics.

  15. Battling the un-dead: the status of the Diptera genus-group names originally proposed in Johann Wilhelm Meigen's 1800 pamphlet.

    PubMed

    Evenhuis, Neal L; Pape, Thomas

    2017-06-08

    The work of Meigen 1800 was suppressed by the ICZN Commission in 1963 for the purposes of zoological nomenclature. The work as such is still to be treated as having been published and it remains available as a source of published descriptions and illustrations. Therefore, while the names in Meigen (1800) are deemed unavailable, a subsequent usage of any of the names may be considered a novel proposal. We review the first post-Meigen 1800 occurrence of each name, its first date of availability and authorship, and determine status and synonymy.        Designations of type species are given for the following genus-group names: Coryneta Hendel, 1908 [Hybotidae]; Cyanea Hendel, 1908 [Hippoboscidae].        Acting as First Reviser, we select the following as the correct original spelling from multiple original spellings: Calirrhoe Hendel, 1908.        New synonymies are proposed for the following: Ablabesmyia Johannsen, 1905 under Pelopia Latreille, 1802, n. syn. [Limoniidae]; Amasia Meigen in Hendel, 1908 under Penthetria Meigen, 1803, n. syn. [Bibionidae]; Amphinome Meigen in Hendel, 1908 under Limonia Meigen, 1803, n. syn. [Limoniidae]; Antiopa Meigen in Hendel, 1908 under Chrysotoxum Meigen, 1803, n. syn. [Syrphidae]; Apivora Meigen in Hendel, 1908 under Volucella Geoffroy, 1762, n. syn. [Syrphidae]; Atalanta Meigen in Hendel, 1908 under Clinocera Meigen, 1803, n. syn. [Empididae]; Calirrhoe Meigen & Hendel in Hendel, 1908 under Prosena Le Peletier & Audinet-Serville, 1828, n. syn. [Tachinidae]; Chrysozona Hendel, 1903 under Haematopota Meigen, 1803, n. syn. [Tabanidae]; Cinxia Meigen in Hendel, 1908 under Sericomyia Meigen, 1803, n. syn. [Syrphidae]; Cleona Meigen in Hendel 1908 under Callomyia Meigen, 1804, n. syn. [Platypezidae]; Clythia Hendel, 1903 under Platypeza Meigen, 1803, n. syn. [Platypezidae]; Coryneta Meigen in Hendel, 1908 under Tachydromia Meigen, 1803, n. syn. [Hybotidae]; Crocuta Bezzi, 1907 under Siphona Meigen, 1803, n. syn

  16. Autism-related behavioral abnormalities in synapsin knockout mice.

    PubMed

    Greco, Barbara; Managò, Francesca; Tucci, Valter; Kao, Hung-Teh; Valtorta, Flavia; Benfenati, Fabio

    2013-08-15

    Several synaptic genes predisposing to autism-spectrum disorder (ASD) have been identified. Nonsense and missense mutations in the SYN1 gene encoding for Synapsin I have been identified in families segregating for idiopathic epilepsy and ASD and genetic mapping analyses have identified variations in the SYN2 gene as significantly contributing to epilepsy predisposition. Synapsins (Syn I/II/III) are a multigene family of synaptic vesicle-associated phosphoproteins playing multiple roles in synaptic development, transmission and plasticity. Lack of SynI and/or SynII triggers a strong epileptic phenotype in mice associated with mild cognitive impairments that are also present in the non-epileptic SynIII(-/-) mice. SynII(-/-) and SynIII(-/-) mice also display schizophrenia-like traits, suggesting that Syns could be involved in the regulation of social behavior. Here, we studied social interaction and novelty, social recognition and social dominance, social transmission of food preference and social memory in groups of male SynI(-/-), SynII(-/-) and SynIII(-/-) mice before and after the appearance of the epileptic phenotype and compared their performances with control mice. We found that deletion of Syn isoforms widely impairs social behaviors and repetitive behaviors, resulting in ASD-related phenotypes. SynI or SynIII deletion altered social behavior, whereas SynII deletion extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming. Social impairments of SynI(-/-) and SynII(-/-) mice were evident also before the onset of seizures. The results demonstrate an involvement of Syns in generation of the behavioral traits of ASD and identify Syn knockout mice as a useful experimental model of ASD and epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Nature, geochemistry and petrogenesis of the syn-tectonic Amspoort suite (Pan-African Boundary Igneous Complex, Kaoko Belt, NW Namibia)

    NASA Astrophysics Data System (ADS)

    Janousek, Vojtech; Konopasek, Jiri; Ulrich, Stanislav

    2010-05-01

    Crucial information on the Neoproterozoic-Cambrian amalgamation of Western Gondwana is provided by studies of the large Pan-African collisional belt in central-northern Namibia. This so-called Damara Orogen (Miller, 1983) can be subdivided into two branches, the SW-NE trending Damara Belt and a roughly perpendicular, NNW-SSE trending Kaoko Belt further north. The Kaoko Belt consists of two principal crustal units. The easterly part has a Congo Craton affinity (a basement built mostly by ≥ 1.5 Ga granitic gneisses with Neoproterozoic metasedimentary cover), whereas the westerly Coastal Terrane consists of Neoproterozoic (c.850-650 Ma) metapsammites and minor metabasic bodies; no exposures of the basement were found. The at least 180 km long, NNW-SSE trending suture between both units was intruded by numerous syn-tectonic magmatic bodies with ages spanning the interval 580-550 Ma (Seth et al., 1998; Kröner et al., 2004) designated as the Boundary Igneous Complex by Konopásek et al. (2008). The most typical representatives of this syn-collision igneous association are c.550 Ma old K-feldspar-phyric, Bt ± Cam granites-granodiorites of the Amspoort suite, with minor Cpx gabbro and rare two-pyroxene dolerite bodies. The petrological character, whole-rock geochemistry and Sr-Nd isotopic signatures of the scarce Opx-Cpx-Bt dolerites indicate an origin from a CHUR-like mantle-derived melts (87Sr/86Sr550 ~ 0.7045, ɛNd550 ~ 0) modified by extensive (?Ol-) Cpx fractionation. The rest of the suite is interpreted as a product of a high-temperature anatexis of a heterogeneous lower crust, built mainly by immature metapsammites - rich in arc-derived detritus - with minor metabasite and intermediate metaigneous bodies. The most likely source appears to be the anatectic Coastal Terrane gneisses. Yet, partial melting of the so far little constrained Congo Craton cover, if formed by immature and youthful detritus unrelated to the basement, cannot be discounted. In any case, the

  18. Impact of pre- and/or syn-tectonic salt layers in the hangingwall geometry of a kinked-planar extensional fault: insights from analogue modelling and comparison with the Parentis basin (bay of Biscay)

    NASA Astrophysics Data System (ADS)

    Ferrer, O.; Vendeville, B. C.; Roca, E.

    2012-04-01

    Using sandbox analogue modelling we determine the role played by a pre-kinematic or a syn-kinematic viscous salt layer during rollover folding of the hangingwall of a normal fault with a variable kinked-planar geometry, as well as understand the origin and the mechanisms that control the formation, kinematic evolution and geometry of salt structures developed in the hangingwall of this fault. The experiments we conducted consisted of nine models made of dry quartz-sand (35μm average grain size) simulating brittle rocks and a viscous silicone polymer (SMG 36 from Dow Corning) simulating salt in nature. The models were constructed between two end walls, one of which was fixed, whereas the other was moved by a motor-driven worm screw. The fixed wall was part of the rigid footwall of the model's master border fault. This fault was simulated using three different wood block configurations, which was overlain by a flexible (but not stretchable) sheet that was attached to the mobile endwall of the model. We applied three different infill hangingwall configurations to each fault geometry: (1) without silicone (sand only), (2) sand overlain by a pre-kinematic silicone layer deposited above the entire hanginwall, and (3) sand partly overlain by a syn-kinematic silicone layer that overlain only parts of the hangingwall. All models were subjected to a 14 cm of basement extension in a direction orthogonal to that of the border fault. Results show that the presence of a viscous layer (silicone) clearly controls the deformation pattern of the hangingwall. Thus, regardless of the silicone layer's geometry (either pre- or syn-extensional) or the geometry of the extensional fault, the silicone layer acts as a very efficient detachment level separating two different structural styles in each unit. In particular, the silicone layer acts as an extensional ductile shear zone inhibiting upward propagation of normal faults and/or shears bands from the sub-silicone layers. Whereas the

  19. α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells

    PubMed Central

    Hansen, Christian; Angot, Elodie; Bergström, Ann-Louise; Steiner, Jennifer A.; Pieri, Laura; Paul, Gesine; Outeiro, Tiago F.; Melki, Ronald; Kallunki, Pekka; Fog, Karina; Li, Jia-Yi; Brundin, Patrik

    2011-01-01

    Post-mortem analyses of brains from patients with Parkinson disease who received fetal mesencephalic transplants show that α-synuclein–containing (α-syn–containing) Lewy bodies gradually appear in grafted neurons. Here, we explored whether intercellular transfer of α-syn from host to graft, followed by seeding of α-syn aggregation in recipient neurons, can contribute to this phenomenon. We assessed α-syn cell-to-cell transfer using microscopy, flow cytometry, and high-content screening in several coculture model systems. Coculturing cells engineered to express either GFP– or DsRed-tagged α-syn resulted in a gradual increase in double-labeled cells. Importantly, α-syn–GFP derived from 1 neuroblastoma cell line localized to red fluorescent aggregates in other cells expressing DsRed–α-syn, suggesting a seeding effect of transmitted α-syn. Extracellular α-syn was taken up by cells through endocytosis and interacted with intracellular α-syn. Next, following intracortical injection of recombinant α-syn in rats, we found neuronal uptake was attenuated by coinjection of an endocytosis inhibitor. Finally, we demonstrated in vivo transfer of α-syn between host cells and grafted dopaminergic neurons in mice overexpressing human α-syn. In summary, intercellularly transferred α-syn interacts with cytoplasmic α-syn and can propagate α-syn pathology. These results suggest that α-syn propagation is a key element in the progression of Parkinson disease pathology. PMID:21245577

  20. Characterization of antibodies that selectively detect alpha-synuclein in pathological inclusions.

    PubMed

    Waxman, Elisa A; Duda, John E; Giasson, Benoit I

    2008-07-01

    Sensitive detection of alpha-synuclein (alpha-syn) pathology is important in the diagnosis of disorders like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy and in providing better insights into the etiology of these diseases. Several monoclonal antibodies that selectively react with aggregated alpha-syn in pathological inclusions and reveal extensive and underappreciated alpha-syn pathology in the brains of diseased patients were previously reported by Duda et al. (Ann Neurol 52:205-210, 2002). We sought to characterize the specificity of some of these antibodies (Syn 505, Syn 506 and Syn 514); using C-terminal and N-terminal truncations of alpha-syn, all three antibodies were determined to require N-terminal epitopes that minimally comprise amino acids 2-4, but possibly extend to amino acid 12 of alpha-syn. The selectivity of these antibodies was further assessed using biochemical analysis of human brains and reactivity to altered recombinant alpha-syn proteins with duplication variants of amino acids 1-12. In addition, by expressing wild-type or a double mutant (E46K/A53T) of alpha-syn in cultured cells and by comparing their immunoreactivities to another antibody (SNL-4), which has a similar primary epitope, it was determined that Syn 505, Syn 506 and Syn 514 recognize conformational variants of alpha-syn that is enhanced by the presence of the double mutations. These studies indicate that antibodies Syn 505, Syn 506 and Syn 514 preferentially recognize N-terminal epitopes in complex conformations, consistent with the dramatic conformational change associated with the polymerization of alpha-synuclein into amyloid fibrils that form pathological inclusions.

  1. Comparative Analysis of the Conformation, Aggregation, Interaction, and Fibril Morphologies of Human α-, β-, and γ-Synuclein Proteins.

    PubMed

    Jain, Manish Kumar; Singh, Priyanka; Roy, Sneha; Bhat, Rajiv

    2018-06-13

    The human synuclein (syn) family is comprised of α-, β-, and γ-syn proteins. α-syn has the highest propensity for aggregation, and its aggregated forms accumulate in Lewy bodies (LB) and Lewy neurites, which are involved in Parkinson's disease (PD). β- and γ-syn are absent in LB, and their exact role is still enigmatic. β-syn does not form aggregates under physiological conditions (pH 7.4), while γ-syn is associated with neural and non-neural diseases like breast cancer. Because of their similar regional distribution in the brain, natively unfolded structure, and high degree of sequence homology, studying the effect of the environment on their conformation, interactions, fibrillation, and fibril morphologies has become important. Our studies show that high temperatures, low pH values, and high concentrations increase the rate of fibrillation of α- and γ-syn, while β-syn forms fibrils only at low pH. Fibril morphologies are strongly dependent on the immediate environment of the proteins. The high molar ratio of β-syn inhibits the fibrillation in α- and γ-syn. However, preformed seed fibrils of β- and γ-syn do not affect fibrillation of α-syn. Surface plasmon resonance data show that interactions between α- and β-syn, β- and γ-syn, and α- and γ-syn are weak to moderate in nature and can be physiologically significant in counteracting several adverse conditions in the cells that trigger their aggregation. These studies could be helpful in understanding collective human synuclein behavior in various protein environments and in the modulation of the homeostasis between β-syn and healthy versus corrupt α- and γ-syn that can potentially affect PD pathology.

  2. High-density lipoprotein-like particle formation of Synuclein variants.

    PubMed

    Eichmann, Cédric; Kumari, Pratibha; Riek, Roland

    2017-01-01

    α-Synuclein (α-Syn) is an intrinsically disordered protein in solution whose fibrillar aggregates are the hallmark of Parkinson's disease (PD). Although the specific function of α-Syn is still unclear, its high structural plasticity is key for the interactions of α-Syn with biological membranes. Recently, it has been observed that α-Syn is able to form high-density lipoprotein-like (HDL-like) particles that are reminiscent of self-assembling phospholipid bilayer nanodiscs. Here, we extended our preparation method for the production of α-Syn lipoprotein particles to the β- and γ-Syn variants, and the PD-related familial α-Syn mutants. We show that all human Syns can form stable and homogeneous populations of HDL-like particles with distinct morphologies. Our results characterize the impact of the individual Syns on the formation capacity of these particles and indicate that Syn HDL-like particles are neither causing toxicity nor a toxicity-related loss of α-Syn in PD. © 2016 Federation of European Biochemical Societies.

  3. Effects of Serine 129 Phosphorylation on α-Synuclein Aggregation, Membrane Association, and Internalization*

    PubMed Central

    Samuel, Filsy; Flavin, William P.; Iqbal, Sobia; Pacelli, Consiglia; Sri Renganathan, Sri Dushyaanthan; Trudeau, Louis-Eric; Campbell, Edward M.; Fraser, Paul E.; Tandon, Anurag

    2016-01-01

    Although trace levels of phosphorylated α-synuclein (α-syn) are detectable in normal brains, nearly all α-syn accumulated within Lewy bodies in Parkinson disease brains is phosphorylated on serine 129 (Ser-129). The role of the phosphoserine residue and its effects on α-syn structure, function, and intracellular accumulation are poorly understood. Here, co-expression of α-syn and polo-like kinase 2 (PLK2), a kinase that targets Ser-129, was used to generate phosphorylated α-syn for biophysical and biological characterization. Misfolding and fibril formation of phosphorylated α-syn isoforms were detected earlier, although the fibrils remained phosphatase- and protease-sensitive. Membrane binding of α-syn monomers was differentially affected by phosphorylation depending on the Parkinson disease-linked mutation. WT α-syn binding to presynaptic membranes was not affected by phosphorylation, whereas A30P α-syn binding was greatly increased, and A53T α-syn was slightly lower, implicating distal effects of the carboxyl- on amino-terminal membrane binding. Endocytic vesicle-mediated internalization of pre-formed fibrils into non-neuronal cells and dopaminergic neurons matched the efficacy of α-syn membrane binding. Finally, the disruption of internalized vesicle membranes was enhanced by the phosphorylated α-syn isoforms, a potential means for misfolded extracellular or lumenal α-syn to access cytosolic α-syn. Our results suggest that the threshold for vesicle permeabilization is evident even at low levels of α-syn internalization and are relevant to therapeutic strategies to reduce intercellular propagation of α-syn misfolding. PMID:26719332

  4. Deformation and thermal histories of ordinary chondrites: Evidence for post-deformation annealing and syn-metamorphic shock

    NASA Astrophysics Data System (ADS)

    Ruzicka, Alex; Hugo, Richard; Hutson, Melinda

    2015-08-01

    We show that olivine microstructures in seven metamorphosed ordinary chondrites of different groups studied with optical and transmission electron microscopy can be used to evaluate the post-deformation cooling setting of the meteorites, and to discriminate between collisions affecting cold and warm parent bodies. The L6 chondrites Park (shock stage S1), Bruderheim (S4), Leedey (S4), and Morrow County (S5) were affected by variable shock deformation followed by relatively rapid cooling, and probably cooled as fragments liberated by impact in near-surface settings. In contrast, Kernouvé (H6 S1), Portales Valley (H6/7 S1), and MIL 99301 (LL6 S1) appear to have cooled slowly after shock, probably by deep burial in warm materials. In these chondrites, post-deformation annealing lowered apparent optical strain levels in olivine. Additionally, Kernouvé, Morrow County, Park, MIL 99301, and possibly Portales Valley, show evidence for having been deformed at an elevated temperature (⩾800-1000 °C). The high temperatures for Morrow County can be explained by dynamic heating during intense shock, but Kernouvé, Park, and MIL 99301 were probably shocked while the H, L and LL parent bodies were warm, during early, endogenically-driven thermal metamorphism. Thus, whereas the S4 and S5 chondrites experienced purely shock-induced heating and cooling, all the S1 chondrites examined show evidence for static heating consistent with either syn-metamorphic shock (Kernouvé, MIL 99301, Park), post-deformation burial in warm materials (Kernouvé, MIL 99301, Portales Valley), or both. The results show the pitfalls in relying on optical shock classification alone to infer an absence of shock and to construct cooling stratigraphy models for parent bodies. Moreover, they provide support for the idea that "secondary" metamorphic and "tertiary" shock processes overlapped in time shortly after the accretion of chondritic planetesimals, and that impacts into warm asteroidal bodies were

  5. 21 CFR 558.55 - Amprolium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... obsignata) Feed according to subtable in item (i) Penicillin 2.4 to 50 Replacement chickens; development of active immunity to coccidiosis; growth promotion and feed efficiency As procaine penicillin. Feed... worms (Capillaria obsignata) Feed according to subtable in item (i) Penicillin 2.4 to 50 Broiler...

  6. Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits.

    PubMed

    Larson, Megan E; Greimel, Susan J; Amar, Fatou; LaCroix, Michael; Boyle, Gabriel; Sherman, Mathew A; Schley, Hallie; Miel, Camille; Schneider, Julie A; Kayed, Rakez; Benfenati, Fabio; Lee, Michael K; Bennett, David A; Lesné, Sylvain E

    2017-06-06

    Mounting evidence indicates that soluble oligomeric forms of amyloid proteins linked to neurodegenerative disorders, such as amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major deleterious species for neuronal function in these diseases. Here, we found an abnormal accumulation of oligomeric αSyn species in AD brains by custom ELISA, size-exclusion chromatography, and nondenaturing/denaturing immunoblotting techniques. Importantly, the abundance of αSyn oligomers in human brain tissue correlated with cognitive impairment and reductions in synapsin expression. By overexpressing WT human αSyn in an AD mouse model, we artificially enhanced αSyn oligomerization. These bigenic mice displayed exacerbated Aβ-induced cognitive deficits and a selective decrease in synapsins. Following isolation of various soluble αSyn assemblies from transgenic mice, we found that in vitro delivery of exogenous oligomeric αSyn but not monomeric αSyn was causing a lowering in synapsin-I/II protein abundance. For a particular αSyn oligomer, these changes were either dependent or independent on endogenous αSyn expression. Finally, at a molecular level, the expression of synapsin genes SYN1 and SYN2 was down-regulated in vivo and in vitro by αSyn oligomers, which decreased two transcription factors, cAMP response element binding and Nurr1, controlling synapsin gene promoter activity. Overall, our results demonstrate that endogenous αSyn oligomers can impair memory by selectively lowering synapsin expression.

  7. Kinematics of syn- and post-exhumational shear zones at Lago di Cignana (Western Alps, Italy): constraints on the exhumation of Zermatt-Saas (ultra)high-pressure rocks and deformation along the Combin Fault and Dent Blanche Basal Thrust

    NASA Astrophysics Data System (ADS)

    Kirst, Frederik; Leiss, Bernd

    2017-01-01

    Kinematic analyses of shear zones at Lago di Cignana in the Italian Western Alps were used to constrain the structural evolution of units from the Piemont-Ligurian oceanic realm (Zermatt-Saas and Combin zones) and the Adriatic continental margin (Dent Blanche nappe) during Palaeogene syn- and post-exhumational deformation. Exhumation of Zermatt-Saas (U)HP rocks to approximately lower crustal levels at ca. 39 Ma occurred during normal-sense top-(S)E shearing under epidote-amphibolite-facies conditions. Juxtaposition with the overlying Combin zone along the Combin Fault at mid-crustal levels occurred during greenschist-facies normal-sense top-SE shearing at ca. 38 Ma. The scarcity of top-SE kinematic indicators in the hanging wall of the Combin Fault probably resulted from strain localization along the uppermost Zermatt-Saas zone and obliteration by subsequent deformation. A phase of dominant pure shear deformation around 35 Ma affected units in the direct footwall and hanging wall of the Combin Fault. It is interpreted to reflect NW-SE crustal elongation during updoming of the nappe stack as a result of underthrusting of European continental margin units and the onset of continental collision. This phase was partly accompanied and followed by ductile bulk top-NW shearing, especially at higher structural levels, which transitioned into semi-ductile to brittle normal-sense top-NW deformation due to Vanzone phase folding from ca. 32 Ma onwards. Our structural observations suggest that syn-exhumational deformation is partly preserved within units and shear zones exposed at Lago di Cignana but also that the Combin Fault and Dent Blanche Basal Thrust experienced significant post-exhumational deformation reworking and overprinting earlier structures.

  8. Anserobilharzia gen. n. (Digenea, Schistosomatidae) and redescription of A. brantae (Farr & Blankemeyer, 1956) comb. n. (syn. Trichobilharzia brantae), a parasite of geese (Anseriformes).

    PubMed

    Brant, Sara V; Jouet, Damien; Ferte, Hubert; Loker, Eric S

    2013-01-01

    A new genus, Anserobilharzia, is proposed to accommodate Anserobilharzia brantae n. comb. (syn. Trichobilharzia bran- tae Farr & Blankemeyer, 1956), a species of avian schistosome thus far found exclusively in anserini geese (Anser, Branta, Chen) from Europe and North America, and Gyraulus snails. Recent collections and subsequent molecular analyses showed that A. brantae was distinct from Allobilharzia and Trichobilharzia and grouped basal to Trichobilharzia. Using nuclear 28S, ITS and mitochondrial cox1 as genetic yardsticks, samples of A. brantae from North America and Europe were each other's closest relative and distinct from Allobilharzia and Trichobilharzia. Anserobilharzia brantae was also distinct when compared morphologically with other species of closely related avian schistosomes. The following descrip- tion is based on males, females, eggs, and cercariae. The new genus is characterized by a) ovoid egg (72-145µm x 44- 89 µm) with spine, b) male with > 500 testes and caecal reunion anteriad to seminal vesicle, c) cercariae with 5+1 flame cells, and d) intermediate hosts are planorbid snails. The only confirmed species of snail host is Gyraulus parvus in North America. Based on presented data, we propose a new genus and new combination for A. brantae justified by morpholog- ical, host use, and molecular characteristics.

  9. Differential effects of immunotherapy with antibodies targeting α-synuclein oligomers and fibrils in a transgenic model of synucleinopathy.

    PubMed

    El-Agnaf, Omar; Overk, Cassia; Rockenstein, Edward; Mante, Michael; Florio, Jazmin; Adame, Anthony; Vaikath, Nishant; Majbour, Nour; Lee, Seung-Jae; Kim, Changyoun; Masliah, Eliezer; Rissman, Robert A

    2017-08-01

    Disorders with progressive accumulation of α-synuclein (α-syn) are a common cause of dementia and parkinsonism in the aging population. Accumulation and propagation of α-syn play a role in the pathogenesis of these disorders. Previous studies have shown that immunization with antibodies that recognize C-terminus of α-syn reduces the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy. These studies employed antibodies that recognize epitopes within monomeric and aggregated α-syn that were generated through active immunization or administered via passive immunization. However, it is possible that more specific effects might be achieved with antibodies recognizing selective species of the α-syn aggregates. In this respect we recently developed antibodies that differentially recognized various oligomers (Syn-O1, -O2, and -O4) and fibrilar (Syn-F1 and -F2) forms of α-syn. For this purpose wild-type α-syn transgenic (line 61) mice were immunized with these 5 different antibodies and neuropathologically and biochemically analyzed to determine which was most effective at reducing α-syn accumulation and related deficits. We found that Syn-O1, -O4 and -F1 antibodies were most effective at reducing accumulation of α-syn oligomers in multiple brain regions and at preventing neurodegeneration. Together this study supports the notion that selective antibodies against α-syn might be suitable for development new treatments for synucleinopathies such as PD and DLB. Published by Elsevier Inc.

  10. Differential effects of immunotherapy with antibodies targeting α-synuclein oligomers and fibrils in a transgenic model of synucleinopathy

    PubMed Central

    El-Agnaf, Omar; Overk, Cassia; Rockenstein, Edward; Mante, Michael; Florio, Jazmin; Adame, Anthony; Vaikath, Nishant; Majbour, Nour; Lee, Seung-Jae; Kim, Changyoun; Masliah, Eliezer; Rissman, Robert A.

    2018-01-01

    Disorders with progressive accumulation of α-synuclein (α-syn) are a common cause of dementia and parkinsonism in the aging population. Accumulation and propagation of α-syn play a role in the pathogenesis of these disorders. Previous studies have shown that immunization with antibodies that recognize C-terminus of α-syn reduces the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy. These studies employed antibodies that recognize epitopes within monomeric and aggregated α-syn that were generated through active immunization or administered via passive immunization. However, it is possible that more specific effects might be achieved with antibodies recognizing selective species of the α-syn aggregates. In this respect we recently developed antibodies that differentially recognized various oligomers (Syn-O1, -O2, and -O4) and fibrilar (Syn-F1 and -F2) forms of α-syn. For this purpose wild-type α-syn transgenic (line 61) mice were immunized with these 5 different antibodies and neuropathologically and biochemically analyzed to determine which was most effective at reducing α-syn accumulation and related deficits. We found that Syn-O1, -O4 and -F1 antibodies were most effective at reducing accumulation of α-syn oligomers in multiple brain regions and at preventing neurodegeneration. Together this study supports the notion that selective antibodies against α-syn might be suitable for development new treatments for synucleinopathies such as PD and DLB. PMID:28476636

  11. Helminth Fauna in Captive European Gray Wolves (Canis lupus lupus) in Germany.

    PubMed

    Bindke, Johanna Daniela; Springer, Andrea; Böer, Michael; Strube, Christina

    2017-01-01

    Captive as well as free-ranging wolves, which are currently recolonizing Germany, may harbor a variety of gastrointestinal parasites. This study investigated endoparasites in captive European gray wolves ( Canis lupus lupus ) using coproscopical methods. Fecal samples were collected monthly between October 2012 and November 2013 from 18 wolf enclosures in 14 German zoological gardens, representing 72 individual wolves. In total, 1,041 fecal samples including 26 bulk samples were analyzed by the sedimentation and flotation method. The most frequently detected egg morphotypes included five nematodes [Ancylostomatidae ( Ancylostoma or Uncinaria spp.), Toxocara canis, Toxascaris leonina, Trichuris vulpis , and Capillaria / Eucoleus spp.], one cestode (Taeniidae) and one trematode ( Alaria alata ). 44.76% of all samples were positive for at least one of these egg morphotypes. Overall, Ancylostomatidae showed the highest frequency (30.84% of all samples), followed by Capillaria/Eucoleus spp. (19.88%), Toxocara canis (5.19%), taeniids (3.75%), Trichuris vulpis and Alaria alata (3.65% each), and Toxascaris leonina (1.25%). As fecal samples were collected from the environment and could not be assigned to individual wolves, sample results were combined per zoo and month. General linear mixed models were employed to analyze the effect of season and management factors on the occurrence of Ancylostomatidae, Capillaria/Eucoleus spp., Toxocara canis and taeniids. No statistically significant effect of season was found, whereas anthelmintic treatment negatively affected Ancylostomatidae egg excretion. Detected parasites and their prevalences are comparable to previous studies on wolf parasitism conducted elsewhere in Europe. As many of the most prevalent helminths are of zoonotic importance, routine anthelmintic treatment of captive wolves should be recommended.

  12. Reducing C-Terminal-Truncated Alpha-Synuclein by Immunotherapy Attenuates Neurodegeneration and Propagation in Parkinson's Disease-Like Models

    PubMed Central

    Games, Dora; Valera, Elvira; Spencer, Brian; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Patrick, Christina; Ubhi, Kiren; Nuber, Silke; Sacayon, Patricia; Zago, Wagner; Seubert, Peter; Barbour, Robin; Schenk, Dale

    2014-01-01

    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders of the aging population, characterized by progressive and abnormal accumulation of α-synuclein (α-syn). Recent studies have shown that C-terminus (CT) truncation and propagation of α-syn play a role in the pathogenesis of PD/DLB. Therefore, we explored the effect of passive immunization against the CT of α-syn in the mThy1-α-syn transgenic (tg) mouse model, which resembles the striato-nigral and motor deficits of PD. Mice were immunized with the new monoclonal antibodies 1H7, 5C1, or 5D12, all directed against the CT of α-syn. CT α-syn antibodies attenuated synaptic and axonal pathology, reduced the accumulation of CT-truncated α-syn (CT-α-syn) in axons, rescued the loss of tyrosine hydroxylase fibers in striatum, and improved motor and memory deficits. Among them, 1H7 and 5C1 were most effective at decreasing levels of CT-α-syn and higher-molecular-weight aggregates. Furthermore, in vitro studies showed that preincubation of recombinant α-syn with 1H7 and 5C1 prevented CT cleavage of α-syn. In a cell-based system, CT antibodies reduced cell-to-cell propagation of full-length α-syn, but not of the CT-α-syn that lacked the 118–126 aa recognition site needed for antibody binding. Furthermore, the results obtained after lentiviral expression of α-syn suggest that antibodies might be blocking the extracellular truncation of α-syn by calpain-1. Together, these results demonstrate that antibodies against the CT of α-syn reduce levels of CT-truncated fragments of the protein and its propagation, thus ameliorating PD-like pathology and improving behavioral and motor functions in a mouse model of this disease. PMID:25009275

  13. Anti-α-synuclein immunotherapy reduces α-synuclein propagation in the axon and degeneration in a combined viral vector and transgenic model of synucleinopathy.

    PubMed

    Spencer, Brian; Valera, Elvira; Rockenstein, Edward; Overk, Cassia; Mante, Michael; Adame, Anthony; Zago, Wagner; Seubert, Peter; Barbour, Robin; Schenk, Dale; Games, Dora; Rissman, Robert A; Masliah, Eliezer

    2017-01-13

    Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models. Here, we assessed the effect of passive immunization against α-syn in a new mouse model of axonal transport and accumulation of α-syn. For these purpose, non-transgenic, α-syn knock-out and mThy1-α-syn tg (line 61) mice received unilateral intra-cerebral injections with a lentiviral (LV)-α-syn vector construct followed by systemic administration of the monoclonal antibody 1H7 (recognizes amino acids 91-99) or control IgG for 3 months. Cerebral α-syn accumulation and axonopathy was assessed by immunohistochemistry and effects on behavior were assessed by Morris water maze. Unilateral LV-α-syn injection resulted in axonal propagation of α-syn in the contra-lateral site with subsequent behavioral deficits and axonal degeneration. Passive immunization with 1H7 antibody reduced the axonal accumulation of α-syn in the contra-lateral side and ameliorated the behavioral deficits. Together this study supports the notion that immunotherapy might improve the deficits in models of synucleinopathy by reducing the axonal propagation and accumulation of α-syn. This represents a potential new mode of action through which α-syn immunization might work.

  14. Magma emplacement mechanisms and syn-magmatic deformation - a new approach to the Knaben area in Vest Agder, Norway

    NASA Astrophysics Data System (ADS)

    Stormoen, Martin Austin; Slagstad, Trond; Henderson, Iain

    2014-05-01

    The Knaben area, known for its molybdenite mining, defines a N-S striking (~30 degrees dip towards the east) belt, consisting of porphyry granite with a varying density of amphibolite and varieties of deformed granite, lying within the Sirdal Magmatic Belt, is important for understanding the emplacement- and deformation mechanisms of the batholith. Detailed geological mapping combined with geochronology, geochemistry, and structural geology will be the focus areas. Last autumn's fieldwork indicated that several of the formerly mapped enclaves of amphibolite and deformed granite are more coherent then previously indicated, and some have been followed for a few kilometres. Several varieties of granite make up the area, mainly a dominating red porphyry granite, and a grey molybdenite-bearing finer grained granite. Structural investigations revealed consistent "top to the west" compressional kinematics on mappable shear zone networks often displaying west-directed duplex geometries. The Knaben area could possibly comprise a boundary between two individual plutons in the Sirdal Magmatic Belt, or a zone with remaining host rock. Geochronology of the eastern and western plutons will be done. Currently, largely different paleomagnetic vectors of the eastern and western porphyry granites indicate that they are separate plutons. Exploring how the emplacement- and deformation mechanisms have acted and are related, will be one of the main objectives. If the deformed granite is host rock, or syn- to post-magmatic deformed porphyry granite has been one of the major questions. A better understanding of the formation of the Knaben area, also regarding the emplacement of molybdenite, will prove useful for understanding the regional batholith, and possibly the possibility for molybdenite to occur elsewhere. The Sirdal Magmatic Belt, and also Knaben, seem to be of great value for studying magmatic processes.

  15. Axonopathy in an α-Synuclein Transgenic Model of Lewy Body Disease Is Associated with Extensive Accumulation of C-Terminal–Truncated α-Synuclein

    PubMed Central

    Games, Dora; Seubert, Peter; Rockenstein, Edward; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Ettle, Benjamin; Ghassemiam, Majid; Barbour, Robin; Schenk, Dale; Nuber, Silke; Masliah, Eliezer

    2014-01-01

    Progressive accumulation of α-synuclein (α-syn) in limbic and striatonigral systems is associated with the neurodegenerative processes in dementia with Lewy bodies (DLB) and Parkinson’s disease (PD). The murine Thy-1 (mThy1)-α-syn transgenic (tg) model recapitulates aspects of degenerative processes associated with α-syn accumulation in these disorders. Given that axonal and synaptic pathologies are important features of DLB and PD, we sought to investigate the extent and characteristics of these alterations in mThy1-α-syn tg mice and to determine the contribution of α-syn c-terminally cleaved at amino acid 122 (CT α-syn) to these abnormalities. We generated a novel polyclonal antibody (SYN105) against the c-terminally truncated sequence (amino acids 121 to 123) of α-syn (CT α-syn) and performed immunocytochemical and ultrastructural analyses in mThy1-α-syn tg mice. We found abundant clusters of dystrophic neurites in layers 2 to 3 of the neocortex, the stratum lacunosum, the dentate gyrus, and cornu ammonis 3 of the hippocampus, striatum, thalamus, midbrain, and pons. Dystrophic neurites displayed intense immunoreactivity detected with the SYN105 antibody. Double-labeling studies with antibodies to phosphorylated neurofilaments confirmed the axonal location of full-length and CT α-syn. α-Syn immunoreactive dystrophic neurites contained numerous electrodense laminated structures. These results show that neuritic dystrophy is a prominent pathologic feature of the mThy1-α-syn tg model and suggest that CT α-syn might play an important role in the process of axonal damage in these mice as well as in DLB and PD. PMID:23313024

  16. Chemoenzymatic synthesis of new 2,4-syn-functionalized (S)-glutamate analogues and structure-activity relationship studies at ionotropic glutamate receptors and excitatory amino acid transporters.

    PubMed

    Assaf, Zeinab; Larsen, Anja P; Venskutonytė, Raminta; Han, Liwei; Abrahamsen, Bjarke; Nielsen, Birgitte; Gajhede, Michael; Kastrup, Jette S; Jensen, Anders A; Pickering, Darryl S; Frydenvang, Karla; Gefflaut, Thierry; Bunch, Lennart

    2013-02-28

    In the mammalian central nervous system, (S)-glutamate (Glu) is released from the presynaptic neuron where it activates a plethora of pre- and postsynaptic Glu receptors. The fast acting ionotropic Glu receptors (iGluRs) are ligand gated ion channels and are believed to be involved in a vast number of neurological functions such as memory and learning, synaptic plasticity, and motor function. The synthesis of 14 enantiopure 2,4-syn-Glu analogues 2b-p is accessed by a short and efficient chemoenzymatic approach starting from readily available cyclohexanone 3. Pharmacological characterization at the iGluRs and EAAT1-3 subtypes revealed analogue 2i as a selective GluK1 ligand with low nanomolar affinity. Two X-ray crystal structures of the key analogue 2i in the ligand-binding domain (LBD) of GluA2 and GluK3 were determined. Partial domain closure was seen in the GluA2-LBD complex with 2i comparable to that induced by kainate. In contrast, full domain closure was observed in the GluK3-LBD complex with 2i, similar to that of GluK3-LBD with glutamate bound.

  17. Fibril growth and seeding capacity play key roles in α-synuclein-mediated apoptotic cell death

    PubMed Central

    Mahul-Mellier, A-L; Vercruysse, F; Maco, B; Ait-Bouziad, N; De Roo, M; Muller, D; Lashuel, H A

    2015-01-01

    The role of extracellular α-synuclein (α-syn) in the initiation and the spreading of neurodegeneration in Parkinson's disease (PD) has been studied extensively over the past 10 years. However, the nature of the α-syn toxic species and the molecular mechanisms by which they may contribute to neuronal cell loss remain controversial. In this study, we show that fully characterized recombinant monomeric, fibrillar or stabilized forms of oligomeric α-syn do not trigger significant cell death when added individually to neuroblastoma cell lines. However, a mixture of preformed fibrils (PFFs) with monomeric α-syn becomes toxic under conditions that promote their growth and amyloid formation. In hippocampal primary neurons and ex vivo hippocampal slice cultures, α-syn PFFs are capable of inducing a moderate toxicity over time that is greatly exacerbated upon promoting fibril growth by addition of monomeric α-syn. The causal relationship between α-syn aggregation and cellular toxicity was further investigated by assessing the effect of inhibiting fibrillization on α-syn-induced cell death. Remarkably, our data show that blocking fibril growth by treatment with known pharmacological inhibitor of α-syn fibrillization (Tolcapone) or replacing monomeric α-syn by monomeric β-synuclein in α-syn mixture composition prevent α-syn-induced toxicity in both neuroblastoma cell lines and hippocampal primary neurons. We demonstrate that exogenously added α-syn fibrils bind to the plasma membrane and serve as nucleation sites for the formation of α-syn fibrils and promote the accumulation and internalization of these aggregates that in turn activate both the extrinsic and intrinsic apoptotic cell death pathways in our cellular models. Our results support the hypothesis that ongoing aggregation and fibrillization of extracellular α-syn play central roles in α-syn extracellular toxicity, and suggest that inhibiting fibril growth and seeding capacity constitute a viable

  18. Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

    PubMed

    Toschi-Dias, Edgar; Trombetta, Ivani C; da Silva, Valdo José Dias; Maki-Nunes, Cristiane; Alves, Maria Janieire N N; Angelo, Luciana F; Cepeda, Felipe X; Martinez, Daniel G; Negrão, Carlos Eduardo; Rondon, Maria Urbana P B

    2013-03-01

    Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.

  19. Some helminth parasites of the American bald eagle

    USGS Publications Warehouse

    Kocan, A.A.; Locke, L.N.

    1974-01-01

    Bald eagles (Haliaeetus leucocephalus) found dead or moribund in the United States and Canada and submitted to Patuxent Wildlife Research Center were examined for helminth parasites. Nine genera of helminths were reported which include new host records for Clinostomum complanatum, Neogogatea pandionis, Centrorhynchus sp., Serratospiculum amaculata, Capillaria contorta, and Habronema americanum.

  20. Antiapoptotic property of human alpha-synuclein in neuronal cell lines is associated with the inhibition of caspase-3 but not caspase-9 activity.

    PubMed

    Li, Wenxue; Lee, Michael K

    2005-06-01

    Abnormalities of alpha-synuclein (alpha-Syn) are mechanistically linked to Parkinson's disease (PD) and other alpha-synucleinopathies. To gain additional insights into the relationships between alpha-Syn expression and cell death, we examined the effects of expressing human alpha-Syn (Hualpha-Syn) variants on the cellular vulnerability to apoptotic stimuli. We show that the expression of wild-type (WT) and A30P mutant, but not A53T mutant, Hualpha-Syn leads to the protection of neuronal cell lines from apoptosis but not necrosis. Significantly, Hualpha-Syn did not protect non-neuronal cell lines from apoptosis. We also show that A53T mutant is a loss of function in regards to the antiapoptotic property since the expression of WT Hualpha-Syn with an excess of A53T mutant Hualpha-Syn leads to protection of the cells from apoptosis. The antiapoptotic property is specific to human alpha-Syn as neither beta-Syn nor mouse alpha-Syn protected cells from apoptosis, and the carboxy-terminal 20 amino acids are required for the antiapoptotic property. Analyses of capase-3 and caspase-9 activation reveal that the antiapoptotic property of Hualpha-Syn in neuronal cell lines is associated with the attenuation of caspase-3 activity without affecting the caspase-9 activity or the levels of cleaved, active caspase-3. We conclude that Hualpha-Syn modulates the activity of cleaved caspase-3 product in neuronal cell lines.

  1. Axonopathy in an α-synuclein transgenic model of Lewy body disease is associated with extensive accumulation of C-terminal-truncated α-synuclein.

    PubMed

    Games, Dora; Seubert, Peter; Rockenstein, Edward; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Ettle, Benjamin; Ghassemiam, Majid; Barbour, Robin; Schenk, Dale; Nuber, Silke; Masliah, Eliezer

    2013-03-01

    Progressive accumulation of α-synuclein (α-syn) in limbic and striatonigral systems is associated with the neurodegenerative processes in dementia with Lewy bodies (DLB) and Parkinson's disease (PD). The murine Thy-1 (mThy1)-α-syn transgenic (tg) model recapitulates aspects of degenerative processes associated with α-syn accumulation in these disorders. Given that axonal and synaptic pathologies are important features of DLB and PD, we sought to investigate the extent and characteristics of these alterations in mThy1-α-syn tg mice and to determine the contribution of α-syn c-terminally cleaved at amino acid 122 (CT α-syn) to these abnormalities. We generated a novel polyclonal antibody (SYN105) against the c-terminally truncated sequence (amino acids 121 to 123) of α-syn (CT α-syn) and performed immunocytochemical and ultrastructural analyses in mThy1-α-syn tg mice. We found abundant clusters of dystrophic neurites in layers 2 to 3 of the neocortex, the stratum lacunosum, the dentate gyrus, and cornu ammonis 3 of the hippocampus, striatum, thalamus, midbrain, and pons. Dystrophic neurites displayed intense immunoreactivity detected with the SYN105 antibody. Double-labeling studies with antibodies to phosphorylated neurofilaments confirmed the axonal location of full-length and CT α-syn. α-Syn immunoreactive dystrophic neurites contained numerous electrodense laminated structures. These results show that neuritic dystrophy is a prominent pathologic feature of the mThy1-α-syn tg model and suggest that CT α-syn might play an important role in the process of axonal damage in these mice as well as in DLB and PD. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. A New Method for Quantitative Immunoblotting of Endogenous α-Synuclein

    PubMed Central

    Newman, Andrew J.; Selkoe, Dennis; Dettmer, Ulf

    2013-01-01

    β-Sheet-rich aggregates of α-synuclein (αSyn) are the hallmark neuropathology of Parkinson’s disease and related synucleinopathies, whereas the principal native structure of αSyn in healthy cells - unfolded monomer or α-helically folded oligomer - is under debate. Our recent crosslinking analysis of αSyn in intact cells showed that a large portion of endogenous αSyn can be trapped as oligomers, most notably as apparent tetramers. One challenge in such studies is accurately quantifying αSyn Western blot signals among samples, as crosslinked αSyn trends toward increased immunoreactivity. Here, we analyzed this phenomenon in detail and found that treatment with the reducible amine-reactive crosslinker DSP strongly increased αSyn immunoreactivity even after cleavage with the reducing agent β-mercaptoethanol. The effect was observed with all αSyn antibodies tested and in all sample types from human brain homogenates to untransfected neuroblastoma cells, permitting easy detection of endogenous αSyn in the latter, which had long been considered impossible. Coomassie staining of blots before and after several hours of washing revealed complete retention of αSyn after DSP/β-mercaptoethanol treatment, in contrast to a marked loss of αSyn without this treatment. The treatment also enhanced immunodetection of the homologs β- and γ-synuclein and of histones, another group of small, lysine-rich proteins. We conclude that by neutralizing positive charges and increasing protein hydrophobicity, amine crosslinker treatment promotes adhesion of αSyn to blotting membranes. These data help explain the recent report of fixing αSyn blots with paraformaldehyde after transfer, which we find produces similar but weaker effects. DSP/β-mercaptoethanol treatment of Western blots should be particularly useful to quantify low-abundance αSyn forms such as extracellular and post-translationally modified αSyn and splice variants. PMID:24278419

  3. Lewy Body-like α-Synuclein Aggregates Resist Degradation and Impair Macroautophagy*♦

    PubMed Central

    Tanik, Selcuk A.; Schultheiss, Christine E.; Volpicelli-Daley, Laura A.; Brunden, Kurt R.; Lee, Virginia M. Y.

    2013-01-01

    Cytoplasmic α-synuclein (α-syn) aggregates, referred to as Lewy bodies, are pathological hallmarks of a number of neurodegenerative diseases, most notably Parkinson disease. Activation of macroautophagy is suggested to facilitate degradation of certain proteinaceous inclusions, but it is unclear if this pathway is capable of degrading α-syn aggregates. Here, we examined this issue by utilizing cellular models in which intracellular Lewy body-like α-syn inclusions accumulate after internalization of pre-formed α-syn fibrils into α-syn-expressing HEK293 cells or cultured primary neurons. We demonstrate that α-syn inclusions cannot be effectively degraded, even though they co-localize with essential components of both the autophagic and proteasomal protein degradation pathways. The α-syn aggregates persist even after soluble α-syn levels have been substantially reduced, suggesting that once formed, the α-syn inclusions are refractory to clearance. Importantly, we also find that α-syn aggregates impair overall macroautophagy by reducing autophagosome clearance, which may contribute to the increased cell death that is observed in aggregate-bearing cells. PMID:23532841

  4. Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson's disease-like models.

    PubMed

    Games, Dora; Valera, Elvira; Spencer, Brian; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Patrick, Christina; Ubhi, Kiren; Nuber, Silke; Sacayon, Patricia; Zago, Wagner; Seubert, Peter; Barbour, Robin; Schenk, Dale; Masliah, Eliezer

    2014-07-09

    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders of the aging population, characterized by progressive and abnormal accumulation of α-synuclein (α-syn). Recent studies have shown that C-terminus (CT) truncation and propagation of α-syn play a role in the pathogenesis of PD/DLB. Therefore, we explored the effect of passive immunization against the CT of α-syn in the mThy1-α-syn transgenic (tg) mouse model, which resembles the striato-nigral and motor deficits of PD. Mice were immunized with the new monoclonal antibodies 1H7, 5C1, or 5D12, all directed against the CT of α-syn. CT α-syn antibodies attenuated synaptic and axonal pathology, reduced the accumulation of CT-truncated α-syn (CT-α-syn) in axons, rescued the loss of tyrosine hydroxylase fibers in striatum, and improved motor and memory deficits. Among them, 1H7 and 5C1 were most effective at decreasing levels of CT-α-syn and higher-molecular-weight aggregates. Furthermore, in vitro studies showed that preincubation of recombinant α-syn with 1H7 and 5C1 prevented CT cleavage of α-syn. In a cell-based system, CT antibodies reduced cell-to-cell propagation of full-length α-syn, but not of the CT-α-syn that lacked the 118-126 aa recognition site needed for antibody binding. Furthermore, the results obtained after lentiviral expression of α-syn suggest that antibodies might be blocking the extracellular truncation of α-syn by calpain-1. Together, these results demonstrate that antibodies against the CT of α-syn reduce levels of CT-truncated fragments of the protein and its propagation, thus ameliorating PD-like pathology and improving behavioral and motor functions in a mouse model of this disease. Copyright © 2014 the authors 0270-6474/14/349441-14$15.00/0.

  5. Fluid Inclusion characteristics of syn-late orogenic Co-Ni-Cu-Au deposits in the Siegerland District of the Rhenish Massif, Germany

    NASA Astrophysics Data System (ADS)

    Wohlgemuth, Christoph; Hellmann, André; Meyer, Franz Michael

    2013-04-01

    The Siegerland District is located in the fold-and-thrust-belt of the Rhenish Massif and hosts various syn- late orogenic vein-hosted hydrothermal mineralization types. Peak-metamorphism and deformation occurred at 312-316 ± 10 Ma (Ahrendt et al., 1978) at pT-conditions of 280 - 320 °C and 0.7 - 1.4 kbar (Hein, 1993). The district is known for synorogenic siderite-quartz mineralization formed during peak-metamorphic conditions. At least 4 syn-late orogenic mineralization types are distinguished: Co-Ni-Cu-Au, Pb-Zn-Cu, Sb-Au and hematite-digenite-bornite mineralization (Hellmann et al., 2012b). Co-Ni-Cu-Au mineralization of the Siegerland District belongs to the recently defined class of metasediment hosted synorogenic Co-Cu-Au deposits (i.e. Slack et al, 2010). Ore minerals are Fe-Co-Ni sulpharsenides, bearing invisible gold, chalcopyrite, and minor As-bearing pyrite. The gangue is quartz. The alteration mineralogy comprises chlorite, illite-muscovite and quartz. The epigenetic quartz veins are closely related to the formation of reverse faults (Hellmann et al., 2011a). Microthermometric studies of fluid inclusions concerning the relationship between mineralization and microstructures have not been done so far for this deposit-class and this will be addressed here. Fluid inclusions are investigated in hydrothermally formed vein-quartz, selected from Co-Ni-Cu-Au mineralization bearing veins showing only minor overprints by later mineralization types. Two quartz generations are distinguished: subhedral quartz-I showing growth zonation and fine grained, recrystallized- and newly formed quartz-II grains forming irregular masses and fracture fillings in quartz-I. Co-Ni-Fe sulpharsenides and chalcopyrite are closely intergrown with quartz-II, implying their contemperaneous formation. However, fluid inclusions in quartz-II are often small, therefore fluid inclusions in quartz-I have been mostly investigated. In total, 180 inclusions from 4 different deposits have been

  6. α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading.

    PubMed

    Loria, Frida; Vargas, Jessica Y; Bousset, Luc; Syan, Sylvie; Salles, Audrey; Melki, Ronald; Zurzolo, Chiara

    2017-11-01

    Recent evidence suggests that disease progression in Parkinson's disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that α-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons. Interestingly, α-syn puncta are mainly found inside the lysosomal compartments of the recipient cells. However, differently from neurons, astrocytes are able to efficiently degrade fibrillar α-syn, suggesting an active role for these cells in clearing α-syn deposits. Astrocytes co-cultured with organotypic brain slices are able to take up α-syn fibrils from the slices. Altogether our data support a role for astrocytes in trapping and clearing α-syn pathological deposits in PD.

  7. The nuclear accumulation of alpha-synuclein is mediated by importin alpha and promotes neurotoxicity by accelerating the cell cycle.

    PubMed

    Ma, Kai-Li; Song, Lian-Kun; Yuan, Yu-He; Zhang, Ying; Han, Ning; Gao, Kai; Chen, Nai-Hong

    2014-07-01

    α-Synuclein (α-syn), a 14 kDa pre-synaptic protein, is widely involved in the Parkinson's disease (PD) pathogenesis. Recent studies have shown that the nuclear accumulation of α-syn might have a toxic effect. The main purpose of the present study was to explore which amino acid residues in α-syn are associated with its nuclear accumulation, the molecule(s) mediated the nuclear import of α-syn, and the role of α-syn accumulated in the nucleus. It has been noted that the nuclear import of α-syn may be mediated by importin α and that both the amino acid residues 1-60 and 103-140 of α-syn were indispensable for its nuclear import. After imported into the nucleus, the accumulated α-syn played a toxic role in both the PC12 cells and the C57 mice. Furthermore, α-syn-nuclear localization signal-injected mice showed behavioral symptoms associated with PD. Further studies performed in vitro showed that the toxicity of α-syn in the nucleus might be due to an interference of the cell cycle. Thus, it can be concluded that α-syn can accumulate in nucleus, which is mediated by importin α, and promote neurotoxicity by accelerating the cell cycle. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. The N-Terminal Residues 43 to 60 Form the Interface for Dopamine Mediated α-Synuclein Dimerisation

    PubMed Central

    Leong, Su Ling; Hinds, Mark G.; Connor, Andrea R.; Smith, David P.; Illes-Toth, Eva; Pham, Chi L. L.; Barnham, Kevin J.; Cappai, Roberto

    2015-01-01

    α-synuclein (α-syn) is a major component of the intracellular inclusions called Lewy bodies, which are a key pathological feature in the brains of Parkinson’s disease patients. The neurotransmitter dopamine (DA) inhibits the fibrillisation of α-syn into amyloid, and promotes α-syn aggregation into SDS-stable soluble oligomers. While this inhibition of amyloid formation requires the oxidation of both DA and the methionines in α-syn, the molecular basis for these processes is still unclear. This study sought to define the protein sequences required for the generation of oligomers. We tested N- (α-syn residues 43–140) and C-terminally (1–95) truncated α-syn, and found that similar to full-length protein both truncated species formed soluble DA:α-syn oligomers, albeit 1–95 had a different profile. Using nuclear magnetic resonance (NMR), and the N-terminally truncated α-syn 43–140 protein, we analysed the structural characteristics of the DA:α-syn 43–140 dimer and α-syn 43–140 monomer and found the dimerisation interface encompassed residues 43 to 60. Narrowing the interface to this small region will help define the mechanism by which DA mediates the formation of SDS-stable soluble DA:α-syn oligomers. PMID:25679387

  9. Suppression of α-synuclein toxicity and vesicle trafficking defects by phosphorylation at S129 in yeast depends on genetic context

    PubMed Central

    Sancenon, Vicente; Lee, Sue-Ann; Patrick, Christina; Griffith, Janice; Paulino, Amy; Outeiro, Tiago F.; Reggiori, Fulvio; Masliah, Eliezer; Muchowski, Paul J.

    2012-01-01

    The aggregation of α-synuclein (αSyn) is a neuropathologic hallmark of Parkinson's disease and other synucleinopathies. In Lewy bodies, αSyn is extensively phosphorylated, predominantly at serine 129 (S129). Recent studies in yeast have shown that, at toxic levels, αSyn disrupts Rab homeostasis, causing an initial endoplasmic reticulum-to-Golgi block that precedes a generalized trafficking collapse. However, whether αSyn phosphorylation modulates trafficking defects has not been evaluated. Here, we show that constitutive expression of αSyn in yeast impairs late-exocytic, early-endocytic and/or recycling trafficking. Although members of the casein kinase I (CKI) family phosphorylate αSyn at S129, they attenuate αSyn toxicity and trafficking defects by an S129 phosphorylation-independent mechanism. Surprisingly, phosphorylation of S129 modulates αSyn toxicity and trafficking defects in a manner strictly determined by genetic background. Abnormal endosome morphology, increased levels of the endosome marker Rab5 and co-localization of mammalian CKI with αSyn aggregates are observed in brain sections from αSyn-overexpressing mice and human synucleinopathies. Our results contribute to evidence that suggests αSyn-induced defects in endocytosis, exocytosis and/or recycling of vesicles involved in these cellular processes might contribute to the pathogenesis of synucleinopathies. PMID:22357655

  10. Synapsin I and Synapsin II regulate neurogenesis in the dentate gyrus of adult mice

    PubMed Central

    Barbieri, Raffaella; Contestabile, Andrea; Ciardo, Maria Grazia; Forte, Nicola; Marte, Antonella; Baldelli, Pietro; Benfenati, Fabio; Onofri, Franco

    2018-01-01

    Adult neurogenesis is emerging as an important player in brain functions and homeostasis, while impaired or altered adult neurogenesis has been associated with a number of neuropsychiatric diseases, such as depression and epilepsy. Here we investigated the possibility that synapsins (Syns) I and II, beyond their known functions in developing and mature neurons, also play a role in adult neurogenesis. We performed a systematic evaluation of the distinct stages of neurogenesis in the hippocampal dentate gyrus of Syn I and Syn II knockout (KO) mice, before (2-months-old) and after (6-months-old) the appearance of the epileptic phenotype. We found that Syns I and II play an important role in the regulation of adult neurogenesis. In juvenile mice, Syn II deletion was associated with a specific decrease in the proliferation of neuronal progenitors, whereas Syn I deletion impaired the survival of newborn neurons. These defects were reverted after the appearance of the epileptic phenotype, with Syn I KO and Syn II KO mice exhibiting significant increases in survival and proliferation, respectively. Interestingly, long-term potentiation dependent on newborn neurons was present in both juvenile Syn mutants while, at later ages, it was only preserved in Syn II KO mice that also displayed an increased expression of brain-derived neurotrophic factor. This study suggests that Syns I and II play a role in adult neurogenesis and the defects in neurogenesis associated with Syn deletion may contribute to the alterations of cognitive functions observed in Syn-deficient mice. PMID:29721159

  11. Synapsin I and Synapsin II regulate neurogenesis in the dentate gyrus of adult mice.

    PubMed

    Barbieri, Raffaella; Contestabile, Andrea; Ciardo, Maria Grazia; Forte, Nicola; Marte, Antonella; Baldelli, Pietro; Benfenati, Fabio; Onofri, Franco

    2018-04-10

    Adult neurogenesis is emerging as an important player in brain functions and homeostasis, while impaired or altered adult neurogenesis has been associated with a number of neuropsychiatric diseases, such as depression and epilepsy. Here we investigated the possibility that synapsins (Syns) I and II, beyond their known functions in developing and mature neurons, also play a role in adult neurogenesis. We performed a systematic evaluation of the distinct stages of neurogenesis in the hippocampal dentate gyrus of Syn I and Syn II knockout (KO) mice, before (2-months-old) and after (6-months-old) the appearance of the epileptic phenotype. We found that Syns I and II play an important role in the regulation of adult neurogenesis. In juvenile mice, Syn II deletion was associated with a specific decrease in the proliferation of neuronal progenitors, whereas Syn I deletion impaired the survival of newborn neurons. These defects were reverted after the appearance of the epileptic phenotype, with Syn I KO and Syn II KO mice exhibiting significant increases in survival and proliferation, respectively. Interestingly, long-term potentiation dependent on newborn neurons was present in both juvenile Syn mutants while, at later ages, it was only preserved in Syn II KO mice that also displayed an increased expression of brain-derived neurotrophic factor. This study suggests that Syns I and II play a role in adult neurogenesis and the defects in neurogenesis associated with Syn deletion may contribute to the alterations of cognitive functions observed in Syn-deficient mice.

  12. Epothilone D inhibits microglia-mediated spread of alpha-synuclein aggregates.

    PubMed

    Valdinocci, Dario; Grant, Gary D; Dickson, Tracey C; Pountney, Dean L

    2018-04-16

    Multiple System Atrophy (MSA) is a progressive neurodegenerative disease characterized by chronic neuroinflammation and widespread α-synuclein (α-syn) cytoplasmic inclusions. Neuroinflammation associated with microglial cells is typically located in brain regions with α-syn deposits. The potential link between microglial cell migration and the transport of pathological α-syn protein in MSA was investigated. Qualitative analysis via immunofluorescence of MSA cases (n = 4) revealed microglial cells bearing α-syn inclusions distal from oligodendrocytes bearing α-syn cytoplasmic inclusions, as well as close interactions between microglia and oligodendrocytes bearing α-syn, suggestive of a potential transfer mechanism between microglia and α-syn bearing cells in MSA and the possibility of microglia acting as a mobile vehicle to spread α-syn between anatomically connected brain regions. Further In vitro experiments using microglial-like differentiated THP-1 cells were conducted to investigate if microglial cells could act as potential transporters of α-syn. Monomeric or aggregated α-syn was immobilized at the centre of glass coverslips and treated with either cell free medium, undifferentiated THP-1 cells or microglial-like phorbol-12-myristate-13-acetate differentiated THP-1 cells (48 h; n = 3). A significant difference in residual immobilized α-syn density was observed between cell free controls and differentiated (p = 0.016) as well as undifferentiated and differentiated THP-1 cells (p = 0.032) when analysed by quantitative immunofluorescence. Furthermore, a significantly greater proportion of differentiated cells were observed bearing α-syn aggregates distal from the immobilized protein than their non-differentiated counterparts (p = 0.025). Similar results were observed with Highly Aggressive Proliferating Immortalised (HAPI) microglial cells, with cells exposed to aggregated α-syn yielding lower residual immobilized α-syn (p

  13. Helminths of lizards from the municipality of Aripuanã in the southern Amazon region of Brazil.

    PubMed

    Ávila, R W; da Silva, R J

    2013-03-01

    Ninety-five specimens from 13 species of lizard collected during a herpetofaunal monitoring programme of the Faxinal II power plant, municipality of Aripuanã, state of Mato Grosso, Brazil (southern Amazon region) were examined for helminths. A total of 21 helminth species (16 Nematoda, 1 Cestoda and 4 Trematoda) were recovered, with an overall prevalence of 67.37%. Seventeen new host records and seven new locality records are reported. A low number of specialists and core helminth species were found. Lizard body size was positively correlated with both the total number of helminth species and individuals. Active foragers exhibited higher helminth diversity. However, sit-and-wait foragers, especially Plica plica, had similar diversity values as active foragers and harboured more helminth species. The degree of similarity in helminth fauna was higher among closely related host species.

  14. The viscosity of pāhoehoe lava: In situ syn-eruptive measurements from Kilauea, Hawaii

    NASA Astrophysics Data System (ADS)

    Chevrel, Magdalena Oryaëlle; Harris, Andrew J. L.; James, Mike R.; Calabrò, Laura; Gurioli, Lucia; Pinkerton, Harry

    2018-07-01

    Viscosity is one of the most important physical properties controlling lava flow dynamics. Usually, viscosity is measured in the laboratory where key parameters can be controlled but can never reproduce the natural environment and original state of the lava in terms of crystal and bubble contents, dissolved volatiles, and oxygen fugacity. The most promising approach for quantifying the rheology of molten lava in its natural state is therefore to carry out direct field measurements by inserting a viscometer into the lava while it is flowing. Such in-situ syn-eruptive viscosity measurements are notoriously difficult to perform due to the lack of appropriate instrumentation and the difficulty of working on or near an active lava flow. In the field, rotational viscometer measurements are of particular value as they have the potential to measure the properties of the flow interior rather than an integration of the viscosity of the viscoelastic crust + flow interior. To our knowledge only one field rotational viscometer is available, but logistical constraints have meant that it has not been used for 20 yr. Here, we describe new viscosity measurements made using the refurbished version of this custom-built rotational viscometer, as performed on active pāhoehoe lobes from the 61G lava flow of Kilauea's Pu'u 'Ō'ō eruption in 2016. We successfully measured a viscosity of ∼380 Pa s at strain-rates between 1.6 and 5 s-1 and at 1144 °C. Additionally, synchronous lava sampling allowed us to provide detailed textural and chemical characterization of quenched samples. Application of current physico-chemical models based on this characterization (16 ± 4 vol.% crystals; 50 ± 6 vol.% vesicles), gave viscosity estimates that were approximately compatible with the measured values, highlighting the sensitivity of model-based viscosity estimates on the effect of deformable bubbles. Our measurements also agree on the range of viscosities in comparison to previous field

  15. Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy

    PubMed Central

    Bassil, Fares; Fernagut, Pierre-Olivier; Bezard, Erwan; Pruvost, Alain; Leste-Lasserre, Thierry; Hoang, Quyen Q.; Ringe, Dagmar; Petsko, Gregory A.; Meissner, Wassilios G.

    2016-01-01

    Multiple system atrophy (MSA) is a sporadic orphan neurodegenerative disorder. No treatment is currently available to slow down the aggressive neurodegenerative process, and patients die within a few years after disease onset. The cytopathological hallmark of MSA is the accumulation of alpha-synuclein (α-syn) aggregates in affected oligodendrocytes. Several studies point to α-syn oligomerization and aggregation as a mediator of neurotoxicity in synucleinopathies including MSA. C-terminal truncation by the inflammatory protease caspase-1 has recently been implicated in the mechanisms that promote aggregation of α-syn in vitro and in neuronal cell models of α-syn toxicity. We present here an in vivo proof of concept of the ability of the caspase-1 inhibitor prodrug VX-765 to mitigate α-syn pathology and to mediate neuroprotection in proteolipid protein α-syn (PLP-SYN) mice, a transgenic mouse model of MSA. PLP-SYN and age-matched wild-type mice were treated for a period of 11 wk with VX-765 or placebo. VX-765 prevented motor deficits in PLP-SYN mice compared with placebo controls. More importantly, VX-765 was able to limit the progressive toxicity of α-syn aggregation by reducing its load in the striatum of PLP-SYN mice. Not only did VX-765 reduce truncated α-syn, but it also decreased its monomeric and oligomeric forms. Finally, VX-765 showed neuroprotective effects by preserving tyrosine hydroxylase-positive neurons in the substantia nigra of PLP-SYN mice. In conclusion, our results suggest that VX-765, a drug that was well tolerated in a 6 wk-long phase II trial in patients with epilepsy, is a promising candidate to achieve disease modification in synucleinopathies by limiting α-syn accumulation. PMID:27482103

  16. α-Synuclein Mutation Inhibits Endocytosis at Mammalian Central Nerve Terminals.

    PubMed

    Xu, Jianhua; Wu, Xin-Sheng; Sheng, Jiansong; Zhang, Zhen; Yue, Hai-Yuan; Sun, Lixin; Sgobio, Carmelo; Lin, Xian; Peng, Shiyong; Jin, Yinghui; Gan, Lin; Cai, Huaibin; Wu, Ling-Gang

    2016-04-20

    α-Synuclein (α-syn) missense and multiplication mutations have been suggested to cause neurodegenerative diseases, including Parkinson's disease (PD) and dementia with Lewy bodies. Before causing the progressive neuronal loss, α-syn mutations impair exocytosis, which may contribute to eventual neurodegeneration. To understand how α-syn mutations impair exocytosis, we developed a mouse model that selectively expressed PD-related human α-syn A53T (h-α-synA53T) mutation at the calyx of Held terminals, where release mechanisms can be dissected with a patch-clamping technique. With capacitance measurement of endocytosis, we reported that h-α-synA53T, either expressed transgenically or dialyzed in the short term in calyces, inhibited two of the most common forms of endocytosis, the slow and rapid vesicle endocytosis at mammalian central synapses. The expression of h-α-synA53Tin calyces also inhibited vesicle replenishment to the readily releasable pool. These findings may help to understand how α-syn mutations impair neurotransmission before neurodegeneration. α-Synuclein (α-syn) missense or multiplication mutations may cause neurodegenerative diseases, such as Parkinson's disease and dementia with Lewy bodies. The initial impact of α-syn mutations before neuronal loss is impairment of exocytosis, which may contribute to eventual neurodegeneration. The mechanism underlying impairment of exocytosis is poorly understood. Here we report that an α-syn mutant, the human α-syn A53T, inhibited two of the most commonly observed forms of endocytosis, slow and rapid endocytosis, at a mammalian central synapse. We also found that α-syn A53T inhibited vesicle replenishment to the readily releasable pool. These results may contribute to accounting for the widely observed early synaptic impairment caused by α-syn mutations in the progression toward neurodegeneration. Copyright © 2016 the authors 0270-6474/16/364408-07$15.00/0.

  17. Distinct roles of neuroligin-1 and SynCAM1 in synapse formation and function in primary hippocampal neuronal cultures.

    PubMed

    Burton, S D; Johnson, J W; Zeringue, H C; Meriney, S D

    2012-07-26

    Neuroligins are a family of cell adhesion molecules critical in establishing proper central nervous system connectivity; disruption of neuroligin signaling in vivo precipitates a broad range of cognitive deficits. Despite considerable recent progress, the specific synaptic function of neuroligin-1 (NL1) remains unclear. A current model proposes that NL1 acts exclusively to mature pre-existent synaptic connections in an activity-dependent manner. A second element of this activity-dependent maturation model is that an alternate molecule acts upstream of NL1 to initiate synaptic connections. SynCAM1 (SC1) is hypothesized to function in this capacity, though several uncertainties remain regarding SC1 function. Using overexpression and chronic pharmacological blockade of synaptic activity, we now demonstrate that NL1 is capable of robustly recruiting synapsin-positive terminals independent of synaptic maturation and activity in 2-week old primary hippocampal neuronal cultures. We further report that neither SC1 overexpression nor knockdown of endogenous SC1 impacts synapsin punctum densities, suggesting that SC1 is not a limiting factor of synapse initiation in maturing hippocampal neurons in vitro. Consistent with these findings, we observed profoundly greater recruitment of synapsin-positive presynaptic terminals by NL1 than SC1 in a mixed-culture assay of artificial synaptogenesis between primary neurons and heterologous cells. Collectively, our results contend multiple aspects of the proposed model of NL1 and SC1 function and motivate an alternative model whereby SC1 may mature synaptic connections forged by NL1. Supporting this model, we present evidence that combined NL1 and SC1 overexpression triggers excitotoxic neurodegeneration through SC1 signaling at synaptic connections initiated by NL1. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate), Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy

    PubMed Central

    Schwab, Karima; Frahm, Silke; Horsley, David; Rickard, Janet E.; Melis, Valeria; Goatman, Elizabeth A.; Magbagbeolu, Mandy; Douglas, Morag; Leith, Michael G.; Baddeley, Thomas C.; Storey, John M. D.; Riedel, Gernot; Wischik, Claude M.; Harrington, Charles R.; Theuring, Franz

    2018-01-01

    α-Synuclein (α-Syn) aggregation is a pathological feature of synucleinopathies, neurodegenerative disorders that include Parkinson’s disease (PD). We have tested whether N,N,N′,N′-tetramethyl-10H-phenothiazine-3,7-diaminium bis(hydromethanesulfonate) (leuco-methylthioninium bis(hydromethanesulfonate); LMTM), a tau aggregation inhibitor, affects α-Syn aggregation in vitro and in vivo. Both cellular and transgenic models in which the expression of full-length human α-Syn (h-α-Syn) fused with a signal sequence peptide to promote α-Syn aggregation were used. Aggregated α-Syn was observed following differentiation of N1E-115 neuroblastoma cells transfected with h-α-Syn. The appearance of aggregated α-Syn was inhibited by LMTM, with an EC50 of 1.1 μM, with minimal effect on h-α-Syn mRNA levels being observed. Two independent lines of mice (L58 and L62) transgenic for the same fusion protein accumulated neuronal h-α-Syn that, with aging, developed into fibrillary inclusions characterized by both resistance to proteinase K (PK)-cleavage and their ability to bind thiazin red. There was a significant decrease in α-Syn-positive neurons in multiple brain regions following oral treatment of male and female mice with LMTM administered daily for 6 weeks at 5 and 15 mg MT/kg. The early aggregates of α-Syn and the late-stage fibrillar inclusions were both susceptible to inhibition by LMTM, a treatment that also resulted in the rescue of movement and anxiety-related traits in these mice. The results suggest that LMTM may provide a potential disease modification therapy in PD and other synucleinopathies through the inhibition of α-Syn aggregation. PMID:29375308

  19. Preparation and Characterization of Stable α-Synuclein Lipoprotein Particles.

    PubMed

    Eichmann, Cédric; Campioni, Silvia; Kowal, Julia; Maslennikov, Innokentiy; Gerez, Juan; Liu, Xiaoxia; Verasdonck, Joeri; Nespovitaya, Nadezhda; Choe, Senyon; Meier, Beat H; Picotti, Paola; Rizo, Josep; Stahlberg, Henning; Riek, Roland

    2016-04-15

    Multiple neurodegenerative diseases are caused by the aggregation of the human α-Synuclein (α-Syn) protein. α-Syn possesses high structural plasticity and the capability of interacting with membranes. Both features are not only essential for its physiological function but also play a role in the aggregation process. Recently it has been proposed that α-Syn is able to form lipid-protein particles reminiscent of high-density lipoproteins. Here, we present a method to obtain a stable and homogeneous population of nanometer-sized particles composed of α-Syn and anionic phospholipids. These particles are called α-Syn lipoprotein (nano)particles to indicate their relationship to high-density lipoproteins formed by human apolipoproteins in vivo and of in vitro self-assembling phospholipid bilayer nanodiscs. Structural investigations of the α-Syn lipoprotein particles by circular dichroism (CD) and magic angle solid-state nuclear magnetic resonance (MAS SS-NMR) spectroscopy establish that α-Syn adopts a helical secondary structure within these particles. Based on cryo-electron microscopy (cryo-EM) and dynamic light scattering (DLS) α-Syn lipoprotein particles have a defined size with a diameter of ∼23 nm. Chemical cross-linking in combination with solution-state NMR and multiangle static light scattering (MALS) of α-Syn particles reveal a high-order protein-lipid entity composed of ∼8-10 α-Syn molecules. The close resemblance in size between cross-linked in vitro-derived α-Syn lipoprotein particles and a cross-linked species of endogenous α-Syn from SH-SY5Y human neuroblastoma cells indicates a potential functional relevance of α-Syn lipoprotein nanoparticles. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Intestinal helminths infection of rats (Ratus norvegicus) in the Belgrade area (Serbia): the effect of sex, age and habitat.

    PubMed

    Kataranovski, M; Mirkov, I; Belij, S; Popov, A; Petrovic, Z; Gaci, Z; Kataranovski, D

    2011-05-01

    Gastrointestinal helminths of Norway rat (Rattus norvegicus) from the Belgrade area were studied as a part of a wider ecological research of rats in Serbia (data on the distribution, population ecology, economic and epizoothiological-epidemiological importance, and density control). Rats were captured from May 2005 to July 2009 at both urban and suburban-rural sites. Of a total of 302 trapped rats 48% were males and 52% females, with 36.5% and 38.8% of juvenile-subadult individuals, per sex respectively. Intestinal helminth infection was noted in 68.5% of rats, with a higher prevalence in male hosts and in adult individuals. Higher numbers of infected juveniles-subadults were noted in suburban-rural habitats, while an opposite tendency was noted in adult rats. Seven helminth species were recovered, of which five were nematode (Heterakis spumosa, Nippostrongylus brasiliensis, Capillaria sp., Trichuris muns and Syphacia muris) and two cestode species (Hymenolepis diminuta and Rodentolepis fraterna). The most prevalent parasites were Heterakis spumosa (36.7%) and Hymenolepis diminuta (30.5 %). Sex and habitat-related differences were noted in the prevalence of infection with Capillaria sp. and Trichuris muris, while there were no age-related differences in the prevalence of infection with any individual helminth species. Significantly higher prevalence of infection was noted in summer as compared to spring or winter, with a tendency to be higher in autumn as compared to spring. The only significant difference in the prevalence of infection between habitat-related was noted during spring. H. spumosa was most prevalent in summer, while H. diminuta and N. brasiliensis in autumn. The mean intensity of infection with H. spumosa, R. fraterna, S. muris and T muris was higher in autumn than in the other seasons, while N. brasiliensis and Capillaria sp. occured in winter. No more than four helminth species were found in one host.

  1. Intestinal helminths infection of rats (Ratus norvegicus) in the Belgrade area (Serbia): the effect of sex, age and habitat*

    PubMed Central

    Kataranovski, M.; Mirkov, I.; Belij, S.; Popov, A.; Petrović, Z.; Gačić, Z.; Kataranovski, D.

    2011-01-01

    Gastrointestinal helminths of Norway rat (Rattus norvegicus) from the Belgrade area were studied as a part of a wider ecological research of rats in Serbia (data on the distribution, population ecology, economic and epizoothiological-epidemiological importance, and density control). Rats were captured from May 2005 to July 2009 at both urban and suburban-rural sites. Of a total of 302 trapped rats 48% were males and 52% females, with 36.5% and 38.8% of juvenile-subadult individuals, per sex respectively. Intestinal helminth infection was noted in 68.5% of rats, with a higher prevalence in male hosts and in adult individuals. Higher numbers of infected juveniles-subadults were noted in suburban-rural habitats, while an opposite tendency was noted in adult rats. Seven helminth species were recovered, of which five were nematode (Heterakis spumosa, Nippostrongylus brasiliensis, Capillaria sp., Trichuris muris and Syphacia muris) and two cestode species (Hymenolepis diminuta and Rodentolepis fraterna). The most prevalent parasites were Heterakis spumosa (36.7%) and Hymenolepis diminuta (30.5%). Sex and habitat-related differences were noted in the prevalence of infection with Capillaria sp. and Trichuris muris, while there were no age-related differences in the prevalence of infection with any individual helminth species. Significantly higher prevalence of infection was noted in summer as compared to spring or winter, with a tendency to be higher in autumn as compared to spring. The only significant difference in the prevalence of infection between habitat-related was noted during spring. H. spumosa was most prevalent in summer, while H. diminuta and N. brasiliensis in autumn. The mean intensity of infection with H. spumosa, R. fraterna, S. muris and T. muris was higher in autumn than in the other seasons, while N. brasiliensis and Capillaria sp. occured in winter. No more than four helminth species were found in one host. PMID:21678796

  2. Nomenclatural Studies Toward a World List of Diptera Genus-Group Names. Part V: Pierre-Justin-Marie Macquart.

    PubMed

    Evenhuis, Neal L; Pape, Thomas; Pont, Adrian C

    2016-09-30

    [Ephydridae]; Pleurocerina Macquart, 1851[Conopidae]; Pteropexus Macquart, 1846 [Acroceridae]; Semiomyia Macquart, 1848 [Tachinidae]; Teremyia Macquart, 1835 [Lonchaeidae].        The following names are new synonymies of their respective senior synonyms: -genus-group names: Acemyia Macquart, 1834 of Acemya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Acrochoeta Macquart, 1835 of Acrochaeta Wiedemann, 1830, n. syn. [Stratiomyidae]; Atractea Agassiz, 1846 of Atractia Macquart, 1838, n. syn. [Asilidae]; Aulacocephala Brauer, 1863 of Aulacephala Macquart, 1851, n. syn. [Tachinidae]; Beckeriella Williston, 1897 of Notacanthina Macquart, 1834, n. syn. [Ephydridae]; Caenosia Macquart, 1835 of Coenosia Meigen, 1826, n. syn. [Muscidae]; Ceromyia Macquart, 1834 of Ceromya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Chiromysa Macquart, 1835 of Chiromyza Wiedemann, 1820, n. syn. [Stratiomyidae]; Chrisochlora Macquart, 1835 of Chrysochlora Latreille, 1829, n. syn. [Stratiomyidae]; Chrysopyla Macquart, 1840 of Chrysopilus Macquart, 1826, n. syn. [Rhagionidae]; Cleigaster Macquart, 1844 of Cleigastra Macquart, 1835, n. syn. [Scathophagidae]; Clyto Macquart, 1835 of Clytho Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Cordylura Macquart, 1835 of Cordilura Fallén, 1810, n. syn. [Scathophagidae]; Craspedochaeta Marschall, 1873 of Anthomyia Meigen, 1803, n. syn. [Anthomyiidae]; Cyrtonevra Agassiz, 1846 of Graphomya Robineau-Desvoidy, 1830, n. syn. [Muscidae]; Diaphora Macquart, 1834 of Diaphorus Meigen, 1824, n. syn. [Dolichopodidae]; Dichoeta Macquart, 1835 of Dichaeta Meigen, 1830, n. syn. [Ephydridae]; Dichromyia Macquart, 1844 of Dichromya Robineau-Desvoidy, 1830, n. syn. [Heleomyzidae]; Diphysa Macquart, 1838 of Archistratiomys Enderlein, 1913, n. syn. [Stratiomyidae]; Echinomyia Fischer von Waldheim, 1808 of Tachina Meigen, 1803, n. syn. [Tachinidae]; Egina Macquart, 1835 of Eginia Robineau-Desvoidy, 1830, n. syn. [Muscidae]; Hematobia Macquart, 1850 of Haematobia Le

  3. Eucoleus aerophilus respiratory infection in a dog with Addison’s disease

    PubMed Central

    Burgess, Hilary; Ruotsalo, Kristiina; Peregrine, Andrew S.; Hanselman, Beth; Abrams-Ogg, Anthony

    2008-01-01

    A 4-year-old, standard poodle was presented to the Ontario Veterinary College for a 3-week history of a moist, productive cough that was first noted while boarding at a kennel. Bronchoalveolar lavage revealed numerous ova identified as Eucoleus aerophilus, previously known as Capillaria aerophila. Clinical signs resolved following treatment with fenbendazole. PMID:18481549

  4. Ubiquitinylation of α-Synuclein by Carboxyl Terminus Hsp70-Interacting Protein (CHIP) Is Regulated by Bcl-2-Associated Athanogene 5 (BAG5)

    PubMed Central

    Chau, Hien; Lozano, Andres M.; Hyman, Bradley T.; McLean, Pamela J.

    2011-01-01

    Parkinson's disease (PD) is a common neurodegenerative condition in which abnormalities in protein homeostasis, or proteostasis, may lead to accumulation of the protein α-synuclein (α-syn). Mutations within or multiplications of the gene encoding α-syn are known to cause genetic forms of PD and polymorphisms in the gene are recently established risk factors for idiopathic PD. α-syn is a major component of Lewy bodies, the intracellular proteinaceous inclusions which are pathological hallmarks of most forms of PD. Recent evidence demonstrates that α-syn can self associate into soluble oligomeric species and implicates these α-syn oligomers in cell death. We have previously shown that carboxyl terminus of Hsp70-interacting protein (CHIP), a co-chaperone molecule with E3 ubiquitin ligase activity, may reduce the levels of toxic α-syn oligomers. Here we demonstrate that α-syn is ubiquitinylated by CHIP both in vitro and in cells. We find that the products from ubiquitinylation by CHIP include both monoubiquitinylated and polyubiquitinylated forms of α-syn. We also demonstrate that CHIP and α-syn exist within a protein complex with the co-chaperone bcl-2-associated athanogene 5 (BAG5) in brain. The interaction of CHIP with BAG5 is mediated by Hsp70 which binds to the tetratricopeptide repeat domain of CHIP and the BAG domains of BAG5. The Hsp70-mediated association of BAG5 with CHIP results in inhibition of CHIP E3 ubiquitin ligase activity and subsequently reduces α-syn ubiquitinylation. Furthermore, we use a luciferase-based protein-fragment complementation assay of α-syn oligomerization to investigate regulation of α-syn oligomers by CHIP in living cells. We demonstrate that BAG5 mitigates the ability of CHIP to reduce α-syn oligomerization and that non-ubiquitinylated α-syn has an increased propensity for oligomerization. Thus, our results identify CHIP as an E3 ubiquitin ligase of α-syn and suggest a novel function for BAG5 as a modulator of CHIP E3

  5. α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's disease.

    PubMed

    Kang, Seong Su; Ahn, Eun Hee; Zhang, Zhentao; Liu, Xia; Manfredsson, Fredric P; Sandoval, Ivette M; Dhakal, Susov; Iuvone, P Michael; Cao, Xuebing; Ye, Keqiang

    2018-06-15

    Dopaminergic neurodegeneration in Parkinson's disease (PD) is associated with abnormal dopamine metabolism by MAO-B (monoamine oxidase-B) and intracellular α-Synuclein (α-Syn) aggregates, called the Lewy body. However, the molecular relationship between α-Syn and MAO-B remains unclear. Here, we show that α-Syn directly binds to MAO-B and stimulates its enzymatic activity, which triggers AEP (asparagine endopeptidase; legumain) activation and subsequent α-Syn cleavage at N103, leading to dopaminergic neurodegeneration. Interestingly, the dopamine metabolite, DOPAL, strongly activates AEP, and the N103 fragment of α-Syn binds and activates MAO-B. Accordingly, overexpression of AEP in SNCA transgenic mice elicits α-Syn N103 cleavage and accelerates PD pathogenesis, and inhibition of MAO-B by Rasagiline diminishes α-Syn-mediated PD pathology and motor dysfunction. Moreover, virally mediated expression of α-Syn N103 induces PD pathogenesis in wild-type, but not MAO-B-null mice. Our findings thus support that AEP-mediated cleavage of α-Syn at N103 is required for the association and activation of MAO-B, mediating PD pathogenesis. © 2018 The Authors.

  6. Taxonomic changes in African Stratiomyidae (Diptera).

    PubMed

    Hauser, Martin; Woodley, Norman E; Fachin, Diego A

    2017-05-08

    Thirteen new generic synonyms, nineteen species synonyms and forty-eight new combinations of African Stratiomyidae are proposed (senior synonym in parentheses):Arthronemina Lindner in James, 1980 syn. nov. (=Argyrobrithes Grünberg, 1915), Arthronema Lindner, 1966b syn. nov. (=Argyrobrithes Grünberg, 1915), Brachyphleps Lindner, 1965 syn. nov. (=Psapharomys Grünberg, 1915), Dinosargus Lindner, 1968 syn. nov. (=Gongrosargus Lindner, 1959), Dolichodema Kertész, 1916 syn. nov. (=Thorasena Macquart, 1838), Gobertina Bigot, 1879a syn. nov. (=Sternobrithes Loew, 1857), Himantochaeta Lindner, 1939 syn. nov. (=Nyplatys Séguy, 1938), Hypoxycera Lindner 1966a syn. nov. (=Hypoceromys Lindner, 1935), Leucacron Lindner, 1966b syn. nov. (=Ptilinoxus Lindner, 1966b), Lonchobrithes Lindner, 1968 syn. nov. (=Argyrobrithes Grünberg, 1915), Meristomeringella Lindner 1965 syn. nov. (=Hypoceromys Lindner, 1935), Physometopon Lindner, 1966b syn. nov. (=Cardopomyia Kertész, 1916), Psapharomydops Lindner, 1966a syn. nov. (=Steleoceromys Grünberg, 1915), Adoxomyia grisea (Séguy, 1931) syn. nov. (=Adoxomyia argenteofasciata (Bezzi, 1906)), Argyrobrithes argenteus Grünberg, 1915 syn. nov. (=Argyrobrithes fuscicornis (Bezzi, 1914)), Argyrobrithes crinitus Lindner, 1972 syn. nov. (=Argyrobrithes zernyi Lindner, 1943), Brachyphleps tristis Lindner, 1965 syn. nov. (=Psapharomys salebrosa Grünberg, 1915), Chrysochroma laetum Lindner, 1966b syn. nov. (=Ptectisargus abditus (Lindner, 1936), Dolichodema africana Kertész, 1916 syn. nov. (=Thorasena pectoralis (Wiedemann, 1838)), Gongrosargus distinguendus Lindner, 1966c syn. nov. (=Gongrosargus glaucus (Bigot, 1859)), Gongrosargus exclamationis Lindner, 1968 syn. nov. (=Gongrosargus pallidus (Macquart, 1838)), Gongrosargus univittatus Lindner, 1966b syn. nov. (=Gongrosargus pallidus (Macquart, 1838)), Hypoxycera simplex Lindner, 1966a syn. nov. (=Hypoceromys jamesi (Lindner, 1965)), Lonchobrithes modestus Lindner, 1968 syn. nov

  7. Generic revision of the ant subfamily Dorylinae (Hymenoptera, Formicidae)

    PubMed Central

    Borowiec, Marek L.

    2016-01-01

    Abstract The generic classification of the ant subfamily Dorylinae is revised, with the aim of facilitating identification of easily-diagnosable monophyletic genera. The new classification is based on recent molecular phylogenetic evidence and a critical reappraisal of doryline morphology. New keys and diagnoses based on workers and males are provided, along with reviews of natural history and phylogenetic relationships, distribution maps, and a list of valid species for each lineage. Twenty-eight genera (27 extant and 1 extinct) are recognized within the subfamily, an increase from 20 in the previous classification scheme. Species classified in the polyphyletic Cerapachys and Sphinctomyrmex prior to this publication are here distributed among 9 and 3 different genera, respectively. Amyrmex and Asphinctanilloides are synonymized under Leptanilloides and the currently recognized subgenera are synonymized for Dorylus. No tribal classification is proposed for the subfamily, but several apparently monophyletic genus-groups are discussed. Valid generic names recognized here include: Acanthostichus (= Ctenopyga), Aenictogiton, Aenictus (= Paraenictus, Typhlatta), Cerapachys (= Ceratopachys), Cheliomyrmex, Chrysapace gen. rev., Cylindromyrmex (= Holcoponera, Hypocylindromyrmex, Metacylindromyrmex), Dorylus (= Alaopone syn. n., Anomma syn. n., Cosmaecetes, Dichthadia syn. n., Rhogmus syn. n., Shuckardia, Sphecomyrmex, Sphegomyrmex, Typhlopone syn. n.), Eburopone gen. n., Eciton (= Camptognatha, Holopone, Mayromyrmex), Eusphinctus gen. rev., Labidus (= Nycteresia, Pseudodichthadia), Leptanilloides (= Amyrmex syn. n., Asphinctanilloides syn. n.), Lioponera gen. rev. (= Neophyracaces syn. n., Phyracaces syn. n.), Lividopone, Neivamyrmex (= Acamatus, Woitkowskia), Neocerapachys gen. n., Nomamyrmex, Ooceraea gen. rev. (= Cysias syn. n.), Parasyscia gen. rev., †Procerapachys, Simopone, Sphinctomyrmex, Syscia gen. rev., Tanipone, Vicinopone, Yunodorylus gen. rev., Zasphinctus

  8. Effect of acidic pH on the stability of α-synuclein dimers.

    PubMed

    Lv, Zhengjian; Krasnoslobodtsev, Alexey V; Zhang, Yuliang; Ysselstein, Daniel; Rochet, Jean Christophe; Blanchard, Scott C; Lyubchenko, Yuri L

    2016-10-01

    Environmental factors, such as acidic pH, facilitate the assembly of α-synuclein (α-Syn) in aggregates, but the impact of pH on the very first step of α-Syn aggregation remains elusive. Recently, we developed a single-molecule approach that enabled us to measure directly the stability of α-Syn dimers. Unlabeled α-Syn monomers were immobilized on a substrate, and fluorophore-labeled monomers were added to the solution to allow them to form dimers with immobilized α-Syn monomers. The dimer lifetimes were measured directly from the fluorescence bursts on the time trajectories. Herein, we applied the single-molecule tethered approach for probing of intermolecular interaction to characterize the effect of acidic pH on the lifetimes of α-Syn dimers. The experiments were performed at pH 5 and 7 for wild-type α-Syn and for two mutants containing familial type mutations E46K and A53T. We demonstrate that a decrease of pH resulted in more than threefold increase in the α-Syn dimers lifetimes with some variability between the α-Syn species. We hypothesize that the stabilization effect is explained by neutralization of residues 96-140 of α-Syn and this electrostatic effect facilitates the association of the two monomers. Given that dimerization is the first step of α-Syn aggregation, we posit that the electrostatic effect thereby contributes to accelerating α-Syn aggregation at acidic pH. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 715-724, 2016. © 2016 Wiley Periodicals, Inc.

  9. Combined Active Humoral and Cellular Immunization Approaches for the Treatment of Synucleinopathies.

    PubMed

    Rockenstein, Edward; Ostroff, Gary; Dikengil, Fusun; Rus, Florentina; Mante, Michael; Florio, Jazmin; Adame, Anthony; Trinh, Ivy; Kim, Changyoun; Overk, Cassia; Masliah, Eliezer; Rissman, Robert A

    2018-01-24

    Dementia with Lewy bodies, Parkinson's disease, and Multiple System Atrophy are age-related neurodegenerative disorders characterized by progressive accumulation of α-synuclein (α-syn) and jointly termed synucleinopathies. Currently, no disease-modifying treatments are available for these disorders. Previous preclinical studies demonstrate that active and passive immunizations targeting α-syn partially ameliorate behavioral deficits and α-syn accumulation; however, it is unknown whether combining humoral and cellular immunization might act synergistically to reduce inflammation and improve microglial-mediated α-syn clearance. Since combined delivery of antigen plus rapamycin (RAP) in nanoparticles is known to induce antigen-specific regulatory T cells (Tregs), we adapted this approach to α-syn using the antigen-presenting cell-targeting glucan microparticle (GP) vaccine delivery system. PDGF-α-syn transgenic (tg) male and female mice were immunized with GP-alone, GP-α-syn (active humoral immunization), GP+RAP, or GP+RAP/α-syn (combined active humoral and Treg) and analyzed using neuropathological and biochemical markers. Active immunization resulted in higher serological total IgG, IgG1, and IgG2a anti-α-syn levels. Compared with mice immunized with GP-alone or GP-α-syn, mice vaccinated with GP+RAP or GP+RAP/α-syn displayed increased numbers of CD25-, FoxP3-, and CD4-positive cells in the CNS. GP-α-syn or GP+RAP/α-syn immunizations resulted in a 30-45% reduction in α-syn accumulation, neuroinflammation, and neurodegeneration. Mice immunized with GP+RAP/α-syn further rescued neurons and reduced neuroinflammation. Levels of TGF-β1 were increased with GP+RAP/α-syn immunization, while levels of TNF-α and IL-6 were reduced. We conclude that the observed effects of GP+RAP/α-syn immunization support the hypothesis that cellular immunization may enhance the effects of active immunotherapy for the treatment of synucleinopathies. SIGNIFICANCE STATEMENT We

  10. Revision of the fungus-farming ant genus Sericomyrmex Mayr (Hymenoptera, Formicidae, Myrmicinae)

    PubMed Central

    Ješovnik, Ana; Schultz, Ted R.

    2017-01-01

    Abstract The genus Sericomyrmex Mayr (Formicidae: Myrmicinae: Attini) is a Neotropical group of fungus-farming ants known for its problematic taxonomy, caused by low morphological variability across the species, vague and old species descriptions, and an outdated and incomplete key published in 1916. Recent molecular studies revealed that Sericomyrmex is the product of a rapid recent radiation, with a divergence date of 4.3 million years ago. Here we present a comprehensive taxonomic revision of the genus Sericomyrmex based on morphology and a recently published molecular phylogeny. We discuss and illustrate morphological characters for Sericomyrmex workers, males, queens, and larvae. We report 18 standard morphological measurements and 5 indices for 529 workers, 50 queens, and 39 males, which we employ in morphometric analyses. The revised genus Sericomyrmex comprises eleven species, including three new species, here described as S. maravalhas sp. n., S. radioheadi sp. n., and S. saramama sp. n. We also redescribe S. amabilis Wheeler, S. bondari Borgmeier, S. lutzi Wheeler, S. mayri Forel, S. opacus Mayr, S. parvulus Forel, S. saussurei Emery, and S. scrobifer Forel. The number of recognized species (11) is lower than the previously recognized 19 species and 3 subspecies. The following species and subspecies are synonymized: under S. opacus [=S. aztecus Forel syn. n., S. zacapanus Wheeler syn. n., and S. diego Forel syn. n.]; under S. bondari [=S. beniensis Weber syn. n.]; under S. mayri [=S. luederwaldti Santschi syn. n., S. moreirai Santschi syn. n., S. harekulli Weber syn. n., S. harekulli arawakensis Weber syn. n., S. urichi Forel syn. n.]; under S. saussurei [=S. burchelli Forel syn. n., S. impexus Wheeler syn. n., S. urichi maracas Weber syn. n.]; and under S. parvulus [=S. myersi Weber syn. n.]. We provide a key to Sericomyrmex species for the worker caste and information on the geographic distributions of all species. PMID:28769657

  11. A Focus on the Beneficial Effects of Alpha Synuclein and a Re-Appraisal of Synucleinopathies

    PubMed Central

    Ryskalin, Larisa; Busceti, Carla L.; Limanaqi, Fiona; Biagioni, Francesca; Gambardella, Stefano; Fornai, Francesco

    2018-01-01

    Alpha synuclein (α-syn) belongs to a class of proteins which are commonly considered to play a detrimental role in neuronal survival. This assumption is based on the occurrence of a severe neuronal degeneration in patients carrying a multiplication of the α-syn gene (SNCA) and in a variety of experi-mental models, where overexpression of α-syn leads to cell death and neurological impairment. In these conditions, a higher amount of normally structured α-syn produces a damage, which is even worse com-pared with that produced by α-syn owning an abnormal structure (as occurring following point gene muta-tions). In line with this, knocking out the expression of α-syn is reported to protect from specific neurotox-ins such as 1-methyl, 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP). In the present review we briefly dis-cuss these well-known detrimental effects but we focus on findings showing that, in specific conditions α-syn is beneficial for cell survival. This occurs during methamphetamine intoxication which is counteracted by endogenous α-syn. Similarly, the dysfunction of the chaperone cysteine-string protein-alpha leads to cell pathology which is counteracted by over-expressing α-syn. In line with this, an increased expression of α-syn protects against oxidative damage produced by dopamine. Remarkably, when the lack of α-syn is combined with a depletion of β- and γ- synucleins, alterations in brain structure and function occur. This review tries to balance the evidence showing a beneficial effect with the bulk of data reporting a detri-mental effect of endogenous α-syn. The specific role of α-syn as a chaperone protein is discussed to ex-plain such a dual effect. PMID:29150919

  12. A Focus on the Beneficial Effects of Alpha Synuclein and a Re-Appraisal of Synucleinopathies.

    PubMed

    Ryskalin, Larisa; Busceti, Carla L; Limanaqi, Fiona; Biagioni, Francesca; Gambardella, Stefano; Fornai, Francesco

    2018-01-01

    Alpha synuclein (α-syn) belongs to a class of proteins which are commonly considered to play a detrimental role in neuronal survival. This assumption is based on the occurrence of a severe neuronal degeneration in patients carrying a multiplication of the α-syn gene (SNCA) and in a variety of experimental models, where overexpression of α-syn leads to cell death and neurological impairment. In these conditions, a higher amount of normally structured α-syn produces a damage, which is even worse compared with that produced by α-syn owning an abnormal structure (as occurring following point gene mutations). In line with this, knocking out the expression of α-syn is reported to protect from specific neurotoxins such as 1-methyl, 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP). In the present review we briefly discuss these well-known detrimental effects but we focus on findings showing that, in specific conditions α-syn is beneficial for cell survival. This occurs during methamphetamine intoxication which is counteracted by endogenous α-syn. Similarly, the dysfunction of the chaperone cysteine-string protein- alpha leads to cell pathology which is counteracted by over-expressing α-syn. In line with this, an increased expression of α-syn protects against oxidative damage produced by dopamine. Remarkably, when the lack of α-syn is combined with a depletion of β- and γ- synucleins, alterations in brain structure and function occur. This review tries to balance the evidence showing a beneficial effect with the bulk of data reporting a detrimental effect of endogenous α-syn. The specific role of α-syn as a chaperone protein is discussed to explain such a dual effect. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. New systematic assignments in Gonyleptoidea (Arachnida, Opiliones, Laniatores)

    PubMed Central

    Pinto-da-Rocha, Ricardo; Benedetti, Alípio Rezende; de Vasconcelos, Eduardo Gomes; Hara, Marcos Ryotaro

    2012-01-01

    Abstract As part of an ongoing revision of the family Gonyleptidae, we have identified many species that are synonyms of previously described species or misplaced in this family. This article summarizes these findings, adding previously unavailable information or correcting imprecise observations to justify the presented taxonomic changes. The following new familial or subfamilial assignments are proposed: Nemastygnus Roewer, 1929 and Taulisa Roewer, 1956 are transferred to Agoristenidae, Agoristeninae; Napostygnus Roewer, 1929 to Cranaidae; Ceropachylinus peruvianus Roewer, 1956 and Pirunipygus Roewer, 1936 are transferred to Gonyleptidae, Ampycinae; Gyndesops Roewer, 1943, Haversia Roewer, 1913 and Oxapampeus Roewer, 1963 are transferred to Gonyleptidae, Pachylinae. The following generic synonymies are proposed for the family Gonyleptidae: Acanthogonyleptes Mello-Leitão, 1922 = Centroleptes Roewer, 1943; Acrographinotus Roewer, 1929 = Unduavius Roewer, 1929; Gonyleptes Kirby, 1819 = Collonychium Bertkau, 1880; Mischonyx Bertkau, 1880 = Eugonyleptes Roewer, 1913 and Gonazula Roewer, 1930; Parampheres Roewer, 1913 = Metapachyloides Roewer, 1917; Pseudopucrolia Roewer, 1912 = Meteusarcus Roewer, 1913; Haversia Roewer, 1913 = Hoggellula Roewer, 1930. The following specific synonymies are proposed for the family Gonyleptidae: Acanthogonyleptes singularis (Mello-Leitão, 1935) = Centroleptes flavus Roewer, 1943, syn. n.; Geraeocormobius sylvarum Holmberg, 1887 = Discocyrtus serrifemur Roewer, 1943, syn. n.; Gonyleptellus bimaculatus (Sørensen, 1884) = Gonyleptes cancellatus Roewer,1917, syn. n.; Gonyleptes atrus Mello-Leitão, 1923 = Weyhia brieni Giltay, 1928, syn. n.; Gonyleptes fragilis Mello-Leitão, 1923 = Gonyleptes banana Kury, 2003, syn. n.; Gonyleptes horridus Kirby, 1819 = Collonychium bicuspidatum Bertkau, 1880, syn. n., Gonyleptes borgmeyeri Mello-Leitão, 1932, syn. n., Gonyleptes curvicornis Mello-Leitão, 1932, syn. n., Metagonyleptes hamatus Roewer

  14. Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease.

    PubMed

    Masliah, Eliezer; Rockenstein, Edward; Mante, Michael; Crews, Leslie; Spencer, Brian; Adame, Anthony; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Rohn, Troy T; Mueller-Steiner, Sarah; Seubert, Peter; Barbour, Robin; McConlogue, Lisa; Buttini, Manuel; Games, Dora; Schenk, Dale

    2011-04-29

    Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB.

  15. Redox reactions of the α-synuclein-Cu(2+) complex and their effects on neuronal cell viability.

    PubMed

    Wang, Chengshan; Liu, Lin; Zhang, Lin; Peng, Yong; Zhou, Feimeng

    2010-09-21

    α-Synuclein (α-syn), a presynaptic protein believed to play an important role in neuropathology in Parkinson's disease (PD), is known to bind Cu(2+). Cu(2+) has been shown to accelerate the aggregation of α-syn to form various toxic aggregates in vitro. Copper is also a redox-active metal whose complexes with amyloidogenic proteins/peptides have been linked to oxidative stress in major neurodegenerative diseases. In this work, the formation of the Cu(2+) complex with α-syn or with an N-terminal peptide, α-syn(1-19), was confirmed with electrospray-mass spectrometry (ES-MS). The redox potentials of the Cu(2+) complex with α-syn (α-syn-Cu(2+)) and α-syn(1-19) were determined to be 0.018 and 0.053 V, respectively. Furthermore, the Cu(2+) center(s) can be readily reduced to Cu(+), and possible reactions of α-syn-Cu(2+) with cellular species (e.g., O(2), ascorbic acid, and dopamine) were investigated. The occurrence of a redox reaction can be rationalized by comparing the redox potential of the α-syn-Cu(2+) complex to that of the specific cellular species. For example, ascorbic acid can directly reduce α-syn-Cu(2+) to α-syn-Cu(+), setting up a redox cycle in which O(2) is reduced to H(2)O(2) and cellular redox species is continuously exhausted. In addition, the H(2)O(2) generated was demonstrated to reduce viability of the neuroblastoma SY-HY5Y cells. Although our results ruled out the direct oxidation of dopamine by α-syn-Cu(2+), the H(2)O(2) generated in the presence of α-syn-Cu(2+) can oxidize dopamine. Our results suggest that oxidative stress is at least partially responsible for the loss of dopaminergic cells in PD brain and reveal the multifaceted role of the α-syn-Cu(2+) complex in oxidative stress associated with PD symptoms.

  16. Mechanisms of α-Synuclein Induced Synaptopathy in Parkinson's Disease

    PubMed Central

    Bridi, Jessika C.; Hirth, Frank

    2018-01-01

    Parkinson's disease (PD) is characterized by intracellular inclusions of aggregated and misfolded α-Synuclein (α-Syn), and the loss of dopaminergic (DA) neurons in the brain. The resulting motor abnormalities mark the progression of PD, while non-motor symptoms can already be identified during early, prodromal stages of disease. Recent studies provide evidence that during this early prodromal phase, synaptic and axonal abnormalities occur before the degenerative loss of neuronal cell bodies. These early phenotypes can be attributed to synaptic accumulation of toxic α-Syn. Under physiological conditions, α-Syn functions in its native conformation as a soluble monomer. However, PD patient brains are characterized by intracellular inclusions of insoluble fibrils. Yet, oligomers and protofibrils of α-Syn have been identified to be the most toxic species, with their accumulation at presynaptic terminals affecting several steps of neurotransmitter release. First, high levels of α-Syn alter the size of synaptic vesicle pools and impair their trafficking. Second, α-Syn overexpression can either misregulate or redistribute proteins of the presynaptic SNARE complex. This leads to deficient tethering, docking, priming and fusion of synaptic vesicles at the active zone (AZ). Third, α-Syn inclusions are found within the presynaptic AZ, accompanied by a decrease in AZ protein levels. Furthermore, α-Syn overexpression reduces the endocytic retrieval of synaptic vesicle membranes during vesicle recycling. These presynaptic alterations mediated by accumulation of α-Syn, together impair neurotransmitter exocytosis and neuronal communication. Although α-Syn is expressed throughout the brain and enriched at presynaptic terminals, DA neurons are the most vulnerable in PD, likely because α-Syn directly regulates dopamine levels. Indeed, evidence suggests that α-Syn is a negative modulator of dopamine by inhibiting enzymes responsible for its synthesis. In addition, α-Syn

  17. CSF tau and β-amyloid predict cerebral synucleinopathy in autopsied Lewy body disorders.

    PubMed

    Irwin, David J; Xie, Sharon X; Coughlin, David; Nevler, Naomi; Akhtar, Rizwan S; McMillan, Corey T; Lee, Edward B; Wolk, David A; Weintraub, Daniel; Chen-Plotkin, Alice; Duda, John E; Spindler, Meredith; Siderowf, Andrew; Hurtig, Howard I; Shaw, Leslie M; Grossman, Murray; Trojanowski, John Q

    2018-03-20

    To test the association of antemortem CSF biomarkers with postmortem pathology in Lewy body disorders (LBD). Patients with autopsy-confirmed LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and cognitively normal (n = 36) controls were studied. In LBD, neuropathologic criteria defined Lewy body α-synuclein (SYN) stages with medium/high AD copathology (SYN + AD = 10) and low/no AD copathology (SYN - AD = 14). Ordinal pathology scores for tau, β-amyloid (Aβ), and SYN pathology were averaged across 7 cortical regions to obtain a global cerebral score for each pathology. CSF total tau (t-tau), phosphorylated tau at threonine 181 , and Aβ 1-42 levels were compared between LBD and control groups and correlated with global cerebral pathology scores in LBD with linear regression. Diagnostic accuracy for postmortem categorization of LBD into SYN + AD vs SYN - AD or neocortical vs brainstem/limbic SYN stage was tested with receiver operating curves. SYN + AD had higher CSF t-tau (mean difference 27.0 ± 8.6 pg/mL) and lower Aβ 1-42 (mean difference -84.0 ± 22.9 g/mL) compared to SYN - AD ( p < 0.01, both). Increasing global cerebral tau and plaque scores were associated with higher CSF t-tau ( R 2 = 0.15-0.16, p < 0.05, both) and lower Aβ 1-42 ( R 2 = 0.43-0.49, p < 0.001, both), while increasing cerebral SYN scores were associated with lower CSF Aβ 1-42 ( R 2 = 0.31, p < 0.001) and higher CSF t-tau/Aβ 1-42 ratio ( R 2 = 0.27, p = 0.01). CSF t-tau/Aβ 1-42 ratio had 100% specificity and 90% sensitivity for SYN + AD, and CSF Aβ 1-42 had 77% specificity and 82% sensitivity for neocortical SYN stage. Higher antemortem CSF t-tau/Aβ 1-42 and lower Aβ 1-42 levels are predictive of increasing cerebral AD and SYN pathology. These biomarkers may identify patients with LBD vulnerable to cortical SYN pathology who may benefit from both SYN and AD-targeted disease-modifying therapies. © 2018 American Academy of Neurology.

  18. The regulation of catalase activity by PPAR γ is affected by α-synuclein

    PubMed Central

    Yakunin, Eugenia; Kisos, Haya; Kulik, Willem; Grigoletto, Jessica; Wanders, Ronald J A; Sharon, Ronit

    2014-01-01

    Objective While evidence for oxidative injury is frequently detected in brains of humans affected by Parkinson's disease (PD) and in relevant animal models, there is uncertainty regarding its cause. We tested the potential role of catalase in the oxidative injury that characterizes PD. Methods Utilizing brains of A53T α-Syn and ntg mice, and cultured cells, we analyzed catalase activity and expression, and performed biochemical analyses of peroxisomal metabolites. Results Lower catalase expression and lower activity levels were detected in A53T α-Syn brains and α-Syn-expressing cells. The effect on catalase activity was independent of disease progression, represented by mouse age and α-Syn mutation, suggesting a potential physiological function for α-Syn. Notably, catalase activity and expression were unaffected in brains of mice modeling Alzheimer's disease. Moreover, we found that α-Syn expression downregulate the peroxisome proliferator-activated receptor (PPAR)γ, which controls catalase transcription. Importantly, activation of either PPARγ2, PPARα or retinoic X receptor eliminated the inhibiting effect of α-Syn on catalase activity. In addition, activation of these nuclear receptors enhanced the accumulation of soluble α-Syn oligomers, resulting in a positive association between the degree of soluble α-Syn oligomers and catalase activity. Of note, a comprehensive biochemical analysis of specific peroxisomal metabolites indicated no signs of dysfunction in specific peroxisomal activities in brains of A53T α-Syn mice. Interpretation Our results suggest that α-Syn expression may interfere with the complex and overlapping network of nuclear receptors transcription activation. In result, catalase activity is affected through mechanisms involved in the regulation of soluble α-Syn oligomers. PMID:25356396

  19. Structural and functional properties of prefibrillar α-synuclein oligomers.

    PubMed

    Pieri, Laura; Madiona, Karine; Melki, Ronald

    2016-04-14

    The deposition of fibrillar alpha-synuclein (α-syn) within inclusions (Lewy bodies and Lewy neurites) in neurons and glial cells is a hallmark of synucleinopathies. α-syn populates a variety of assemblies ranging from prefibrillar oligomeric species to fibrils whose specific contribution to neurodegeneration is still unclear. Here, we compare the specific structural and biological properties of distinct soluble prefibrillar α-syn oligomers formed either spontaneously or in the presence of dopamine and glutaraldehyde. We show that both on-fibrillar assembly pathway and distinct dopamine-mediated and glutaraldehyde-cross-linked α-syn oligomers are only slightly effective in perturbing cell membrane integrity and inducing cytotoxicity, while mature fibrils exhibit the highest toxicity. In contrast to low-molecular weight and unstable oligomers, large stable α-syn oligomers seed the aggregation of soluble α-syn within reporter cells although to a lesser extent than mature α-syn fibrils. These oligomers appear elongated in shape. Our findings suggest that α-syn oligomers represent a continuum of species ranging from unstable low molecular weight particles to mature fibrils via stable elongated oligomers composed of more than 15 α-syn monomers that possess seeding capacity.

  20. α-Synuclein Shows High Affinity Interaction with Voltage-dependent Anion Channel, Suggesting Mechanisms of Mitochondrial Regulation and Toxicity in Parkinson Disease*

    PubMed Central

    Rostovtseva, Tatiana K.; Gurnev, Philip A.; Protchenko, Olga; Hoogerheide, David P.; Yap, Thai Leong; Philpott, Caroline C.; Lee, Jennifer C.; Bezrukov, Sergey M.

    2015-01-01

    Participation of the small, intrinsically disordered protein α-synuclein (α-syn) in Parkinson disease (PD) pathogenesis has been well documented. Although recent research demonstrates the involvement of α-syn in mitochondrial dysfunction in neurodegeneration and suggests direct interaction of α-syn with mitochondria, the molecular mechanism(s) of α-syn toxicity and its effect on neuronal mitochondria remain vague. Here we report that at nanomolar concentrations, α-syn reversibly blocks the voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane that controls most of the metabolite fluxes in and out of the mitochondria. Detailed analysis of the blockage kinetics of VDAC reconstituted into planar lipid membranes suggests that α-syn is able to translocate through the channel and thus target complexes of the mitochondrial respiratory chain in the inner mitochondrial membrane. Supporting our in vitro experiments, a yeast model of PD shows that α-syn toxicity in yeast depends on VDAC. The functional interactions between VDAC and α-syn, revealed by the present study, point toward the long sought after physiological and pathophysiological roles for monomeric α-syn in PD and in other α-synucleinopathies. PMID:26055708

  1. Structural and functional properties of prefibrillar α-synuclein oligomers

    PubMed Central

    Pieri, Laura; Madiona, Karine; Melki, Ronald

    2016-01-01

    The deposition of fibrillar alpha-synuclein (α-syn) within inclusions (Lewy bodies and Lewy neurites) in neurons and glial cells is a hallmark of synucleinopathies. α-syn populates a variety of assemblies ranging from prefibrillar oligomeric species to fibrils whose specific contribution to neurodegeneration is still unclear. Here, we compare the specific structural and biological properties of distinct soluble prefibrillar α-syn oligomers formed either spontaneously or in the presence of dopamine and glutaraldehyde. We show that both on-fibrillar assembly pathway and distinct dopamine-mediated and glutaraldehyde-cross-linked α-syn oligomers are only slightly effective in perturbing cell membrane integrity and inducing cytotoxicity, while mature fibrils exhibit the highest toxicity. In contrast to low-molecular weight and unstable oligomers, large stable α-syn oligomers seed the aggregation of soluble α-syn within reporter cells although to a lesser extent than mature α-syn fibrils. These oligomers appear elongated in shape. Our findings suggest that α-syn oligomers represent a continuum of species ranging from unstable low molecular weight particles to mature fibrils via stable elongated oligomers composed of more than 15 α-syn monomers that possess seeding capacity. PMID:27075649

  2. Functional Results in Arthroscopic Treatment in Patients with Chronic Lateral Elbow Pain.

    PubMed

    Phorkhar, Termphong; Chanlalit, Cholawish

    2015-11-01

    Modern surgery as elbow arthroscopic surgery is an accepted operation due to benefit in precise intra-articular lesion detection and minimally invasive surgery. To report the functional results when using arthroscopic surgery to treat chronic lateral elbow pain. The data was collected from 25 patients with chronic lateral elbow pain that failed in non-operative treatment and treated with elbow arthroscopic surgery. Five patients were excluded from this study due to diagnosed as instability that needed the ligament reconstruction. The etiology of pain were grouped in to tennis elbow (4 pts), plica (9 pts), tennis elbow combined with plica (4 pts) and cartilage lesion (3 pts). Thai quick DASH questionnaire was used to evaluate the functional results by comparing pre and post operation score and calculated statistic results with paired t-test by level of significance p < 0.05. The mean follow-up after surgery was 22 months by mean disability module pre and post-operative score is 68 and 18 respectively. In the occupation module was 74 and 25 respectively and in sports module was 81 and 17 respectively. All modules, scores was significant improved with p-value = 0.000, 0.000 and 0.004 respectively. The disability mean score in pre and post-operative along the diagnosis, tennis elbow mean score was 74 and 33, in plica lesion mean score was 65 and 11, combined lesions mean score was 60 and 18 and cartilage lesion mean score was 60 and 20. Approaching chronic lateral elbow pain with arthroscopy can maintain the signficant improvement of functional result in midterm follow-up.

  3. A spore counting method and cell culture model for chlorine disinfection studies of Encephalitozoon syn. Septata intestinalis.

    PubMed

    Wolk, D M; Johnson, C H; Rice, E W; Marshall, M M; Grahn, K F; Plummer, C B; Sterling, C R

    2000-04-01

    The microsporidia have recently been recognized as a group of pathogens that have potential for waterborne transmission; however, little is known about the effects of routine disinfection on microsporidian spore viability. In this study, in vitro growth of Encephalitozoon syn. Septata intestinalis, a microsporidium found in the human gut, was used as a model to assess the effect of chlorine on the infectivity and viability of microsporidian spores. Spore inoculum concentrations were determined by using spectrophotometric measurements (percent transmittance at 625 nm) and by traditional hemacytometer counting. To determine quantitative dose-response data for spore infectivity, we optimized a rabbit kidney cell culture system in 24-well plates, which facilitated calculation of a 50% tissue culture infective dose (TCID(50)) and a minimal infective dose (MID) for E. intestinalis. The TCID(50) is a quantitative measure of infectivity and growth and is the number of organisms that must be present to infect 50% of the cell culture wells tested. The MID is as a measure of a system's permissiveness to infection and a measure of spore infectivity. A standardized MID and a standardized TCID(50) have not been reported previously for any microsporidian species. Both types of doses are reported in this paper, and the values were used to evaluate the effects of chlorine disinfection on the in vitro growth of microsporidia. Spores were treated with chlorine at concentrations of 0, 1, 2, 5, and 10 mg/liter. The exposure times ranged from 0 to 80 min at 25 degrees C and pH 7. MID data for E. intestinalis were compared before and after chlorine disinfection. A 3-log reduction (99.9% inhibition) in the E. intestinalis MID was observed at a chlorine concentration of 2 mg/liter after a minimum exposure time of 16 min. The log(10) reduction results based on percent transmittance-derived spore counts were equivalent to the results based on hemacytometer-derived spore counts. Our data

  4. A Spore Counting Method and Cell Culture Model for Chlorine Disinfection Studies of Encephalitozoon syn. Septata intestinalis

    PubMed Central

    Wolk, D. M.; Johnson, C. H.; Rice, E. W.; Marshall, M. M.; Grahn, K. F.; Plummer, C. B.; Sterling, C. R.

    2000-01-01

    The microsporidia have recently been recognized as a group of pathogens that have potential for waterborne transmission; however, little is known about the effects of routine disinfection on microsporidian spore viability. In this study, in vitro growth of Encephalitozoon syn. Septata intestinalis, a microsporidium found in the human gut, was used as a model to assess the effect of chlorine on the infectivity and viability of microsporidian spores. Spore inoculum concentrations were determined by using spectrophotometric measurements (percent transmittance at 625 nm) and by traditional hemacytometer counting. To determine quantitative dose-response data for spore infectivity, we optimized a rabbit kidney cell culture system in 24-well plates, which facilitated calculation of a 50% tissue culture infective dose (TCID50) and a minimal infective dose (MID) for E. intestinalis. The TCID50 is a quantitative measure of infectivity and growth and is the number of organisms that must be present to infect 50% of the cell culture wells tested. The MID is as a measure of a system's permissiveness to infection and a measure of spore infectivity. A standardized MID and a standardized TCID50 have not been reported previously for any microsporidian species. Both types of doses are reported in this paper, and the values were used to evaluate the effects of chlorine disinfection on the in vitro growth of microsporidia. Spores were treated with chlorine at concentrations of 0, 1, 2, 5, and 10 mg/liter. The exposure times ranged from 0 to 80 min at 25°C and pH 7. MID data for E. intestinalis were compared before and after chlorine disinfection. A 3-log reduction (99.9% inhibition) in the E. intestinalis MID was observed at a chlorine concentration of 2 mg/liter after a minimum exposure time of 16 min. The log10 reduction results based on percent transmittance-derived spore counts were equivalent to the results based on hemacytometer-derived spore counts. Our data suggest that

  5. Opposed Effects of Dityrosine Formation in Soluble and Aggregated α-Synuclein on Fibril Growth.

    PubMed

    Wördehoff, Michael M; Shaykhalishahi, Hamed; Groß, Luca; Gremer, Lothar; Stoldt, Matthias; Buell, Alexander K; Willbold, Dieter; Hoyer, Wolfgang

    2017-10-13

    Parkinson's disease is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY) crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from Parkinson's disease patients. Here we report that α-syn is highly susceptible to ultraviolet-induced DiY formation. We investigated DiY formation of α-syn and nine tyrosine-to-alanine mutants and monitored its effect on α-syn fibril formation in vitro. Ultraviolet irradiation of intrinsically disordered α-syn generates DiY-modified monomers and dimers, which inhibit fibril formation of unmodified α-syn by interfering with fibril elongation. The inhibition depends on both the DiY group and its integration into α-syn. When preformed α-syn fibrils are crosslinked by DiY formation, they gain increased resistance to denaturation. DiY-stabilized α-syn fibrils retain their high seeding efficiency even after being exposed to denaturant concentrations that completely depolymerize non-crosslinked seeds. Oxidative stress-associated DiY crosslinking of α-syn therefore entails two opposing effects: (i) inhibition of aggregation by DiY-modified monomers and dimers, and (ii) stabilization of fibrillar aggregates against potential degradation mechanisms, which can lead to promotion of aggregation, especially in the presence of secondary nucleation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. Turn-Directed α-β Conformational Transition of α-syn12 Peptide at Different pH Revealed by Unbiased Molecular Dynamics Simulations

    PubMed Central

    Liu, Lei; Cao, Zanxia

    2013-01-01

    The transition from α-helical to β-hairpin conformations of α-syn12 peptide is characterized here using long timescale, unbiased molecular dynamics (MD) simulations in explicit solvent models at physiological and acidic pH values. Four independent normal MD trajectories, each 2500 ns, are performed at 300 K using the GROMOS 43A1 force field and SPC water model. The most clustered structures at both pH values are β-hairpin but with different turns and hydrogen bonds. Turn9-6 and four hydrogen bonds (HB9-6, HB6-9, HB11-4 and HB4-11) are formed at physiological pH; turn8-5 and five hydrogen bonds (HB8-5, HB5-8, HB10-3, HB3-10 and HB12-1) are formed at acidic pH. A common folding mechanism is observed: the formation of the turn is always before the formation of the hydrogen bonds, which means the turn is always found to be the major determinant in initiating the transition process. Furthermore, two transition paths are observed at physiological pH. One of the transition paths tends to form the most-clustered turn and improper hydrogen bonds at the beginning, and then form the most-clustered hydrogen bonds. Another transition path tends to form the most-clustered turn, and turn5-2 firstly, followed by the formation of part hydrogen bonds, then turn5-2 is extended and more hydrogen bonds are formed. The transition path at acidic pH is as the same as the first path described at physiological pH. PMID:23708094

  7. Mutual exacerbation of peroxisome proliferator-activated receptor γ coactivator 1α deregulation and α-synuclein oligomerization.

    PubMed

    Eschbach, Judith; von Einem, Björn; Müller, Kathrin; Bayer, Hanna; Scheffold, Annika; Morrison, Bradley E; Rudolph, K Lenhard; Thal, Dietmar R; Witting, Anke; Weydt, Patrick; Otto, Markus; Fauler, Michael; Liss, Birgit; McLean, Pamela J; Spada, Albert R La; Ludolph, Albert C; Weishaupt, Jochen H; Danzer, Karin M

    2015-01-01

    Aggregation of α-synuclein (α-syn) and α-syn cytotoxicity are hallmarks of sporadic and familial Parkinson disease (PD), with accumulating evidence that prefibrillar oligomers and protofibrils are the pathogenic species in PD and related synucleinopathies. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a key regulator of mitochondrial biogenesis and cellular energy metabolism, has recently been associated with the pathophysiology of PD. Despite extensive effort on studying the function of PGC-1α in mitochondria, no studies have addressed whether PGC-1α directly influences oligomerization of α-syn or whether α-syn oligomers impact PGC-1α expression. We tested whether pharmacological or genetic activation of PGC-1α or PGC-11α knockdown could modulate the oligomerization of α-syn in vitro by using an α-syn -fragment complementation assay. In this study, we found that both PGC-1α reference gene (RG-PGC-1α) and the central nervous system (CNS)-specific PGC-1α (CNS-PGC-1α) are downregulated in human PD brain, in A30P α-syn transgenic animals, and in a cell culture model for α-syn oligomerization. Importantly, downregulation of both RG-PGC-1α and CNS-PGC-1α in cell culture or neurons from RG-PGC-1α-deficient mice leads to a strong induction of α-syn oligomerization and toxicity. In contrast, pharmacological activation or genetic overexpression of RG-PGC-1α reduced α-syn oligomerization and rescued α-syn-mediated toxicity. Based on our results, we propose that PGC-1α downregulation and α-syn oligomerization form a vicious circle, thereby influencing and/or potentiating each other. Our data indicate that restoration of PGC-1α is a promising approach for development of effective drugs for the treatment of PD and related synucleinopathies. © 2014 American Neurological Association.

  8. Dissecting the Molecular Pathway Involved in PLK2 Kinase-mediated α-Synuclein-selective Autophagic Degradation.

    PubMed

    Dahmene, Manel; Bérard, Morgan; Oueslati, Abid

    2017-03-03

    Increasing lines of evidence support the causal link between α-synuclein (α-syn) accumulation in the brain and Parkinson's disease (PD) pathogenesis. Therefore, lowering α-syn protein levels may represent a viable therapeutic strategy for the treatment of PD and related disorders. We recently described a novel selective α-syn degradation pathway, catalyzed by the activity of the Polo-like kinase 2 (PLK2), capable of reducing α-syn protein expression and suppressing its toxicity in vivo However, the exact molecular mechanisms underlying this degradation route remain elusive. In the present study we report that among PLK family members, PLK3 is also able to catalyze α-syn phosphorylation and degradation in living cells. Using pharmacological and genetic approaches, we confirmed the implication of the macroautophagy on PLK2-mediated α-syn turnover, and our observations suggest a concomitant co-degradation of these two proteins. Moreover, we showed that the N-terminal region of α-syn is important for PLK2-mediated α-syn phosphorylation and degradation and is implicated in the physical interaction between the two proteins. We also demonstrated that PLK2 polyubiquitination is important for PLK2·α-syn protein complex degradation, and we hypothesize that this post-translational modification may act as a signal for the selective recognition by the macroautophagy machinery. Finally, we observed that the PD-linked mutation E46K enhances PLK2-mediated α-syn degradation, suggesting that this mutated form is a bona fide substrate of this degradation pathway. In conclusion, our study provides a detailed description of the new degradation route of α-syn and offers new opportunities for the development of therapeutic strategies aiming to reduce α-syn protein accumulation and toxicity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

    PubMed Central

    Masliah, Eliezer; Rockenstein, Edward; Mante, Michael; Crews, Leslie; Spencer, Brian; Adame, Anthony; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Rohn, Troy T.; Mueller-Steiner, Sarah; Seubert, Peter; Barbour, Robin; McConlogue, Lisa; Buttini, Manuel; Games, Dora; Schenk, Dale

    2011-01-01

    Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB. PMID:21559417

  10. Drug Targets from Genetics: Alpha-Synuclein

    PubMed Central

    Danzer, Karin M.; McLean, Pamela J.

    2012-01-01

    One of the critical issues in Parkinson disease (PD) research is the identity of the specific toxic, pathogenic moiety. In PD, mutations in alpha-synuclein (αsyn) or multiplication of the SNCA gene encoding αsyn, result in a phenotype of cellular inclusions, cell death, and brain dysfunction. While the historical point of view has been that the macroscopic aggregates containing αsyn are the toxic species, in the last several years evidence has emerged that suggests instead that smaller soluble species - likely oligomers containing misfolded αsyn - are actually the toxic moiety and that the fibrillar inclusions may even be a cellular detoxification pathway and less harmful. If soluble misfolded species of αsyn are the toxic moieties, then cellular mechanisms that degrade misfolded αsyn would be neuroprotective and a rational target for drug development. In this review we will discuss the fundamental mechanisms underlying αsyn toxicity including oligomer formation, oxidative stress, and degradation pathways and consider rational therapeutic strategies that may have the potential to prevent or halt αsyn induced pathogenesis in PD. PMID:21838671

  11. Silencing Alpha Synuclein in Mature Nigral Neurons Results in Rapid Neuroinflammation and Subsequent Toxicity

    PubMed Central

    Benskey, Matthew J.; Sellnow, Rhyomi C.; Sandoval, Ivette M.; Sortwell, Caryl E.; Lipton, Jack W.; Manfredsson, Fredric P.

    2018-01-01

    Human studies and preclinical models of Parkinson’s disease implicate the involvement of both the innate and adaptive immune systems in disease progression. Further, pro-inflammatory markers are highly enriched near neurons containing pathological forms of alpha synuclein (α-syn), and α-syn overexpression recapitulates neuroinflammatory changes in models of Parkinson’s disease. These data suggest that α-syn may initiate a pathological inflammatory response, however the mechanism by which α-syn initiates neuroinflammation is poorly understood. Silencing endogenous α-syn results in a similar pattern of nigral degeneration observed following α-syn overexpression. Here we aimed to test the hypothesis that loss of α-syn function within nigrostriatal neurons results in neuronal dysfunction, which subsequently stimulates neuroinflammation. Adeno-associated virus (AAV) expressing an short hairpin RNA (shRNA) targeting endogenous α-syn was unilaterally injected into the substantia nigra pars compacta (SNc) of adult rats, after which nigrostriatal pathology and indices of neuroinflammation were examined at 7, 10, 14 and 21 days post-surgery. Removing endogenous α-syn from nigrostriatal neurons resulted in a rapid up-regulation of the major histocompatibility complex class 1 (MHC-1) within transduced nigral neurons. Nigral MHC-1 expression occurred prior to any overt cell death and coincided with the recruitment of reactive microglia and T-cells to affected neurons. Following the induction of neuroinflammation, α-syn knockdown resulted in a 50% loss of nigrostriatal neurons in the SNc and a corresponding loss of nigrostriatal terminals and dopamine (DA) concentrations within the striatum. Expression of a control shRNA did not elicit any pathological changes. Silencing α-syn within glutamatergic neurons of the cerebellum did not elicit inflammation or cell death, suggesting that toxicity initiated by α-syn silencing is specific to DA neurons. These data provide

  12. Cellular response of human neuroblastoma cells to α-synuclein fibrils, the main constituent of Lewy bodies.

    PubMed

    Pieri, Laura; Chafey, Philippe; Le Gall, Morgane; Clary, Guilhem; Melki, Ronald; Redeker, Virginie

    2016-01-01

    α-Synuclein (α-Syn) fibrils are the main constituent of Lewy bodies and a neuropathological hallmark of Parkinson's disease (PD). The propagation of α-Syn assemblies from cell to cell suggests that they are involved in PD progression. We previously showed that α-Syn fibrils are toxic because of their ability to bind and permeabilize cell membranes. Here, we document the cellular response in terms of proteome changes of SH-SY5Y cells exposed to exogenous α-Syn fibrils. We compare the proteomes of cells of neuronal origin exposed or not either to oligomeric or fibrillar α-Syn using two dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry. Only α-Syn fibrils induce significant changes in the proteome of SH-SY5Y cells. In addition to proteins associated to apoptosis and toxicity, or proteins previously linked to neurodegenerative diseases, we report an overexpression of proteins involved in intracellular vesicle trafficking. We also report a remarkable increase in fibrillar α-Syn heterogeneity, mainly due to C-terminal truncations. Our results show that cells of neuronal origin adapt their proteome to exogenous α-Syn fibrils and actively modify those assemblies. Cells of neuronal origin adapt their proteome to exogenous toxic α-Syn fibrils and actively modify those assemblies. Our results bring insights into the cellular response and clearance events the cells implement to face the propagation of α-Syn assemblies associated to pathology.

  13. Studies of protein aggregation in A53T α-synuclein transgenic, Tg2576 transgenic, and P246L presenilin-1 knock-in cross bred mice.

    PubMed

    Emmer, Kristel L; Covy, Jason P; Giasson, Benoit I

    2012-01-24

    Synucleinopathies are a group of neurodegenerative disorders, including Parkinson disease, associated with neuronal amyloid inclusions comprised of the presynaptic protein α-synuclein (α-syn); however the biological events that initiate and lead to the formation of these inclusions are still poorly understood. There is mounting evidence that intracellular α-syn aggregation may proceed via a seeding mechanism and could spread between neurons through a prion-like mechanism that may involve other amyloidogenic proteins. Several lines of evidence suggest that Aβ peptides and/or extracellular Aβ deposits may directly or indirectly promote intracellular α-syn aggregation. To assess the effects of Aβ peptides and extracellular Aβ deposits on α-syn aggregate formation, transgenic mice (line M83) expressing A53T human α-syn that are sensitive to developing α-syn pathological inclusions were cross bred to Tg2576 transgenic mice that generated elevated levels of Aβ peptides and develop abundant Aβ plaques. In addition these mice were bred to mice with the P264L presenilin-1 knock-in mutation that further promotes Aβ plaque formation. These mice demonstrated the expected formation of Aβ plaques; however despite the accumulation of hyperphosphorylated α-syn dystrophic neurites within or surrounding Aβ plaques, no additional α-syn pathologies were observed. These studies show that Aβ amyloid deposits can cause the local aggregation of α-syn, but these did not lead to more extensive α-syn pathology. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Novel stereocontrolled approach to syn- and anti-oxepene-cyclogeranyl trans-fused polycyclic systems: asymmetric total synthesis of (-)-Aplysistatin, (+)-Palisadin A, (+)-Palisadin B, (+)-12-hydroxy-palisadin B, and the AB ring system of adociasulfate-2 and toxicol A.

    PubMed

    Couladouros, Elias A; Vidali, Veroniki P

    2004-08-06

    A new stereocontrolled method for the formation of trans-anti cyclogeranyl-oxepene systems is described. The demanding stereochemistry is secured by stereoselective coupling of a cyclogeranyl tertiary alcohol with a 1,2-unsymmetrically substituted epoxide, while the formation of the highly strained oxepene is achieved employing ring-closing metathesis. Since the stereochemistry of the trans-fused 6,7-ring system is determined by the epoxide, the method also allows the construction of trans-syn 6,7-ring systems. This approach leads to the synthesis of the AB fragment of Adociasulfate-2 and Toxicol A, for the first time. The flexibility and efficiency of the presented strategy is demonstrated by the total asymmetric synthesis of (-)-Aplysistatin, (+)-Palisadin A, (+)-12-hydroxy-Palisadin B, and (+)-Palisadin B, employing two similar key intermediates.

  15. Hippocampal neuronal cells that accumulate α-synuclein fragments are more vulnerable to Aβ oligomer toxicity via mGluR5 – implications for dementia with Lewy bodies

    PubMed Central

    2014-01-01

    Background In dementia with Lewy bodies (DLB) abnormal interactions between α-synuclein (α-syn) and beta amyloid (Aβ) result in selective degeneration of neurons in the neocortex, limbic system and striatum. However, factors rendering these neurons selectively vulnerable have not been fully investigated. The metabotropic glutamate receptor 5 (mGluR5) has been shown to be up regulated in DLB and might play a role as a mediator of the neurotoxic effects of Aβ and α-syn in vulnerable neuronal populations. In this context, the main objective of the present study was to investigate the role of mGluR5 as a mediator of the neurotoxic effects of α-syn and Aβ in the hippocampus. Results We generated double transgenic mice over-expressing amyloid precursor protein (APP) and α-syn under the mThy1 cassette and investigated the relationship between α-syn cleavage, Aβ, mGluR5 and neurodegeneration in the hippocampus. We found that compared to the single tg mice, the α-syn/APP tg mice displayed greater accumulation of α-syn and mGluR5 in the CA3 region of the hippocampus compared to the CA1 and other regions. This was accompanied by loss of CA3 (but not CA1) neurons in the single and α-syn/APP tg mice and greater loss of MAP 2 and synaptophysin in the CA3 in the α-syn/APP tg. mGluR5 gene transfer using a lentiviral vector into the hippocampus CA1 region resulted in greater α-syn accumulation and neurodegeneration in the single and α-syn/APP tg mice. In contrast, silencing mGluR5 with a lenti-shRNA protected neurons in the CA3 region of tg mice. In vitro, greater toxicity was observed in primary hippocampal neuronal cultures treated with Aβ oligomers and over-expressing α-syn; this effect was attenuated by down-regulating mGluR5 with an shRNA lentiviral vector. In α-syn-expressing neuronal cells lines, Aβ oligomers promoted increased intracellular calcium levels, calpain activation and α-syn cleavage resulting in caspase-3-dependent cell death. Treatment with

  16. Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage.

    PubMed

    Paiva, Isabel; Pinho, Raquel; Pavlou, Maria Angeliki; Hennion, Magali; Wales, Pauline; Schütz, Anna-Lena; Rajput, Ashish; Szego, Éva M; Kerimoglu, Cemil; Gerhardt, Ellen; Rego, Ana Cristina; Fischer, André; Bonn, Stefan; Outeiro, Tiago F

    2017-06-15

    Alpha-synuclein (aSyn) is considered a major culprit in Parkinson's disease (PD) pathophysiology. However, the precise molecular function of the protein remains elusive. Recent evidence suggests that aSyn may play a role on transcription regulation, possibly by modulating the acetylation status of histones. Our study aimed at evaluating the impact of wild-type (WT) and mutant A30P aSyn on gene expression, in a dopaminergic neuronal cell model, and decipher potential mechanisms underlying aSyn-mediated transcriptional deregulation. We performed gene expression analysis using RNA-sequencing in Lund Human Mesencephalic (LUHMES) cells expressing endogenous (control) or increased levels of WT or A30P aSyn. Compared to control cells, cells expressing both aSyn variants exhibited robust changes in the expression of several genes, including downregulation of major genes involved in DNA repair. WT aSyn, unlike A30P aSyn, promoted DNA damage and increased levels of phosphorylated p53. In dopaminergic neuronal cells, increased aSyn expression led to reduced levels of acetylated histone 3. Importantly, treatment with sodium butyrate, a histone deacetylase inhibitor (HDACi), rescued WT aSyn-induced DNA damage, possibly via upregulation of genes involved in DNA repair. Overall, our findings provide novel and compelling insight into the mechanisms associated with aSyn neurotoxicity in dopaminergic cells, which could be ameliorated with an HDACi. Future studies will be crucial to further validate these findings and to define novel possible targets for intervention in PD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Leptotrombidium (Acari: Trombiculidae) of the World.

    PubMed

    Stekolnikov, Alexandr A

    2013-01-01

    The chigger mite genus Leptotrombidium Nagayo, Miyagawa, Mitamura and Imamura, 1916 is reviewed using literature data. For 340 larval species brief diagnoses, synonymy, data on type hosts and type localities are provided. The genus is divided into species-groups based on morphological evidence enabling easier establishment of group-membership of un-known specimens in the future. Some species groups are supported by a hierarchical cluster analysis with multiscale boot-strap resampling applied to a matrix including 335 species and geographic morphotypes and 19 standard quantitative characters. Six new species from mammalian hosts are described: L. aenigmami sp. nov., L. abramovi sp. nov., L. tikhon-ovi sp. nov., L. bochkovi sp. nov., L. laoense sp. nov., and L. megaloti sp. nov. from Laos. Seven names created by Ver-cammen-Grandjean and Langston (1976) for infrasubspecific entities are applied to species with the same descriptions: Leptotrombidium tenompaki sp. nov., L. kinabalui sp. nov., L. megabodense sp. nov., L. minului sp. nov., L. ului sp. nov., L. megalangati sp. nov., and L. saigoni sp. nov. A new replacement name is proposed: L. ushi nom. nov. pro L. hsui Wu, Yang and Li, 1999 (praeocc. Yu, Yang and Gong, 1986). Nineteen new synonyms and 7 new combinations are proposed: Leptotrombidium (= Hsuella Wang, Li and Shi, 1989, syn. nov.; = Leptotrombidium (Monosigmum) Wen, 2001, syn. nov.), L. deliense (Walch, 1922) (= L. deliense sinense Wen and Chen, 1984, syn. nov.; = L. deliense microsetosa Zhao, Tang and Mo, 1986, syn. nov.), L. sialkotense Vercammen-Grandjean and Langston, 1976 (= L. jishoum Wen, Li, Zhang and Liao, 1988, syn. nov.), L. imphalum Vercammen-Grandjean and Langston, 1976 (= L. imphalum sabahense Vercam-men-Grandjean and Langston, 1976, syn. nov.; = L. chiangraiensis Tanskul and Linthicum, 1997, syn. nov.), L. wenense Wu, Wen, Yang and Wu, 1982 (= L. kaohuense Li, Wang and Chen, 1997, syn. nov.), L. longimedian Brown, 1992 (= L. mindanensis Brown

  18. Synthetic biology: a utilitarian perspective.

    PubMed

    Smith, Kevin

    2013-10-01

    I examine the positive and negative features of synthetic biology ('SynBio') from a utilitarian ethical perspective. The potential beneficial outcomes from SynBio in the context of medicine are substantial; however it is not presently possible to predict precise outcomes due to the nascent state of the field. Potential negative outcomes from SynBio also exist, including iatrogenesis and bioterrorism; however it is not yet possible to quantify these risks. I argue that the application of a 'precautionary' approach to SynBio is ethically fraught, as is the notion that SynBio-associated knowledge ought to be restricted. I conclude that utilitarians ought to support a broadly laissez-faire stance in respect of SynBio. © 2013 John Wiley & Sons Ltd.

  19. [Imaging of the elbow joint with focus MRI. Part 2: muscles, nerves and synovial membranes].

    PubMed

    Rehm, J; Zeifang, F; Weber, M-A

    2014-03-01

    This review article discusses the magnetic resonance imaging (MRI) features and pathological changes of muscles, nerves and the synovial lining of the elbow joint. Typical imaging findings are illustrated and discussed. In addition, the cross-sectional anatomy and anatomical variants, such as accessory muscles and plicae are discussed. Injuries of the muscles surrounding the elbow joint, as well as chronic irritation are particularly common in athletes. Morphological changes in MRI, for example tennis or golfer's elbow are typical and often groundbreaking. By adapting the examination sequences, imaging planes and slices, complete and incomplete tendon ruptures can be reliably diagnosed. Although the clinical and electrophysiological examinations form the basis for the diagnosis of peripheral neuropathies, MRI provides useful additional information about the precise localization due to its high resolution and good soft tissue contrast and helps to rule out differential diagnoses. Synovial diseases, such as inflammatory arthritis, proliferative diseases and also impinging plicae must be considered in the MRI diagnostics of the elbow joint.

  20. Syn-convergence extension in the southern Lhasa terrane: Evidence from late Cretaceous adakitic granodiorite and coeval gabbroic-dioritic dykes

    NASA Astrophysics Data System (ADS)

    Ma, Xuxuan; Xu, Zhiqin; Meert, Joseph G.

    2017-10-01

    Late Cretaceous (∼100-80 Ma) magmatism in the Gangdese magmatic belt plays a pivotal role in understanding the evolutionary history and tectonic regime of the southern Lhasa terrane. The geodynamic process for the formation of the early Late Cretaceous magmatism has long been an issue of hot debates. Here, petrology, geochronology and geochemistry of early Late Cretaceous granodiorite and coeval gabbroic-dioritic dykes in the Caina region, southern Lhasa, were investigated in an effort to ascertain their petrogenesis, age of intrusion, magma mixing and tectonic setting. Zircon U-Pb dating of granodiorite yields 206Pb/238U ages of 85.8 ± 1.7 and 86.4 ± 1.1 Ma, whilst that of the E-W trending dykes yields ages of 82.7 ± 2.6 and 83.5 ± 3.5 Ma. Within error, the crystallization ages of the dykes and the granodiorite are indistinguishable. Field observations and mineralogical microstructures are suggestive of a magma mixing process during the formation of the dykes and the granodiorite. The granodiorite exhibits geochemical features that are in agreement with those of subduction-related high-SiO2 adakites. The granodiorite and dykes have relatively constant εNd(t) values of +2.2 to +4.9 and initial 87Sr/86Sr ratios (0.7045-0.7047). These similar characteristics are herein interpreted as an evolutionary series from the dykes to granodiorite, consistent with magma mixing process. Ti-in-zircon thermometer and Al-in-hornblende barometer indicate that the granodiorite and the dioritic dyke crystallized at temperatures of ca. 750 and 800 °C, depths of ca. 6-10 and 5-9 km, respectively. Taking into account the synchronous magmatic rocks in the Gangdese Belt and the coeval rifted basin within the Lhasa terrane, the granodiorite and dykes reveal an early Late Cretaceous syn-convergence extensional regime in the southern Lhasa terrane, triggered by slab rollback of the Neotethyan oceanic lithosphere.

  1. Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking

    PubMed Central

    Choi, Bong-Kyu; Choi, Mal-Gi; Kim, Jae-Yeol; Yang, Yoosoo; Lai, Ying; Kweon, Dae-Hyuk; Lee, Nam Ki; Shin, Yeon-Kyun

    2013-01-01

    Parkinson disease and dementia with Lewy bodies are featured with the formation of Lewy bodies composed mostly of α-synuclein (α-Syn) in the brain. Although evidence indicates that the large oligomeric or protofibril forms of α-Syn are neurotoxic agents, the detailed mechanisms of the toxic functions of the oligomers remain unclear. Here, we show that large α-Syn oligomers efficiently inhibit neuronal SNARE-mediated vesicle lipid mixing. Large α-Syn oligomers preferentially bind to the N-terminal domain of a vesicular SNARE protein, synaptobrevin-2, which blocks SNARE-mediated lipid mixing by preventing SNARE complex formation. In sharp contrast, the α-Syn monomer has a negligible effect on lipid mixing even with a 30-fold excess compared with the case of large α-Syn oligomers. Thus, the results suggest that large α-Syn oligomers function as inhibitors of dopamine release, which thus provides a clue, at the molecular level, to their neurotoxicity. PMID:23431141

  2. Sequestration of synaptic proteins by alpha-synuclein aggregates leading to neurotoxicity is inhibited by small peptide

    PubMed Central

    Choi, Mal-Gi; Kim, Mi Jin; Kim, Do-Geun; Yu, Ri; Jang, You-Na

    2018-01-01

    α-Synuclein (α-syn) is a major component of Lewy bodies found in synucleinopathies including Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Under the pathological conditions, α-syn tends to generate a diverse form of aggregates showing toxicity to neuronal cells and able to transmit across cells. However, mechanisms by which α-syn aggregates affect cytotoxicity in neurons have not been fully elucidated. Here we report that α-syn aggregates preferentially sequester specific synaptic proteins such as vesicle-associated membrane protein 2 (VAMP2) and synaptosomal-associated protein 25 (SNAP25) through direct binding which is resistant to SDS. The sequestration effect of α-syn aggregates was shown in a cell-free system, cultured primary neurons, and PD mouse model. Furthermore, we identified a specific blocking peptide derived from VAMP2 which partially inhibited the sequestration by α-syn aggregates and contributed to reduced neurotoxicity. These results provide a mechanism of neurotoxicity mediated by α-syn aggregates and suggest that the blocking peptide interfering with the pathological role of α-syn aggregates could be useful for designing a potential therapeutic drug for the treatment of PD. PMID:29608598

  3. MicroRNA-7 facilitates the degradation of alpha-synuclein and its aggregates by promoting autophagy.

    PubMed

    Choi, Doo Chul; Yoo, Myungsik; Kabaria, Savan; Junn, Eunsung

    2018-05-05

    Alpha-Synuclein (α-Syn) is an important protein in the pathogenesis of Parkinson disease (PD) as it accumulates as fibrillar inclusions in affected brain regions including dopaminergic neurons in the substantia nigra. Elevated levels of α-Syn seem to be crucial in mediating its toxicity. Thus, detailed information regarding the regulatory mechanism of α-Syn expression in several layers such as transcription, post-transcription and post-translation is needed in order to devise therapeutic interventions for PD. Previously, we reported that expression of α-Syn is repressed by microRNA-7 (miR-7) through its effect on the 3'-untranslated region (UTR) of α-Syn mRNA. Here, we show that miR-7 also accelerates the clearance of α-Syn and its aggregates by promoting autophagy in differentiated ReNcell VM cells. Further, miR-7 facilitates the degradation of pre-formed fibrils of α-Syn transported from outside the cells. This additional mechanism for reducing α-Syn levels show miR-7 to be an important molecular target for PD and other alpha-synucleinopathies. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. α-Synuclein interferes with the ESCRT-III complex contributing to the pathogenesis of Lewy body disease.

    PubMed

    Spencer, Brian; Kim, Changyoun; Gonzalez, Tania; Bisquertt, Alejandro; Patrick, Christina; Rockenstein, Edward; Adame, Anthony; Lee, Seung-Jae; Desplats, Paula; Masliah, Eliezer

    2016-03-15

    α-Synuclein (α-syn) has been implicated in neurological disorders with parkinsonism, including Parkinson's disease and Dementia with Lewy body. Recent studies have shown α-syn oligomers released from neurons can propagate from cell-to-cell in a prion-like fashion exacerbating neurodegeneration. In this study, we examined the role of the endosomal sorting complex required for transport (ESCRT) pathway on the propagation of α-syn. α-syn, which is transported via the ESCRT pathway through multivesicular bodies for degradation, can also target the degradation of the ESCRT protein-charged multivesicular body protein (CHMP2B), thus generating a roadblock of endocytosed α-syn. Disruption of the ESCRT transport system also resulted in increased exocytosis of α-syn thus potentially increasing cell-to-cell propagation of synuclein. Conversely, delivery of a lentiviral vector overexpressing CHMP2B rescued the neurodegeneration in α-syn transgenic mice. Better understanding of the mechanisms of intracellular trafficking of α-syn might be important for understanding the pathogenesis and developing new treatments for synucleinopathies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Synapsins Are Downstream Players of the BDNF-Mediated Axonal Growth.

    PubMed

    Marte, Antonella; Messa, Mirko; Benfenati, Fabio; Onofri, Franco

    2017-01-01

    Synapsins (Syns) are synaptic vesicle-associated phosphoproteins involved in neuronal development and neurotransmitter release. While Syns are implicated in the regulation of brain-derived neurotrophic factor (BDNF)-induced neurotransmitter release, their role in the BDNF developmental effects has not been fully elucidated. By using primary cortical neurons from Syn I knockout (KO) and Syn I/II/III KO mice, we studied the effects of BDNF and nerve growth factor (NGF) on axonal growth. While NGF had similar effects in all genotypes, BDNF induced significant differences in Syn KO axonal outgrowth compared to wild type (WT), an effect that was rescued by the re-expression of Syn I. Moreover, the significant increase of axonal branching induced by BDNF in WT neurons was not detectable in Syn KO neurons. The expression analysis of BDNF receptors in Syn KO neurons revealed a significant decrease of the full length TrkB receptor and an increase in the levels of the truncated TrkB.t1 isoform and p75 NTR associated with a marked reduction of the BDNF-induced MAPK/Erk activation. By using the Trk inhibitor K252a, we demonstrated that these differences in BDNF effects were dependent on a TrkB/p75 NTR imbalance. The data indicate that Syn I plays a pivotal role in the BDNF signal transduction during axonal growth.

  6. Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity.

    PubMed

    Villar-Piqué, Anna; Lopes da Fonseca, Tomás; Sant'Anna, Ricardo; Szegö, Éva Mónika; Fonseca-Ornelas, Luis; Pinho, Raquel; Carija, Anita; Gerhardt, Ellen; Masaracchia, Caterina; Abad Gonzalez, Enrique; Rossetti, Giulia; Carloni, Paolo; Fernández, Claudio O; Foguel, Debora; Milosevic, Ira; Zweckstetter, Markus; Ventura, Salvador; Outeiro, Tiago Fleming

    2016-10-18

    Synucleinopathies are a group of progressive disorders characterized by the abnormal aggregation and accumulation of α-synuclein (aSyn), an abundant neuronal protein that can adopt different conformations and biological properties. Recently, aSyn pathology was shown to spread between neurons in a prion-like manner. Proteins like aSyn that exhibit self-propagating capacity appear to be able to adopt different stable conformational states, known as protein strains, which can be modulated both by environmental and by protein-intrinsic factors. Here, we analyzed these factors and found that the unique combination of the neurodegeneration-related metal copper and the pathological H50Q aSyn mutation induces a significant alteration in the aggregation properties of aSyn. We compared the aggregation of WT and H50Q aSyn with and without copper, and assessed the effects of the resultant protein species when applied to primary neuronal cultures. The presence of copper induces the formation of structurally different and less-damaging aSyn aggregates. Interestingly, these aggregates exhibit a stronger capacity to induce aSyn inclusion formation in recipient cells, which demonstrates that the structural features of aSyn species determine their effect in neuronal cells and supports a lack of correlation between toxicity and inclusion formation. In total, our study provides strong support in favor of the hypothesis that protein aggregation is not a primary cause of cytotoxicity.

  7. Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body myositis, regenerating and necrotic muscle fibers, and at neuromuscular junctions.

    PubMed

    Askanas, V; Engel, W K; Alvarez, R B; McFerrin, J; Broccolini, A

    2000-07-01

    Alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older patients. Its muscle phenotype shows several similarities with Alzheimer disease brain. A distinct feature of s-IBM pathology is specific vacuolar degeneration of muscle fibers characterized by intracellular amyloid inclusions formed by both amyloid-beta (Abeta) and paired-helical filaments composed of phosphorylated tau. We immunostained alpha-syn in muscle biopsies of s-IBM, disease-control, and normal patients. Approximately 60% of Abeta-positive vacuolated muscle fibers (VMF) contained well-defined inclusions immunoreactive with antibodies against alpha-syn. In those fibers. alpha-syn co-localized with Abeta, both by light microscopy, and ultrastructurally. Paired-helical filaments did not contain alpha-syn immunoreactivity. In all muscle biopsies, alpha-syn was strongly immunoreactive at the postsynaptic region of the neuromuscular junctions. alpha-syn immunoreactivity also occurred diffusely in regenerating and necrotic muscle fibers. In cultured human muscle fibers, alpha-syn and its mRNA were expressed by immunocytochemistry, immunoblots, and Northern blots. Our study provides the first demonstration that alpha-syn participates in normal and pathologic processes of human muscle. Therefore. its function is not exclusive to the brain and neurodegenerative diseases.

  8. Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays

    PubMed Central

    Lek, Sovanarak; Vargas-Medrano, Javier; Villanueva, Ernesto; Marcus, Brian; Godfrey, Wesley; Perez, Ruth G.

    2017-01-01

    α-Synuclein (aSyn), β-Synuclein (bSyn), and γ-Synuclein (gSyn) are members of a conserved family of chaperone-like proteins that are highly expressed in vertebrate neuronal tissues. Of the three synucleins, only aSyn has been strongly implicated in neurodegenerative disorders such as Parkinson's disease, Dementia with Lewy Bodies, and Multiple System Atrophy. In studying normal aSyn function, data indicate that aSyn stimulates the activity of the catalytic subunit of an abundantly expressed dephosphorylating enzyme, PP2Ac in vitro and in vivo. Prior data show that aSyn aggregation in human brain reduces PP2Ac activity in regions with Lewy body pathology, where soluble aSyn has become insoluble. However, because all three synucleins have considerable homology in the amino acid sequences, experiments were designed to test if all can modulate PP2Ac activity. Using recombinant synucleins and recombinant PP2Ac protein, activity was assessed by malachite green colorimetric assay. Data revealed that all three recombinant synucleins stimulated PP2Ac activity in cell-free assays, raising the possibility that the conserved homology between synucleins may endow all three homologs with the ability to bind to and activate the PP2Ac. Co-immunoprecipitation data, however, suggest that PP2Ac modulation likely occurs through endogenous interactions between aSyn and PP2Ac in vivo. PMID:28829427

  9. Best Practices for Generating and Using Alpha-Synuclein Pre-Formed Fibrils to Model Parkinson’s Disease in Rodents

    PubMed Central

    Polinski, Nicole K.; Volpicelli-Daley, Laura A.; Sortwell, Caryl E.; Luk, Kelvin C.; Cremades, Nunilo; Gottler, Lindsey M.; Froula, Jessica; Duffy, Megan F.; Lee, Virginia M.Y.; Martinez, Terina N.; Dave, Kuldip D.

    2018-01-01

    Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting approximately one-percent of the population over the age of sixty. Although many animal models have been developed to study this disease, each model presents its own advantages and caveats. A unique model has arisen to study the role of alpha-synuclein (aSyn) in the pathogenesis of PD. This model involves the conversion of recombinant monomeric aSyn protein to a fibrillar form—the aSyn pre-formed fibril (aSyn PFF)—which is then injected into the brain or introduced to the media in culture. Although many groups have successfully adopted and replicated the aSyn PFF model, issues with generating consistent pathology have been reported by investigators. To improve the replicability of this model and diminish these issues, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has enlisted the help of field leaders who performed key experiments to establish the aSyn PFF model to provide the research community with guidelines and practical tips for improving the robustness and success of this model. Specifically, we identify key pitfalls and suggestions for avoiding these mistakes as they relate to generating the aSyn PFFs from monomeric protein, validating the formation of pathogenic aSyn PFFs, and using the aSyn PFFs in vivo or in vitro to model PD. With this additional information, adoption and use of the aSyn PFF model should present fewer challenges, resulting in a robust and widely available model of PD. PMID:29400668

  10. α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease Severity

    PubMed Central

    Daniele, Simona; Frosini, Daniela; Pietrobono, Deborah; Petrozzi, Lucia; Lo Gerfo, Annalisa; Baldacci, Filippo; Fusi, Jonathan; Giacomelli, Chiara; Siciliano, Gabriele; Trincavelli, Maria Letizia; Franzoni, Ferdinando; Ceravolo, Roberto; Martini, Claudia; Bonuccelli, Ubaldo

    2018-01-01

    Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ1–42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (N = 28) of patients affected by Parkinson’s disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aβ1–42 and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aβ1–42 was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aβ1–42 and tau in peripheral tissues; interestingly, α-syn-Aβ1–42 concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aβ1–42 concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD. PMID:29520218

  11. Inoculation of α-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve.

    PubMed

    Uemura, Norihito; Yagi, Hisashi; Uemura, Maiko T; Hatanaka, Yusuke; Yamakado, Hodaka; Takahashi, Ryosuke

    2018-05-11

    Intraneuronal α-synuclein (α-Syn) aggregates known as Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the pathological hallmarks of Parkinson's disease (PD). Braak's hypothesis based on autopsy studies suggests that Lewy pathology initially occurs in the enteric nervous system (ENS) and then travels retrogradely to the dorsal motor nucleus of the vagus nerve (dmX), proceeding from there in a caudo-rostral direction. Recent evidence that α-Syn aggregates propagate between interconnected neurons supports this hypothesis. However, there is no direct evidence demonstrating this transmission from the ENS to the dmX and then to the SNpc. We inoculated α-Syn preformed fibrils (PFFs) or phosphate-buffered saline (PBS) into the mouse gastric wall and analyzed the progression of the pathology. The mice inoculated with α-Syn PFFs, but not with PBS, developed phosphorylated α-Syn (p-α-Syn)-positive LB-like aggregates in the dmX at 45 days postinoculation. This aggregate formation was completely abolished when vagotomy was performed prior to inoculation of α-Syn PFFs, suggesting that the aggregates in the dmX were retrogradely induced via the vagus nerve. Unexpectedly, the number of neurons containing p-α-Syn-positive aggregates in the dmX decreased over time, and no further caudo-rostral propagation beyond the dmX was observed up to 12 months postinoculation. P-α-Syn-positive aggregates were also present in the myenteric plexus at 12 months postinoculation. However, unlike in patients with PD, there was no cell-type specificity in neurons containing those aggregates in this model. These results indicate that α-Syn PFF inoculation into the mouse gastrointestinal tract can induce α-Syn pathology resembling that of very early PD, but other factors are apparently required if further progression of PD pathology is to be replicated in this animal model.

  12. A sensitive assay reveals structural requirements for α-synuclein fibril growth

    PubMed Central

    Tsai, Christina; Bagchi, Devika P.; Engel, Laura A.; Sarezky, Jonathan; Kotzbauer, Paul T.

    2017-01-01

    The accumulation of α-synuclein (α-syn) fibrils in neuronal inclusions is the defining pathological process in Parkinson's disease (PD). A pathogenic role for α-syn fibril accumulation is supported by the identification of dominantly inherited α-syn (SNCA) gene mutations in rare cases of familial PD. Fibril formation involves a spontaneous nucleation event in which soluble α-syn monomers associate to form seeds, followed by fibril growth during which monomeric α-syn molecules sequentially associate with existing seeds. To better investigate this process, we developed sensitive assays that use the fluorescein arsenical dye FlAsH (fluorescein arsenical hairpin binder) to detect soluble oligomers and mature fibrils formed from recombinant α-syn protein containing an N-terminal bicysteine tag (C2-α-syn). Using seed growth by monomer association (SeGMA) assays to measure fibril growth over 3 h in the presence of C2-α-syn monomer, we observed that some familial PD-associated α-syn mutations (i.e. H50Q and A53T) greatly increased growth rates, whereas others (E46K, A30P, and G51D) decreased growth rates. Experiments with wild-type seeds extended by mutant monomer and vice versa revealed that single-amino acid differences between seed and monomer proteins consistently decreased growth rates. These results demonstrate that α-syn monomer association during fibril growth is a highly ordered process that can be disrupted by misalignment of individual amino acids and that only a subset of familial-PD mutations causes fibril accumulation through increased fibril growth rates. The SeGMA assays reported herein can be utilized to further elucidate structural requirements of α-syn fibril growth and to identify growth inhibitors as a potential therapeutic approach in PD. PMID:28373279

  13. Syntaxin-4 mediates exocytosis of pre-docked and newcomer insulin granules underlying biphasic glucose-stimulated insulin secretion in human pancreatic beta cells.

    PubMed

    Xie, Li; Zhu, Dan; Dolai, Subhankar; Liang, Tao; Qin, Tairan; Kang, Youhou; Xie, Huanli; Huang, Ya-Chi; Gaisano, Herbert Y

    2015-06-01

    Of the four exocytotic syntaxins (Syns), much is now known about the role of Syn-1A (pre-docked secretory granules [SGs]) and Syn-3 (newcomer SGs) in insulin exocytosis. Some work was reported on Syn-4's role in biphasic glucose-stimulated insulin secretion (GSIS), but its precise role in insulin SG exocytosis remains unclear. In this paper we examine this role in human beta cells. Endogenous function of Syn-4 in human islets was assessed by knocking down its expression with lentiviral single hairpin RNA (lenti-shRNA)-RFP. Biphasic GSIS was determined by islet perifusion assay. Single-cell analysis of exocytosis of red fluorescent protein (RFP)-positive beta cells (exhibiting near-total depletion of Syn-4) was by patch clamp capacitance measurements (Cm) and total internal reflection fluorescence microscopy (TIRFM), the latter to further assess single SG behaviour. Co-immunoprecipitations were conducted on INS-1 cells to assess exocytotic complexes. Syn-4 knockdown (KD) of 77% in human islets caused a concomitant reduction in cognate Munc18c expression (46%) without affecting expression of other exocytotic proteins; this resulted in reduction of GSIS in the first phase (by 42%) and the second phase (by 40%). Cm of RFP-tagged Syn-4-KD beta cells showed severe inhibition in the readily releasable pool (by 71%) and mobilisation from reserve pools (by 63%). TIRFM showed that Syn-4-KD-induced inhibition of first-phase GSIS was attributed to reduction in exocytosis of both pre-docked and newcomer SGs (which undergo minimal residence or docking time at the plasma membrane before fusion). Second-phase inhibition was attributed to reduction in newcomer SGs. Stx-4 co-immunoprecipitated Munc18c, VAMP2 and VAMP8, suggesting that these exocytotic complexes may be involved in exocytosis of pre-docked and newcomer SGs. Syn-4 is involved in distinct molecular machineries that influence exocytosis of both pre-docked and newcomer SGs in a manner functionally redundant to Syn-1A and

  14. C-Terminal Tyrosine Residue Modifications Modulate the Protective Phosphorylation of Serine 129 of α-Synuclein in a Yeast Model of Parkinson's Disease

    PubMed Central

    Lázaro, Diana F.; Pinho, Raquel; Valerius, Oliver; Outeiro, Tiago F.; Braus, Gerhard H.

    2016-01-01

    Parkinson´s disease (PD) is characterized by the presence of proteinaceous inclusions called Lewy bodies that are mainly composed of α-synuclein (αSyn). Elevated levels of oxidative or nitrative stresses have been implicated in αSyn related toxicity. Phosphorylation of αSyn on serine 129 (S129) modulates autophagic clearance of inclusions and is prominently found in Lewy bodies. The neighboring tyrosine residues Y125, Y133 and Y136 are phosphorylation and nitration sites. Using a yeast model of PD, we found that Y133 is required for protective S129 phosphorylation and for S129-independent proteasome clearance. αSyn can be nitrated and form stable covalent dimers originating from covalent crosslinking of two tyrosine residues. Nitrated tyrosine residues, but not di-tyrosine-crosslinked dimers, contributed to αSyn cytotoxicity and aggregation. Analysis of tyrosine residues involved in nitration and crosslinking revealed that the C-terminus, rather than the N-terminus of αSyn, is modified by nitration and di-tyrosine formation. The nitration level of wild-type αSyn was higher compared to that of A30P mutant that is non-toxic in yeast. A30P formed more dimers than wild-type αSyn, suggesting that dimer formation represents a cellular detoxification pathway in yeast. Deletion of the yeast flavohemoglobin gene YHB1 resulted in an increase of cellular nitrative stress and cytotoxicity leading to enhanced aggregation of A30P αSyn. Yhb1 protected yeast from A30P-induced mitochondrial fragmentation and peroxynitrite-induced nitrative stress. Strikingly, overexpression of neuroglobin, the human homolog of YHB1, protected against αSyn inclusion formation in mammalian cells. In total, our data suggest that C-terminal Y133 plays a major role in αSyn aggregate clearance by supporting the protective S129 phosphorylation for autophagy and by promoting proteasome clearance. C-terminal tyrosine nitration increases pathogenicity and can only be partially detoxified by αSyn

  15. C-Terminal Tyrosine Residue Modifications Modulate the Protective Phosphorylation of Serine 129 of α-Synuclein in a Yeast Model of Parkinson's Disease.

    PubMed

    Kleinknecht, Alexandra; Popova, Blagovesta; Lázaro, Diana F; Pinho, Raquel; Valerius, Oliver; Outeiro, Tiago F; Braus, Gerhard H

    2016-06-01

    Parkinson´s disease (PD) is characterized by the presence of proteinaceous inclusions called Lewy bodies that are mainly composed of α-synuclein (αSyn). Elevated levels of oxidative or nitrative stresses have been implicated in αSyn related toxicity. Phosphorylation of αSyn on serine 129 (S129) modulates autophagic clearance of inclusions and is prominently found in Lewy bodies. The neighboring tyrosine residues Y125, Y133 and Y136 are phosphorylation and nitration sites. Using a yeast model of PD, we found that Y133 is required for protective S129 phosphorylation and for S129-independent proteasome clearance. αSyn can be nitrated and form stable covalent dimers originating from covalent crosslinking of two tyrosine residues. Nitrated tyrosine residues, but not di-tyrosine-crosslinked dimers, contributed to αSyn cytotoxicity and aggregation. Analysis of tyrosine residues involved in nitration and crosslinking revealed that the C-terminus, rather than the N-terminus of αSyn, is modified by nitration and di-tyrosine formation. The nitration level of wild-type αSyn was higher compared to that of A30P mutant that is non-toxic in yeast. A30P formed more dimers than wild-type αSyn, suggesting that dimer formation represents a cellular detoxification pathway in yeast. Deletion of the yeast flavohemoglobin gene YHB1 resulted in an increase of cellular nitrative stress and cytotoxicity leading to enhanced aggregation of A30P αSyn. Yhb1 protected yeast from A30P-induced mitochondrial fragmentation and peroxynitrite-induced nitrative stress. Strikingly, overexpression of neuroglobin, the human homolog of YHB1, protected against αSyn inclusion formation in mammalian cells. In total, our data suggest that C-terminal Y133 plays a major role in αSyn aggregate clearance by supporting the protective S129 phosphorylation for autophagy and by promoting proteasome clearance. C-terminal tyrosine nitration increases pathogenicity and can only be partially detoxified by αSyn

  16. The contribution of alpha synuclein to neuronal survival and function - Implications for Parkinson's disease.

    PubMed

    Benskey, Matthew J; Perez, Ruth G; Manfredsson, Fredric P

    2016-05-01

    The aggregation of alpha synuclein (α-syn) is a neuropathological feature that defines a spectrum of disorders collectively termed synucleinopathies, and of these, Parkinson's disease (PD) is arguably the best characterized. Aggregated α-syn is the primary component of Lewy bodies, the defining pathological feature of PD, while mutations or multiplications in the α-syn gene result in familial PD. The high correlation between α-syn burden and PD has led to the hypothesis that α-syn aggregation produces toxicity through a gain-of-function mechanism. However, α-syn has been implicated to function in a diverse range of essential cellular processes such as the regulation of neurotransmission and response to cellular stress. As such, an alternative hypothesis with equal explanatory power is that the aggregation of α-syn results in toxicity because of a toxic loss of necessary α-syn function, following sequestration of functional forms α-syn into insoluble protein aggregates. Within this review, we will provide an overview of the literature linking α-syn to PD and the knowledge gained from current α-syn-based animal models of PD. We will then interpret these data from the viewpoint of the α-syn loss-of-function hypothesis and provide a potential mechanistic model by which loss of α-syn function could result in at least some of the neurodegeneration observed in PD. By providing an alternative perspective on the etiopathogenesis of PD and synucleinopathies, this may reveal alternative avenues of research in order to identify potential novel therapeutic targets for disease modifying strategies. The correlation between α-synuclein burden and Parkinson's disease pathology has led to the hypothesis that α-synuclein aggregation produces toxicity through a gain-of-function mechanism. However, in this review, we discuss data supporting the alternative hypothesis that the aggregation of α-synuclein results in toxicity because of loss of necessary

  17. Prevalence and diversity of gastrointestinal helminths in free-ranging Asian house shrew (Suncus murinus) in Bangladesh.

    PubMed

    Rahman, Mizanur; Islam, Shariful; Masuduzzaman, Md; Alam, Mahabub; Chawdhury, Mohammad Nizam Uddin; Ferdous, Jinnat; Islam, Md Nurul; Hassan, Mohammad Mahmudul; Hossain, Mohammad Alamgir; Islam, Ariful

    2018-04-01

    Asian house shrew ( Suncus murinus ), a widely distributed small mammal in the South Asian region, can carry helminths of zoonotic importance. The aim of the study was to know the prevalence and diversity of gastrointestinal (GI) helminths in free-ranging Asian house shrew ( S. murinus ) in Bangladesh. A total of 86 Asian house shrews were captured from forest areas and other habitats of Bangladesh in 2015. Gross examination of the whole GI tract was performed for gross helminth detection, and coproscopy was done for identification of specific eggs or larvae. The overall prevalence of GI helminth was 77.9% (67/86), with six species including nematodes (3), cestodes (2), and trematodes (1). Of the detected helminths, the dominant parasitic group was from the genus Hymenolepis spp.(59%), followed by Strongyloides spp.(17%), Capillaria spp. (10%), Physaloptera spp. (3%), and Echinostoma spp.(3%). The finding shows that the presence of potential zoonotic parasites (Hymenolepis spp. and Capillaria spp.) in Asian house shrew is ubiquitous in all types of habitat (forest land, cropland and dwelling) in Bangladesh. Therefore, further investigation is crucial to examine their role in the transmission of human helminthiasis.

  18. Molecular characterization of Trichuris serrata.

    PubMed

    Ketzis, Jennifer K; Verma, Ashutosh; Burgess, Graham

    2015-05-01

    Trichuris serrata, a whipworm of cats, can cause inflammation in the cecum and upper portion of the large intestine. It is unknown if the virulence and pathology of T. serrata differ from Trichuris campanula, the other species in cats. Distinguishing the species based on egg size is challenging. In addition, Trichuris eggs can be difficult to distinguish from Capillaria spp. This paper presents the first molecular description of T. serrata. The 18S ribosomal RNA (rRNA) gene was sequenced from male adult worms sourced from two unrelated cats on St. Kitts. Based on the analysis of 651 base pairs, T. serrata was found to be different than any other Trichuris species for which published sequencing of the 18S rRNA gene is available. A dendrogram was developed using Molecular Evolutionary Genetics Analysis version 6.0, and evolutionary history was inferred using the minimum evolution method. T. serrata was found to be most closely related to Trichuris vulpis, the Trichuris of dogs. Further development of the methodology could enable distinguishing T. serrata, T. campanula, and Capillaria spp. infections in cats and aid in diagnosis.

  19. On the identity of some weevil species described by Johann Christian Fabricius (1745-1808) in the Museum of Zoology of Copenhagen (Coleoptera, Cucujoidea, Curculionoidea, Tenebrionoidea).

    PubMed

    Alonso-Zarazaga, Miguel A

    2014-01-01

    ) (from Attelabus), Nerthopssticticus (Fabricius, 1777) (from Curculio), Piezotracheluscrotalariae (Fabricius, 1802) (from Attelabus), and Poropterusgranulatus (Fabricius, 1802) (from Curculio). The junior homonym Brachycerusuva Fabricius, 1792 (non Sparrman, 1785) is replaced by Brachycerusfabricii nom. n. The following new synonymies are established: Brachycerusobesus (Fabricius, 1775) = Curculioscalaris Fabricius, 1777, syn. n., Brachydereslusitanicus (Fabricius, 1781) = Curculiomoratus Fabricius, 1798, syn. n., Brachypera (Brachypera) crinita (Boheman, 1834) = Curculiostriatus Fabricius, 1787, syn. n., Brachysomuserinaceus (Fabricius, 1802) = Brachysomusvillosulus (Germar, 1824), syn. n., Bronchusabruptecostatus (Gyllenhal, 1833) = Curculiospectrum Fabricius, 1802, syn. n., Bronchusnivosus (Sparrman, 1785) = Curculiorecurvus Fabricius, 1802, syn. n., Camptorhinustibialis (Sparrman, 1785) = Rhynchaenusalienatus Fabricius, 1802, syn. n., Coelocephalapionatrirostre (Fabricius, 1802) = Coelocephalapionluteirostre (Gerstäcker, 1854), syn. n., Cyrtoderescristatus (DeGeer, 1778) (Tenebrionidae) = Brachyceruscristatus Fabricius, 1798, syn. n., Desmidophorushebes (Fabricius, 1781) = Curculiotuberculatus Fabricius, 1792, syn. n., Donussalviae (Schrank, 1789) = Curculiodenticornis Fabricius, 1798, syn. n., Exomiasholosericeus (Fabricius, 1802) = Exomiaschevrolati (Boheman, 1842), syn. n., Nerthopssticticus (Fabricius, 1777) = Nerthopsguttatus (Olivier, 1807), syn. n., Phyllobiusoblongus (Linnaeus, 1758) = Curculiomali Fabricius, 1782, syn. n., and Rhinocyllusconicus (Froelich, 1792) = Bruchuspunctatus Fabricius, 1798, syn. n. Bronchussynthesys sp. n. is described to represent the concept of Hipporhinusspectrum sensu Marshall, 1904, a misidentification.

  20. Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles.

    PubMed

    Doucet, Marika; El-Turabi, Aadil; Zabel, Franziska; Hunn, Benjamin H M; Bengoa-Vergniory, Nora; Cioroch, Milena; Ramm, Mauricio; Smith, Amy M; Gomes, Ariane Cruz; Cabral de Miranda, Gustavo; Wade-Martins, Richard; Bachmann, Martin F

    2017-01-01

    Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model.

  1. Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles

    PubMed Central

    Zabel, Franziska; Hunn, Benjamin H.M.; Bengoa-Vergniory, Nora; Cioroch, Milena; Ramm, Mauricio; Smith, Amy M.; Gomes, Ariane Cruz; Cabral de Miranda, Gustavo; Wade-Martins, Richard; Bachmann, Martin F.

    2017-01-01

    Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model. PMID:28797124

  2. Serine 129 phosphorylation of membrane-associated α-synuclein modulates dopamine transporter function in a G protein–coupled receptor kinase–dependent manner

    PubMed Central

    Hara, Susumu; Arawaka, Shigeki; Sato, Hiroyasu; Machiya, Youhei; Cui, Can; Sasaki, Asuka; Koyama, Shingo; Kato, Takeo

    2013-01-01

    Most α-synuclein (α-syn) deposited in Lewy bodies, the pathological hallmark of Parkinson disease (PD), is phosphorylated at Ser-129. However, the physiological and pathological roles of this modification are unclear. Here we investigate the effects of Ser-129 phosphorylation on dopamine (DA) uptake in dopaminergic SH-SY5Y cells expressing α-syn. Subcellular fractionation of small interfering RNA (siRNA)–treated cells shows that G protein–coupled receptor kinase 3 (GRK3), GRK5, GRK6, and casein kinase 2 (CK2) contribute to Ser-129 phosphorylation of membrane-associated α-syn, whereas cytosolic α-syn is phosphorylated exclusively by CK2. Expression of wild-type α-syn increases DA uptake, and this effect is diminished by introducing the S129A mutation into α-syn. However, wild-type and S129A α-syn equally increase the cell surface expression of dopamine transporter (DAT) in SH-SY5Y cells and nonneuronal HEK293 cells. In addition, siRNA-mediated knockdown of GRK5 or GRK6 significantly attenuates DA uptake without altering DAT cell surface expression, whereas knockdown of CK2 has no effect on uptake. Taken together, our results demonstrate that membrane-associated α-syn enhances DA uptake capacity of DAT by GRKs-mediated Ser-129 phosphorylation, suggesting that α-syn modulates intracellular DA levels with no functional redundancy in Ser-129 phosphorylation between GRKs and CK2. PMID:23576548

  3. The Potential Role of Toll-Like Receptor 4 in Mediating Dopaminergic Cell Loss and Alpha-Synuclein Expression in the Acute MPTP Mouse Model of Parkinson's Disease.

    PubMed

    Mariucci, Giuseppina; Pagiotti, Rita; Galli, Francesco; Romani, Luigina; Conte, Carmela

    2018-04-01

    Toll-like receptors (TLRs) may have a role in Parkinson's disease (PD). In this study, we aimed at investigating the dopaminergic cell loss and alpha-synuclein (α-SYN) expression in TLR4-deficient mice (TLR4 -/- ) acutely exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a pharmacological PD model. TLR4 ablation restrained the number of dopaminergic neurons in the substantia nigra (SN), as assessed by tyrosine hydroxylase (TH) protein expression. Intriguingly, TLR4 -/- mice showed massive α-SYN protein accumulation in the midbrain along with high α-SYN mRNA levels in cerebral cortex, striatum, hippocampus, and cerebellum. Contrary to expectations, the high levels of α-SYN do not correlate with greater dopaminergic neuronal loss. The levels of nigral α-SYN protein in TLR4 -/- mice further, but not significantly, increased during MPTP treatment. Contrariwise, MPTP treatment significantly induced the mRNA expression of α-SYN in examined brain regions of WT and TLR4 -/- mice. Protein levels of GATA2, a transcription factor proposed to control α-SYN gene expression, did not change in TLR4 -/- mice at baseline and after MPTP treatment. These findings suggest a role for TLR4 in mediating dopaminergic cell loss and in the constitutive expression of brain α-SYN. However, further exploration is needed in order to establish the actual role of α-SYN in the relative absence of TLR4.

  4. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

    PubMed

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-02-23

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

  5. Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity

    PubMed Central

    Villar-Piqué, Anna; Lopes da Fonseca, Tomás; Sant’Anna, Ricardo; Szegö, Éva Mónika; Fonseca-Ornelas, Luis; Pinho, Raquel; Carija, Anita; Gerhardt, Ellen; Masaracchia, Caterina; Abad Gonzalez, Enrique; Rossetti, Giulia; Carloni, Paolo; Fernández, Claudio O.; Foguel, Debora; Milosevic, Ira; Zweckstetter, Markus; Ventura, Salvador; Outeiro, Tiago Fleming

    2016-01-01

    Synucleinopathies are a group of progressive disorders characterized by the abnormal aggregation and accumulation of α-synuclein (aSyn), an abundant neuronal protein that can adopt different conformations and biological properties. Recently, aSyn pathology was shown to spread between neurons in a prion-like manner. Proteins like aSyn that exhibit self-propagating capacity appear to be able to adopt different stable conformational states, known as protein strains, which can be modulated both by environmental and by protein-intrinsic factors. Here, we analyzed these factors and found that the unique combination of the neurodegeneration-related metal copper and the pathological H50Q aSyn mutation induces a significant alteration in the aggregation properties of aSyn. We compared the aggregation of WT and H50Q aSyn with and without copper, and assessed the effects of the resultant protein species when applied to primary neuronal cultures. The presence of copper induces the formation of structurally different and less-damaging aSyn aggregates. Interestingly, these aggregates exhibit a stronger capacity to induce aSyn inclusion formation in recipient cells, which demonstrates that the structural features of aSyn species determine their effect in neuronal cells and supports a lack of correlation between toxicity and inclusion formation. In total, our study provides strong support in favor of the hypothesis that protein aggregation is not a primary cause of cytotoxicity. PMID:27708160

  6. The proinflammatory cytokines IL-1beta and TNF-alpha induce the expression of Synoviolin, an E3 ubiquitin ligase, in mouse synovial fibroblasts via the Erk1/2-ETS1 pathway.

    PubMed

    Gao, Beixue; Calhoun, Karen; Fang, Deyu

    2006-01-01

    The overgrowth of synovial tissues is critical in the pathogenesis of rheumatoid arthritis (RA). The expression of Synoviolin (SYN), an E3 ubiquitin ligase, is upregulated in arthritic synovial fibroblasts and is involved in the overgrowth of synovial cells during RA. However, the molecular mechanisms involved in the elevated SYN expression are not known. Here, we found that SYN expression is elevated in the synovial fibroblasts from mice with collagen-induced arthritis (CIA). The proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha) induce SYN expression in mouse synovial fibroblasts. Cultivation of mouse synovial fibroblasts with IL-1beta activates mitogen-activated protein kinases, including extra-cellular signal-regulated kinase (Erk), JNK (c-Jun N-terminal kinase), and p38, while only Erk-specific inhibitor blocks IL-1beta-induced SYN expression. Expression of transcription factor ETS1 further enhances IL-1beta-induced SYN expression. The dominant negative ETS1 mutant lacking the transcription activation domain inhibits SYN expression in a dose-dependent manner. The activation of both Erk1/2 and ETS1 is increased in the CIA synovial fibroblasts. Inhibition of Erk activation reduces ETS1 phosphorylation and SYN expression. Our data indicate that the proinflammatory cytokines IL-1beta and TNF-alpha induce the overgrowth of synovial cells by upregulating SYN expression via the Erk1/-ETS1 pathway. These molecules or pathways could therefore be potential targets for the treatment of RA.

  7. The proinflammatory cytokines IL-1β and TNF-α induce the expression of Synoviolin, an E3 ubiquitin ligase, in mouse synovial fibroblasts via the Erk1/2-ETS1 pathway

    PubMed Central

    Gao, Beixue; Calhoun, Karen; Fang, Deyu

    2006-01-01

    The overgrowth of synovial tissues is critical in the pathogenesis of rheumatoid arthritis (RA). The expression of Synoviolin (SYN), an E3 ubiquitin ligase, is upregulated in arthritic synovial fibroblasts and is involved in the overgrowth of synovial cells during RA. However, the molecular mechanisms involved in the elevated SYN expression are not known. Here, we found that SYN expression is elevated in the synovial fibroblasts from mice with collagen-induced arthritis (CIA). The proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) induce SYN expression in mouse synovial fibroblasts. Cultivation of mouse synovial fibroblasts with IL-1β activates mitogen-activated protein kinases, including extra-cellular signal-regulated kinase (Erk), JNK (c-Jun N-terminal kinase), and p38, while only Erk-specific inhibitor blocks IL-1β-induced SYN expression. Expression of transcription factor ETS1 further enhances IL-1β-induced SYN expression. The dominant negative ETS1 mutant lacking the transcription activation domain inhibits SYN expression in a dose-dependent manner. The activation of both Erk1/2 and ETS1 is increased in the CIA synovial fibroblasts. Inhibition of Erk activation reduces ETS1 phosphorylation and SYN expression. Our data indicate that the proinflammatory cytokines IL-1β and TNF-α induce the overgrowth of synovial cells by upregulating SYN expression via the Erk1/-ETS1 pathway. These molecules or pathways could therefore be potential targets for the treatment of RA. PMID:17105652

  8. Data in support of the identification of neuronal and astrocyte proteins interacting with extracellularly applied oligomeric and fibrillar α-synuclein assemblies by mass spectrometry

    PubMed Central

    Shrivastava, Amulya Nidhi; Redeker, Virginie; Fritz, Nicolas; Pieri, Laura; Almeida, Leandro G.; Spolidoro, Maria; Liebmann, Thomas; Bousset, Luc; Renner, Marianne; Léna, Clément; Aperia, Anita; Melki, Ronald; Triller, Antoine

    2016-01-01

    α-Synuclein (α-syn) is the principal component of Lewy bodies, the pathophysiological hallmark of individuals affected by Parkinson disease (PD). This neuropathologic form of α-syn contributes to PD progression and propagation of α-syn assemblies between neurons. The data we present here support the proteomic analysis used to identify neuronal proteins that specifically interact with extracellularly applied oligomeric or fibrillar α-syn assemblies (conditions 1 and 2, respectively) (doi: 10.15252/embj.201591397[1]). α-syn assemblies and their cellular partner proteins were pulled down from neuronal cell lysed shortly after exposure to exogenous α-syn assemblies and the associated proteins were identified by mass spectrometry using a shotgun proteomic-based approach. We also performed experiments on pure cultures of astrocytes to identify astrocyte-specific proteins interacting with oligomeric or fibrillar α-syn (conditions 3 and 4, respectively). For each condition, proteins interacting selectively with α-syn assemblies were identified by comparison to proteins pulled-down from untreated cells used as controls. The mass spectrometry data, the database search and the peak lists have been deposited to the ProteomeXchange Consortium database via the PRIDE partner repository with the dataset identifiers PRIDE: PXD002256 to PRIDE: PXD002263 and doi: 10.6019/PXD002256 to 10.6019/PXD002263. PMID:26958642

  9. Data in support of the identification of neuronal and astrocyte proteins interacting with extracellularly applied oligomeric and fibrillar α-synuclein assemblies by mass spectrometry.

    PubMed

    Shrivastava, Amulya Nidhi; Redeker, Virginie; Fritz, Nicolas; Pieri, Laura; Almeida, Leandro G; Spolidoro, Maria; Liebmann, Thomas; Bousset, Luc; Renner, Marianne; Léna, Clément; Aperia, Anita; Melki, Ronald; Triller, Antoine

    2016-06-01

    α-Synuclein (α-syn) is the principal component of Lewy bodies, the pathophysiological hallmark of individuals affected by Parkinson disease (PD). This neuropathologic form of α-syn contributes to PD progression and propagation of α-syn assemblies between neurons. The data we present here support the proteomic analysis used to identify neuronal proteins that specifically interact with extracellularly applied oligomeric or fibrillar α-syn assemblies (conditions 1 and 2, respectively) (doi: 10.15252/embj.201591397[1]). α-syn assemblies and their cellular partner proteins were pulled down from neuronal cell lysed shortly after exposure to exogenous α-syn assemblies and the associated proteins were identified by mass spectrometry using a shotgun proteomic-based approach. We also performed experiments on pure cultures of astrocytes to identify astrocyte-specific proteins interacting with oligomeric or fibrillar α-syn (conditions 3 and 4, respectively). For each condition, proteins interacting selectively with α-syn assemblies were identified by comparison to proteins pulled-down from untreated cells used as controls. The mass spectrometry data, the database search and the peak lists have been deposited to the ProteomeXchange Consortium database via the PRIDE partner repository with the dataset identifiers PRIDE: PXD002256 to PRIDE: PXD002263 and doi: 10.6019/PXD002256 to 10.6019/PXD002263.

  10. Munc18-1 is a molecular chaperone for α-synuclein, controlling its self-replicating aggregation.

    PubMed

    Chai, Ye Jin; Sierecki, Emma; Tomatis, Vanesa M; Gormal, Rachel S; Giles, Nichole; Morrow, Isabel C; Xia, Di; Götz, Jürgen; Parton, Robert G; Collins, Brett M; Gambin, Yann; Meunier, Frédéric A

    2016-09-12

    Munc18-1 is a key component of the exocytic machinery that controls neurotransmitter release. Munc18-1 heterozygous mutations cause developmental defects and epileptic phenotypes, including infantile epileptic encephalopathy (EIEE), suggestive of a gain of pathological function. Here, we used single-molecule analysis, gene-edited cells, and neurons to demonstrate that Munc18-1 EIEE-causing mutants form large polymers that coaggregate wild-type Munc18-1 in vitro and in cells. Surprisingly, Munc18-1 EIEE mutants also form Lewy body-like structures that contain α-synuclein (α-Syn). We reveal that Munc18-1 binds α-Syn, and its EIEE mutants coaggregate α-Syn. Likewise, removal of endogenous Munc18-1 increases the aggregative propensity of α-Syn(WT) and that of the Parkinson's disease-causing α-Syn(A30P) mutant, an effect rescued by Munc18-1(WT) expression, indicative of chaperone activity. Coexpression of the α-Syn(A30P) mutant with Munc18-1 reduced the number of α-Syn(A30P) aggregates. Munc18-1 mutations and haploinsufficiency may therefore trigger a pathogenic gain of function through both the corruption of native Munc18-1 and a perturbed chaperone activity for α-Syn leading to aggregation-induced neurodegeneration. © 2016 Chai et al.

  11. Lysosomal enzyme cathepsin B enhances the aggregate forming activity of exogenous α-synuclein fibrils.

    PubMed

    Tsujimura, Atsushi; Taguchi, Katsutoshi; Watanabe, Yoshihisa; Tatebe, Harutsugu; Tokuda, Takahiko; Mizuno, Toshiki; Tanaka, Masaki

    2015-01-01

    The formation of intracellular aggregates containing α-synuclein (α-Syn) is one of the key steps in the progression of Parkinson's disease and dementia with Lewy bodies. Recently, it was reported that pathological α-Syn fibrils can undergo cell-to-cell transmission and form Lewy body-like aggregates. However, little is known about how they form α-Syn aggregates from fibril seeds. Here, we developed an assay to study the process of aggregate formation using fluorescent protein-tagged α-Syn-expressing cells and examined the aggregate forming activity of exogenous α-Syn fibrils. α-Syn fibril-induced formation of intracellular aggregates was suppressed by a cathepsin B specific inhibitor, but not by a cathepsin D inhibitor. α-Syn fibrils pretreated with cathepsin B in vitro enhanced seeding activity in cells. Knockdown of cathepsin B also reduced fibril-induced aggregate formation. Moreover, using LAMP-1 immunocytochemistry and live-cell imaging, we observed that these aggregates initially occurred in the lysosome. They then rapidly grew larger and moved outside the boundary of the lysosome within one day. These results suggest that the lysosomal protease cathepsin B is involved in triggering intracellular aggregate formation by α-Syn fibrils. Copyright © 2015. Published by Elsevier Inc.

  12. Munc18-1 is a molecular chaperone for α-synuclein, controlling its self-replicating aggregation

    PubMed Central

    Giles, Nichole; Morrow, Isabel C.; Collins, Brett M.

    2016-01-01

    Munc18-1 is a key component of the exocytic machinery that controls neurotransmitter release. Munc18-1 heterozygous mutations cause developmental defects and epileptic phenotypes, including infantile epileptic encephalopathy (EIEE), suggestive of a gain of pathological function. Here, we used single-molecule analysis, gene-edited cells, and neurons to demonstrate that Munc18-1 EIEE-causing mutants form large polymers that coaggregate wild-type Munc18-1 in vitro and in cells. Surprisingly, Munc18-1 EIEE mutants also form Lewy body–like structures that contain α-synuclein (α-Syn). We reveal that Munc18-1 binds α-Syn, and its EIEE mutants coaggregate α-Syn. Likewise, removal of endogenous Munc18-1 increases the aggregative propensity of α-SynWT and that of the Parkinson’s disease–causing α-SynA30P mutant, an effect rescued by Munc18-1WT expression, indicative of chaperone activity. Coexpression of the α-SynA30P mutant with Munc18-1 reduced the number of α-SynA30P aggregates. Munc18-1 mutations and haploinsufficiency may therefore trigger a pathogenic gain of function through both the corruption of native Munc18-1 and a perturbed chaperone activity for α-Syn leading to aggregation-induced neurodegeneration. PMID:27597756

  13. Metabolic Syndrome Does Not Detect Metabolic Risk in African Men Living in the U.S.

    PubMed Central

    Ukegbu, Ugochi J.; Castillo, Darleen C.; Knight, Michael G.; Ricks, Madia; Miller, Bernard V.; Onumah, Barbara M.; Sumner, Anne E.

    2011-01-01

    OBJECTIVE Metabolic risk and metabolic syndrome (MetSyn) prevalence were compared in Africans who immigrated to the U.S. and African Americans. If MetSyn were an effective predictor of cardiometabolic risk, then the group with a worse metabolic risk profile would have a higher rate of MetSyn. RESEARCH DESIGN AND METHODS Cross-sectional analyses were performed on 95 men (39 Africans, 56 African Americans, age 38 ± 6 years [mean ± SD]). Glucose tolerance was determined by oral glucose tolerance test, visceral adipose tissue (VAT) was determined by computerized tomography, and MetSyn was determined by the presence of three of five factors: central obesity, hypertriglyceridemia, low levels of HDL cholesterol, hypertension, and fasting hyperglycemia. RESULTS MetSyn prevalence was similar in Africans and African Americans (10 vs. 13%, P = 0.74), but hypertension, glycemia (fasting and 2-h glucose), and VAT were higher in Africans. CONCLUSIONS African immigrants have a worse metabolic profile than African Americans but a similar prevalence of MetSyn. Therefore, MetSyn may underpredict metabolic risk in Africans. PMID:21873563

  14. Metabolic syndrome does not detect metabolic risk in African men living in the U.S.

    PubMed

    Ukegbu, Ugochi J; Castillo, Darleen C; Knight, Michael G; Ricks, Madia; Miller, Bernard V; Onumah, Barbara M; Sumner, Anne E

    2011-10-01

    Metabolic risk and metabolic syndrome (MetSyn) prevalence were compared in Africans who immigrated to the U.S. and African Americans. If MetSyn were an effective predictor of cardiometabolic risk, then the group with a worse metabolic risk profile would have a higher rate of MetSyn. Cross-sectional analyses were performed on 95 men (39 Africans, 56 African Americans, age 38 ± 6 years [mean ± SD]). Glucose tolerance was determined by oral glucose tolerance test, visceral adipose tissue (VAT) was determined by computerized tomography, and MetSyn was determined by the presence of three of five factors: central obesity, hypertriglyceridemia, low levels of HDL cholesterol, hypertension, and fasting hyperglycemia. MetSyn prevalence was similar in Africans and African Americans (10 vs. 13%, P = 0.74), but hypertension, glycemia (fasting and 2-h glucose), and VAT were higher in Africans. African immigrants have a worse metabolic profile than African Americans but a similar prevalence of MetSyn. Therefore, MetSyn may underpredict metabolic risk in Africans.

  15. Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein.

    PubMed

    Tyson, Trevor; Senchuk, Megan; Cooper, Jason F; George, Sonia; Van Raamsdonk, Jeremy M; Brundin, Patrik

    2017-08-08

    Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson's disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, α-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a C. elegans model that mirrors this progression and allows us to monitor α-syn neuron-to-neuron transmission in a live animal over its lifespan. We found that modulation of autophagy or exo/endocytosis, affects α-syn transfer. Furthermore, we demonstrate that silencing C. elegans orthologs of PD-related genes also increases the accumulation of α-syn. This novel worm model is ideal for screening molecules and genes to identify those that modulate prion-like spreading of α-syn in order to target novel strategies for disease modification in PD and other synucleinopathies.

  16. Role of α-synuclein in inducing innate and adaptive immunity in Parkinson disease

    PubMed Central

    Allen Reish, Heather E.; Standaert, David G.

    2015-01-01

    Alpha-synuclein (α-syn) is central to the pathogenesis of Parkinson disease (PD). Gene duplications, triplications and point mutations in SNCA1, the gene encoding α-syn, cause autosomal dominant forms of PD. Aggregated and post-translationally modified forms of α-syn are present in Lewy bodies and Lewy neurites in both sporadic and familial PD, and recent work has emphasized the prion-like ability of aggregated α-syn to produce spreading pathology. Accumulation of abnormal forms of α-syn is a trigger for PD, but recent evidence suggests that much of the downstream neurodegeneration may result from inflammatory responses. Components of both the innate and adaptive immune systems are activated in PD, and influencing interactions between innate and adaptive immune components has been shown to modify the pathological process in animal models of PD. Understanding the relationship between α-syn and subsequent inflammation may reveal novel targets for neuroprotective interventions. In this review, we examine the role of α-syn and modified forms of this protein in the initiation of innate and adaptive immune responses. PMID:25588354

  17. Effects of age, sex, lactation and social dominance on faecal egg count patterns of gastrointestinal nematodes in farmed eland (Taurotragus oryx).

    PubMed

    Vadlejch, J; Kotrba, R; Čadková, Z; Růžičková, A; Langrová, I

    2015-10-01

    The eland is a large African antelope that can be bred in a temperate climate, under similar conditions and production systems as cattle. However, knowledge of parasites in farmed elands outside the area of their native habitat is still limited, and information concerning factors that influence these parasites is lacking. Therefore, faecal samples from an entire herd of elands, including calves and adult females and males, were examined monthly over a one year period. Almost 84% of the animals were found to be positive for gastrointestinal nematodes. Strongyle-type eggs were most frequently detected (prevalence 75%), followed by Capillaria sp., Nematodirus sp. and Trichuris sp. eggs. Following culturing eggs to infective larvae, Teladorsagia sp., Trichostrongylus sp., Nematodirus sp., Cooperia sp. and Oesophagostomum sp. were identified. Following necropsy of two calves that died during the study one abomasal nematode (Teladorsagia circumcincta), five small intestinal nematode species (Nematodirus helvetianus, N. spathiger, Cooperia oncophora, C. curticei and Capillaria bovis) and two large intestinal nematodes (Oesophagostomum venulosum and Trichuris ovis) were recovered. From these findings, it is evident that the eland harbours nematodes that are typical for domestic cattle and small ruminants. Morphological and morphometric analyses of recovered nematodes revealed that these parasites do not require any special morphological adaptation to establish infection in elands. The faecal output of strongyle-type and Nematodirus sp. eggs was seasonal, with the highest egg production taking place during spring and summer. Calves had higher faecal egg counts (for all the monitored nematode species) than adults did. Lactation in females was significantly (P<0.0001) associated with higher strongyle nematode egg shedding. Social dominance also affected faecal egg count patterns. The lower the hierarchical position among adults (regardless of sex), the higher the risk of

  18. SU-G-JeP2-06: Dosimetric and Workflow Evaluation of First Commercial Synthetic CT Software for Clinical Use in Pelvis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tyagi, N; Zhang, J; Happersett, L

    2016-06-15

    Purpose: evaluate a commercial synthetic CT (syn-CT) software for use in prostate radiotherapy Methods: Twenty prostate patients underwent CT and MR simulation scans in treatment position on a 3T Philips scanner. The MR protocol consisted of a T2w turbo spin-echo for soft tissue contrast, a 2D balanced-fast field echo (b-FFE) for fiducial identification, a dual-echo 3D FFE B0 map for distortion analysis and a 3D mDIXON FFE sequence to generate syn-CT. Two echoes are acquired during mDIXON scan, allowing water, fat, and in-phase images to be derived using the frequency shift of the fat and water protons. Tissues were classifiedmore » as: air, adipose, water, trabecular/spongy bone and compact/cortical bone and assigned specific bulk HU values. Bone structures are segmented based on a pelvis bone atlas. Accuracy of syn-CT for patient treatment planning was analyzed by transferring the original plan and structures from the CT to syn-CT via rigid registration and recalculating dose. In addition, new IMRT plans were generated on the syn-CT using structures contoured on MR and transferred to the syn-CT. Accuracy of fiducial-based localization at the treatment machine performed using syn-CT or DRRs generated from syn-CT was assessed by comparing to orthogonal kV radiographs or CBCT. Results: Dosimetric comparison between CT and syn-CT was within 0.5% for all structures. The de-novo optimized plans generated on the syn-CT met our institutional clinical objectives for target and normal structures. Patient-induced susceptibility distortion based on B0 maps was within 1mm and 0.4 mm in the body and prostate. The rectal and bladder outlines on the syn-CT were deemed sufficient for assessing rectal and bladder filling on the CBCT at the time of treatment. CBCT localization showed a median error of < ±1 mm in LR, AP and SI direction. Conclusion: MRI derived syn-CT can be used clinically in MR-alone planning and treatment process for prostate. Drs. Deasy, Hunt and Tyagi have

  19. α-Synuclein in Central Nervous System and from Erythrocytes, Mammalian Cells, and Escherichia coli Exists Predominantly as Disordered Monomer*

    PubMed Central

    Fauvet, Bruno; Mbefo, Martial K.; Fares, Mohamed-Bilal; Desobry, Carole; Michael, Sarah; Ardah, Mustafa T.; Tsika, Elpida; Coune, Philippe; Prudent, Michel; Lion, Niels; Eliezer, David; Moore, Darren J.; Schneider, Bernard; Aebischer, Patrick; El-Agnaf, Omar M.; Masliah, Eliezer; Lashuel, Hilal A.

    2012-01-01

    Since the discovery and isolation of α-synuclein (α-syn) from human brains, it has been widely accepted that it exists as an intrinsically disordered monomeric protein. Two recent studies suggested that α-syn produced in Escherichia coli or isolated from mammalian cells and red blood cells exists predominantly as a tetramer that is rich in α-helical structure (Bartels, T., Choi, J. G., and Selkoe, D. J. (2011) Nature 477, 107–110; Wang, W., Perovic, I., Chittuluru, J., Kaganovich, A., Nguyen, L. T. T., Liao, J., Auclair, J. R., Johnson, D., Landeru, A., Simorellis, A. K., Ju, S., Cookson, M. R., Asturias, F. J., Agar, J. N., Webb, B. N., Kang, C., Ringe, D., Petsko, G. A., Pochapsky, T. C., and Hoang, Q. Q. (2011) Proc. Natl. Acad. Sci. 108, 17797–17802). However, it remains unknown whether or not this putative tetramer is the main physiological form of α-syn in the brain. In this study, we investigated the oligomeric state of α-syn in mouse, rat, and human brains. To assess the conformational and oligomeric state of native α-syn in complex mixtures, we generated α-syn standards of known quaternary structure and conformational properties and compared the behavior of endogenously expressed α-syn to these standards using native and denaturing gel electrophoresis techniques, size-exclusion chromatography, and an oligomer-specific ELISA. Our findings demonstrate that both human and rodent α-syn expressed in the central nervous system exist predominantly as an unfolded monomer. Similar results were observed when human α-syn was expressed in mouse and rat brains as well as mammalian cell lines (HEK293, HeLa, and SH-SY5Y). Furthermore, we show that α-syn expressed in E. coli and purified under denaturing or nondenaturing conditions, whether as a free protein or as a fusion construct with GST, is monomeric and adopts a disordered conformation after GST removal. These results do not rule out the possibility that α-syn becomes structured upon interaction

  20. Annotated type catalogue of the Chrysididae (Insecta, Hymenoptera) deposited in the collection of Radoszkowski in the Polish Academy of Sciences, Kraków

    PubMed Central

    Rosa, Paolo; Wiśniowski, Bogdan; Xu, Zai-fu

    2015-01-01

    Abstract A critical and annotated catalogue of 183 types of Hymenoptera Chrysididae belonging to 124 taxa housed in the Radoszkowski collection is given. Radoszkowski type material from other institutes has also been checked. Six lectotypes are designated in Kraków (ISEA-PAN): Chrysis acceptabilis Radoszkowski, 1891; Chrysis persica Radoczkowsky, 1881; Chrysis daphnis Mocsáry, 1889; Chrysis lagodechii Radoszkowski, 1889; Chrysis remota Mocsáry, 1889 and Chrysis vagans Radoszkowski, 1877. The lectotype of Brugmoia pellucida Radoszkowski, 1877 is designated in Moscow (MMU). Four new combinations are proposed: Philoctetes araraticus (Radoszkowski, 1890), comb. n.; Pseudomalus hypocrita (du Buysson, 1893), comb. n.; Chrysis eldari (Radoszkowski, 1893), comb. n.; and Chrysura mlokosewitzi (Radoszkowski, 1889), comb. n.. Ten new synonyms are given: Chrysis auropunctata Mocsáry, 1889, syn. n. of Chrysis angolensis Radoszkovsky, 1881; Chrysis chrysochlora Mocsáry, 1889, syn. n. and Chrysis viridans Radoszkowski, 1891, syn. n. of Chrysis keriensis Radoszkowski, 1887; Chrysis angustifrons var. ignicollis Trautmann, 1926, syn. n. of Chrysis eldari (Radoszkowski, 1893); Chrysis maracandensis var. simulatrix Radoszkowski, 1891, syn. n. of Chrysis maracandensis Radoszkowski, 1877; Chrysis pulchra Radoszkovsky, 1880, syn. n. of Spinolia dallatorreana (Mocsáry, 1896); Chrysis rubricollis du Buysson, 1900, syn. n. of Chrysis eldari (Radoszkowski, 1893); Chrysis subcoerulea Radoszkowski, 1891, syn. n. of Chrysis chlorochrysa Mocsáry, 1889; Chrysis therates Mocsáry, 1889, syn. n. of Chrysis principalis Smith, 1874; and Notozus komarowi Radoszkowski, 1893, syn. n. of Elampus obesus (Mocsáry, 1890). One species is revaluated: Chrysis chalcochrysa Mocsáry, 1887. Chrysis kizilkumiana Rosa is the new name for Chrysis uljanini Radoszkowski & Mocsáry, 1889 nec Radoszkowski, 1877. Pictures of seventy-seven type specimens are given. PMID:25829848

  1. Human serum antibodies against EBV latent membrane protein 1 cross-react with α-synuclein

    PubMed Central

    Gray, Madison T.; Ganesh, Munisha S.; Middeldorp, Jaap M.

    2016-01-01

    Objectives: To identify the epitope on α-synuclein (α-syn) to which antibodies against the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) bind and to determine whether antibodies targeting this mimicry domain are present in human sera. Methods: Reactivity of the α-syn-cross-reacting anti-LMP1 monoclonal antibody CS1-4 to a synthetic peptide containing the putative mimicry domain was compared to those in which this domain was mutated and to murine and rat α-syn (which differ from human α-syn at this site) in Western blots. Using ELISA, sera from EBV+ (n = 4) and EBV− (n = 12) donors as well as those with infectious mononucleosis (IM; n = 120), and Hodgkin disease (HD; n = 33) were interrogated for antibody reactivity to synthetic peptides corresponding to regions of α-syn and LMP1 containing the mimicry domain. Results: CS1-4 showed strong reactivity to wild-type human α-syn, but not to the mutant peptides or rodent α-syn. Control EBV− and EBV+ sera showed no reactivity to α-syn or LMP1 peptides. However, a significant proportion of IM and HD sera contained immunoglobulin M (IgM) (59% and 70%, in IM and HD, respectively), immunoglobulin G (IgG) (40% and 48%), and immunoglobulin A (IgA) (28% and 36%) antibodies to both peptides, as well as a significant correlation in the titers of IgM (ρ = 0.606 and 0.664, for IM and HD, respectively), IgG (0.526 and 0.836), and IgA (0.569 and 0.728) antibodies targeting LMP1 and α-syn peptides. Conclusions: Anti-EBV-LMP1 antibodies cross-reacting with a defined epitope in α-syn are present in human patients. These findings may have implications for the pathogenesis of synucleinopathies. PMID:27218119

  2. The novel Parkinson's disease linked mutation G51D attenuates in vitro aggregation and membrane binding of α-synuclein, and enhances its secretion and nuclear localization in cells

    PubMed Central

    Fares, Mohamed-Bilal; Ait-Bouziad, Nadine; Dikiy, Igor; Mbefo, Martial K.; Jovičić, Ana; Kiely, Aoife; Holton, Janice L.; Lee, Seung-Jae; Gitler, Aaron D.; Eliezer, David; Lashuel, Hilal A.

    2014-01-01

    A novel mutation in the α-Synuclein (α-Syn) gene “G51D” was recently identified in two familial cases exhibiting features of Parkinson's disease (PD) and multiple system atrophy (MSA). In this study, we explored the impact of this novel mutation on the aggregation, cellular and biophysical properties of α-Syn, in an attempt to unravel how this mutant contributes to PD/MSA. Our results show that the G51D mutation significantly attenuates α-Syn aggregation in vitro. Moreover, it disrupts local helix formation in the presence of SDS, decreases binding to lipid vesicles C-terminal to the site of mutation and severely inhibits helical folding in the presence of acidic vesicles. When expressed in yeast, α-SynG51D behaves similarly to α-SynA30P, as both exhibit impaired membrane association, form few inclusions and are non-toxic. In contrast, enhanced secreted and nuclear levels of the G51D mutant were observed in mammalian cells, as well as in primary neurons, where α-SynG51D was enriched in the nuclear compartment, was hyper-phosphorylated at S129 and exacerbated α-Syn-induced mitochondrial fragmentation. Finally, post-mortem human brain tissues of α-SynG51D cases were examined, and revealed only partial colocalization with nuclear membrane markers, probably due to post-mortem tissue delay and fixation. These findings suggest that the PD-linked mutations may cause neurodegeneration via different mechanisms, some of which may be independent of α-Syn aggregation. PMID:24728187

  3. Analog modeling and kinematic restoration of inverted hangingwall synclinal basins developed above syn-kinematic salt: Application to the Lusitanian and Parentis basins

    NASA Astrophysics Data System (ADS)

    Roma, Maria; Vidal-Royo, Oskar; McClay, Ken; Ferrer, Oriol; Muñoz, Josep Anton

    2017-04-01

    The formation of hagingwall syncline basins is basically constrained by the geometry of the basement-involved fault, but also by salt distribution . The formation of such basins is common around the Iberian Peninsula (e.g. Lusitanian, Parentis, Basque-Cantabian, Cameros and Organyà basins) where Upper Triassic (Keuper) salt governed their polyphasic Mesozoic extension and their subsequent Alpine inversion. In this scenario, a precise interpretation of the sub-salt faults geometry and a reconstruction of the initial salt thickness are key to understand the kinematic evolution of such basins. Using an experimental approach (sandbox models) and these Mesozoic basins as natural analogues, the aim of this work is to: 1) investigate the main parameters that controlled the formation and evolution of hagingwall syncline basins analyzing the role of syn-kinematic salt during extension and subsequent inversion; and 2) quantify the deformation and salt mobilization based on restoration of analog model cross sections. The experimental results demonstrate that premature welds are developed by salt deflation with consequent upward propagation of the basal fault in salt-bearing rift systems with a large amount of extension,. In contrast, thicker salt inhibits the upward fault propagation, which results into a further salt migration and development of a hagingwall syncline basins flanked by salt walls. The inherited extensional architecture as well as salt continuity dramatically controlled subsequent inversion. Shortening initially produced the folding and the uplift of the synclinal basins. Minor reverse faults form as a consequence of overtightening of welded diapir stems. However, no trace of reverse faulting is found around diapirs stems, as ductile unit is still available for extrusion, squeezing and accommodation of shortening. Restoration of the sandbox models has demonstrated that this is a powerful tool to unravel the complex structures in the models and this may

  4. Updates to the Nomenclature of Platygastroidea in the Zoological Institute of the Russian Academy of Sciences

    USDA-ARS?s Scientific Manuscript database

    Parabaryconus Kozlov & Kononova n. syn. is treated as a junior synonym of Cremastobaeus Ashmead; Cremastobaeus artus (Kozlov & Kononova) n. comb. is transferred from Parabaryconus; Paridris macrurous Kozlov & Le n. syn. and P. taekuli Talamas & Masner n. syn. are treated as junior synonyms of P. bis...

  5. RNA interference targeting α-synuclein attenuates methamphetamine-induced neurotoxicity in SH-SY5Y cells.

    PubMed

    Chen, Ling; Huang, Enping; Wang, Huijun; Qiu, Pingming; Liu, Chao

    2013-07-12

    The protein α-synuclein (α-syn) is abundant in neurons and has been claimed to play critical roles in the pathophysiology of Parkinson's disease. Overexpression of α-syn has been shown to be toxicity in methamphetamine (METH)-induced model in vivo and in vitro which has Parkinson's-like pathology. However, the exact mechanisms underlying toxicity of α-syn mediated METH-induced neuron remain unknown. In the present study, human dopaminergic-like neuroblastoma SH-SY5Y cells were used as METH-induced model in vitro. Cell viability was found to be dramatically increased after silencing α-syn expression followed by METH treatment compared with a-syn wild-type cells and the morphological damage to cells after METH treatment was abated through knockdown of α-syn expression in this model. The expression levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2(VMAT-2) were significantly decreased and the activity/levels of reactive oxygen species (ROS), nitric oxide synthase (NOS) and nitrogen (NO) were notably increased after METH treatment. However, the changes of these expression levels were reversed in cells transfected with α-syn-shRNA. These results suggested that TH, DAT, VMAT-2, ROS and NOS maybe involved in α-syn mediated METH-induced neuronal toxicity. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression.

    PubMed

    Yang, Li; Stewart, Tessandra; Shi, Min; Pottiez, Gwenael; Dator, Romel; Wu, Rui; Aro, Patrick; Schuster, Robert J; Ginghina, Carmen; Pan, Catherine; Gao, Yuqian; Qian, Weijun; Zabetian, Cyrus P; Hu, Shu-Ching; Quinn, Joseph F; Zhang, Jing

    2017-07-01

    The alpha-synuclein (α-syn) level in human cerebrospinal fluid (CSF), as measured by immunoassays, is promising as a Parkinson's disease (PD) biomarker. However, the levels of total α-syn are inconsistent among studies with large cohorts and different measurement platforms. Total α-syn level also does not correlate with disease severity or progression. Here, the authors developed a highly sensitive MRM method to measure absolute CSF α-syn peptide concentrations without prior enrichment or fractionation, aiming to discover new candidate biomarkers. Six peptides covering 73% of protein sequence were reliably identified, and two were consistently quantified in cross-sectional and longitudinal cohorts. Absolute concentration of α-syn in human CSF was determined to be 2.1 ng/mL. A unique α-syn peptide, TVEGAGSIAAATGFVK (81-96), displayed excellent correlation with previous immunoassay results in two independent PD cohorts (p < 0.001), correlated with disease severity, and its changes significantly tracked the disease progression longitudinally. An MRM assay to quantify human CSF α-syn was developed and optimized. Sixty clinical samples from cross-sectional and longitudinal PD cohorts were analyzed with this approach. Although further larger scale validation is needed, the results suggest that α-syn peptide could serve as a promising biomarker in PD diagnosis and progression. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Li; Stewart, Tessandra; Shi, Min

    Aim: The alpha-synuclein (α-syn) level in human cerebrospinal fluid (CSF), as measured by immunoassays, is promising as a Parkinson’s disease (PD) biomarker. However, the levels of total α-syn are inconsistent among studies with large cohorts and different measurement platforms. Total α-syn level also does not correlate with disease severity or progression. Here, we developed a highly sensitive Multiple Reaction Monitoring (MRM) method to measure absolute CSF α-syn peptide concentrations without prior enrichment or fractionation, aiming to discover new candidate biomarkers. Results: Six peptides covering 73% of protein sequence were reliably identified, and two were consistently quantified in cross-sectional and longitudinalmore » cohorts. Absolute concentration of α-syn in human CSF was determined to be 2.1ng/mL. A unique α-syn peptide, TVEGAGSIAAATGFVK (81-96), displayed excellent correlation with previous immunoassay results in two independent PD cohorts (p < 0.001), correlated with disease severity, and its changes significantly tracked the disease progression longitudinally. Conclusions: An MRM assay to quantify human CSF α-syn was developed and optimized. Sixty clinical samples from cross-sectional and longitudinal PD cohorts were analyzed with this approach. Although further larger-scale validation is needed, the results suggest that α-syn peptide could serve as a promising biomarker in PD diagnosis and progression.« less

  8. A checklist of Chinese crickets (Orthoptera: Gryllidea).

    PubMed

    He, Zhu-Qing

    2018-01-07

    A checklist of Chinese crickets, including Taiwan, is offered. Presently 331 species or subspecies have been reported including true crickets, scale crickets, ant crickets and mole crickets belonging to 6 families, 16 subfamilies and 83 genera. Modicogryllus (Modicogryllus) maculatus (Shiraki, 1930) is moved to Comidoblemmus as C. maculatus (Shiraki, 1930) comb. nov. Velarifictorus (Velarifictorus) koshunensis (Shiraki, 1911) is moved to Turanogryllus as T. koshunensis (Shiraki, 1911) comb. nov. Qingryllus Chen Zheng, 1995 syn. is the junior synonym of Goniogryllus Chopard, 1936. Loxoblemmus angulatus Bey-Bienko, 1956 syn. is the junior synonym of Loxoblemmus appendicularis Shiraki, 1930. Cophogryllus kuhlgatzi Karny, 1908 syn. is the junior synonym of Teleogryllus (Brachyteleogryllus) occipitalis occipitalis (Serville, 1838). Velarifictorus (Velarifictorus) aspersus borealis Gorochov, 1985 syn. is the junior synonym of Velarifictorus (Velarifictorus) aspersus aspersus (Walker, 1869). Modicogryllus (Modicogryllus) latefasciatus (Chopard, 1933) syn. is the junior synonym of Velarifictorus (Velarifictorus) micado (Saussure, 1877). Velarifictorus (Velarifictorus) ornatus caudatus (Shiraki, 1930) syn. is the junior synonym of Velarifictorus (Velarifictorus) ornatus ornatus (Shiraki, 1911). Dianemobius nigrofasciatus (Matsumura, 1904) syn. is the junior synonym of Dianemobius fascipes (Walker, 1869). Polionemobius mikado (Shiraki, 1911) syn. is the junior synonym of Polionemobius taprobanensis (Walker, 1869). Vietacheta picea Gorochov, 1992, Oecanthus euryelytra Ichikawa, 2001, Oecanthus similator Ichikawa, 2001, Xabea levissima Gorochov, 1992, Pteronemobius (Pteronemobius) yezoensis (Shiraki, 1911), Metioche (Metioche) japonica (Ichikawa, 2001), Natula matsuurai Sugimoto, 2001 are the first records from China.

  9. DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Degui; Yu, Tianyu; Liu, Yongqiang

    Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenicmore » mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. - Highlights: • This study explore contribution of DNA damage to neurodegeneration in Parkinson's disease mice. • A53T-α-Syn MEF cells show a prolonged DNA damage repair process and senescense phenotype. • DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice. • DNA damage decrease the number of nigrostriatal dopaminergic neurons. • Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages.« less

  10. α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons.

    PubMed

    Zaltieri, Michela; Grigoletto, Jessica; Longhena, Francesca; Navarria, Laura; Favero, Gaia; Castrezzati, Stefania; Colivicchi, Maria Alessandra; Della Corte, Laura; Rezzani, Rita; Pizzi, Marina; Benfenati, Fabio; Spillantini, Maria Grazia; Missale, Cristina; Spano, PierFranco; Bellucci, Arianna

    2015-07-01

    The main neuropathological features of Parkinson's disease are dopaminergic nigrostriatal neuron degeneration, and intraneuronal and intraneuritic proteinaceous inclusions named Lewy bodies and Lewy neurites, respectively, which mainly contain α-synuclein (α-syn, also known as SNCA). The neuronal phosphoprotein synapsin III (also known as SYN3), is a pivotal regulator of dopamine neuron synaptic function. Here, we show that α-syn interacts with and modulates synapsin III. The absence of α-syn causes a selective increase and redistribution of synapsin III, and changes the organization of synaptic vesicle pools in dopamine neurons. In α-syn-null mice, the alterations of synapsin III induce an increased locomotor response to the stimulation of synapsin-dependent dopamine overflow, despite this, these mice show decreased basal and depolarization-dependent striatal dopamine release. Of note, synapsin III seems to be involved in α-syn aggregation, which also coaxes its increase and redistribution. Furthermore, synapsin III accumulates in the caudate and putamen of individuals with Parkinson's disease. These findings support a reciprocal modulatory interaction of α-syn and synapsin III in the regulation of dopamine neuron synaptic function. © 2015. Published by The Company of Biologists Ltd.

  11. Alpha-synuclein functions in the nucleus to protect against hydroxyurea-induced replication stress in yeast

    PubMed Central

    Liu, Xianpeng; Lee, Yong Joo; Liou, Liang-Chun; Ren, Qun; Zhang, Zhaojie; Wang, Shaoxiao; Witt, Stephan N.

    2011-01-01

    Hydroxyurea (HU) inhibits ribonucleotide reductase (RNR), which catalyzes the rate-limiting synthesis of deoxyribonucleotides for DNA replication. HU is used to treat HIV, sickle-cell anemia and some cancers. We found that, compared with vector control cells, low levels of alpha-synuclein (α-syn) protect S. cerevisiae cells from the growth inhibition and reactive oxygen species (ROS) accumulation induced by HU. Analysis of this effect using different α-syn mutants revealed that the α-syn protein functions in the nucleus and not the cytoplasm to modulate S-phase checkpoint responses: α-syn up-regulates histone acetylation and RNR levels, maintains helicase minichromosome maintenance protein complexes (Mcm2–7) on chromatin and inhibits HU-induced ROS accumulation. Strikingly, when residues 2–10 or 96–140 are deleted, this protective function of α-syn in the nucleus is abolished. Understanding the mechanism by which α-syn protects against HU could expand our knowledge of the normal function of this neuronal protein. PMID:21642386

  12. A systematic catalogue of butterflies of the former Soviet Union (Armenia, Azerbaijan, Belarus, Estonia, Georgia, Kyrgyzstan, Kazakhstan, Latvia, Lituania, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine, Uzbekistan) with special account to their type specimens (Lepidoptera: Hesperioidea, Papilionoidea).

    PubMed

    Korb, Stanislav K; Bolshakov, Lavr V

    2016-09-01

    comma repugnans (Staudinger, 1892) = lena Korshunov et Gorbunov, 1995, syn.n.; Argynnis niobe orientalis Alphéraky, 1881 =ornata Staudinger, 1901, syn.n. =tanjusha Zhdanko, 2011, syn.n.; Boloria frigga gibsoni (Barnes & Benjamin, 1926) = kosarevi Korb, 2011, syn.n., B. erubescens houri Wyatt, 1961 =ancilla Churkin, 2004, syn.n.; Melitaea fergana maracandica Staudinger, 1882 = irinae Churkin, Kolesnichenko et Tremasov, 2012, syn.n.; M. asteroida clara Staudinger, 1887 =ludmilla Churkin, Kolesnichenko et Tuzov, 2000, syn.n.; Paralasa jordana jordana (Staudinger, 1882) =khramovi Churkin et Pletnev, 2012, syn.n.; P. jordana subocellata (Staudinger, 1901) =kipnisi Churkin et Pletnev, 2012, syn.n.; P. kusnezovi kusnezovi (Avinov, 1910) =bosbutaensis Churkin et Pletnev, 2012, syn.n.; Erebia meta Staudinger, 1886 =gertha Staudinger, 1886, syn.n.; Oeneis ammon ammon Elwes, 1899 =smirnovi Yakovlev, 2011, syn.n.; O. norna tundra A.Bang-Haas, 1912 =ivonini Yakovlev, 2011, syn.n.; Chazara briseis ianthe (Pallas, 1771) =lyrnessus Fruhstorfer, 1908, syn.n., Plebejides stekolnikovi (Stradomsky et Tikhonov, 2015), comb.n.

  13. Loss of partitioning-defective-3/isotype-specific interacting protein (par-3/ASIP) in the elongating spermatid of RA175 (IGSF4A/SynCAM)-deficient mice.

    PubMed

    Fujita, Eriko; Tanabe, Yuko; Hirose, Tomonori; Aurrand-Lions, Michel; Kasahara, Tadashi; Imhof, Beat A; Ohno, Shigeo; Momoi, Takashi

    2007-12-01

    IGSF4a/RA175/SynCAM (RA175) and junctional adhesion molecules (Jams) are members of the immunoglobulin superfamily with a PDZ-binding domain at their C termini. Deficiency of Ra175 (Ra175(-/-)) as well as Jam-C deficiency (Jam-C(-/-)) causes the defect of the spermatid differentiation, oligo-astheno-teratozoospermia. Ra175(-/-) elongating spermatids fail to mature further, whereas Jam-C(-/-) round spermatids lose cell polarity, and most of Jam-C(-/-) elongated spermatids are completely lost. RA175 and Jam-C seem to have similar but distinct functional roles during spermatid differentiation. Here we show that the cell polarity protein Par-3 with PDZ domains, a binding partner of Jams, is one of the associated proteins of the cytoplasmic region of RA175 in testis. Par-3 and Jam-C are partly co-localized with RA175 in the elongating and elongated spermatids; their distributions overlapped with that of RA175 on the tips of the dorsal region of the head of the elongating spermatid (steps 9 to 12) in the wild type. In the Ra175(-/-) elongating spermatid, Par-3 was absent, and Jam-C was absent or abnormally localized. The RA175 formed a ternary complex with Jam-C via interaction with Par-3. The lack of the ternary complex in the Ra175(-/-) elongating spermatid may cause the defect of the specialized adhesion structures, resulting in the oligo-astheno-teratozoospermia.

  14. α-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons.

    PubMed

    Froula, Jessica M; Henderson, Benjamin W; Gonzalez, Jose Carlos; Vaden, Jada H; Mclean, John W; Wu, Yumei; Banumurthy, Gokulakrishna; Overstreet-Wadiche, Linda; Herskowitz, Jeremy H; Volpicelli-Daley, Laura A

    2018-05-01

    Neuronal inclusions composed of α-synuclein (α-syn) characterize Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Cognitive dysfunction defines DLB, and up to 80% of PD patients develop dementia. α-Syn inclusions are abundant in the hippocampus, yet functional consequences are unclear. To determine if pathologic α-syn causes neuronal defects, we induced endogenous α-syn to form inclusions resembling those found in diseased brains by treating hippocampal neurons with α-syn fibrils. At seven days after adding fibrils, α-syn inclusions are abundant in axons, but there is no cell death at this time point, allowing us to assess for potential alterations in neuronal function that are not caused by neuron death. We found that exposure of neurons to fibrils caused a significant reduction in mushroom spine densities, adding to the growing body of literature showing that altered spine morphology is a major pathologic phenotype in synucleinopathies. The reduction in spine densities occurred only in wild type neurons and not in neurons from α-syn knockout mice, suggesting that the changes in spine morphology result from fibril-induced corruption of endogenously expressed α-syn. Paradoxically, reduced postsynaptic spine density was accompanied by increased frequency of miniature excitatory postsynaptic currents (EPSCs) and presynaptic docked vesicles, suggesting enhanced presynaptic function. Action-potential dependent activity was unchanged, suggesting compensatory mechanisms responding to synaptic defects. Although activity at the level of the synapse was unchanged, neurons exposed to α-syn fibrils, showed reduced frequency and amplitudes of spontaneous Ca 2+ transients. These findings open areas of research to determine the mechanisms that alter neuronal function in brain regions critical for cognition at time points before neuron death.

  15. Synaptic Regulator α-Synuclein in Dopaminergic Fibers Is Essentially Required for the Maintenance of Subependymal Neural Stem Cells.

    PubMed

    Perez-Villalba, Ana; Sirerol-Piquer, M Salomé; Belenguer, Germán; Soriano-Cantón, Raúl; Muñoz-Manchado, Ana Belén; Villadiego, Javier; Alarcón-Arís, Diana; Soria, Federico N; Dehay, Benjamin; Bezard, Erwan; Vila, Miquel; Bortolozzi, Analía; Toledo-Aral, Juan José; Pérez-Sánchez, Francisco; Fariñas, Isabel

    2018-01-24

    Synaptic protein α-synuclein (α-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinson's disease. Here, we report that α-SYN present in dopaminergic nigral afferents is essential for the normal cycling and maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult male and female mice. We also show that premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking α-SYN resembles the effects of dopaminergic fiber degeneration resulting from chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine or intranigral inoculation of aggregated toxic α-SYN. Interestingly, NSC loss in α-SYN-deficient mice can be prevented by viral delivery of human α-SYN into their sustantia nigra or by treatment with l-DOPA, suggesting that α-SYN regulates dopamine availability to NSCs. Our data indicate that α-SYN, present in dopaminergic nerve terminals supplying the subependymal zone, acts as a niche component to sustain the neurogenic potential of adult NSCs and identify α-SYN and DA as potential targets to ameliorate neurogenic defects in the aging and diseased brain. SIGNIFICANCE STATEMENT We report an essential role for the protein α-synuclein present in dopaminergic nigral afferents in the regulation of adult neural stem cell maintenance, identifying the first synaptic regulator with an implication in stem cell niche biology. Although the exact role of α-synuclein in neural transmission is not completely clear, our results indicate that it is required for stemness and the preservation of neurogenic potential in concert with dopamine. Copyright © 2018 the authors 0270-6474/18/380815-12$15.00/0.

  16. Purification of α-Synuclein from Human Brain Reveals an Instability of Endogenous Multimers as the Protein Approaches Purity

    PubMed Central

    2015-01-01

    Despite two decades of research, the structure–function relationships of endogenous, physiological forms of α-synuclein (αSyn) are not well understood. Most in vitro studies of this Parkinson’s disease-related protein have focused on recombinant αSyn that is unfolded and monomeric, assuming that this represents its state in the normal human brain. Recently, we have provided evidence that αSyn exists in considerable part in neurons, erythrocytes, and other cells as a metastable multimer that principally sizes as a tetramer. In contrast to recombinant αSyn, physiological tetramers purified from human erythrocytes have substantial α-helical content and resist pathological aggregation into β-sheet rich fibers. Here, we report the first method to fully purify soluble αSyn from the most relevant source, human brain. We describe protocols that purify αSyn to homogeneity from nondiseased human cortex using ammonium sulfate precipitation, gel filtration, and ion exchange, hydrophobic interaction, and affinity chromatographies. Cross-linking of the starting material and the partially purified chromatographic fractions revealed abundant αSyn multimers, including apparent tetramers, but these were destabilized in large part to monomers during the final purification step. The method also fully purified the homologue β-synuclein, with a similar outcome. Circular dichroism spectroscopy showed that purified, brain-derived αSyn can display more helical content than the recombinant protein, but this result varied. Collectively, our data suggest that purifying αSyn to homogeneity destabilizes native, α-helix-rich multimers that exist in intact and partially purified brain samples. This finding suggests existence of a stabilizing cofactor (e.g., a small lipid) present inside neurons that is lost during final purification. PMID:25490121

  17. Specific pesticide-dependent increases in α-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines.

    PubMed

    Chorfa, Areski; Bétemps, Dominique; Morignat, Eric; Lazizzera, Corinne; Hogeveen, Kevin; Andrieu, Thibault; Baron, Thierry

    2013-06-01

    Epidemiological studies indicate a role of genetic and environmental factors in Parkinson's disease involving alterations of the neuronal α-synuclein (α-syn) protein. In particular, a relationship between Parkinson's disease and occupational exposure to pesticides has been repeatedly suggested. Our objective was to precisely assess changes in α-syn levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines following acute exposure to pesticides (rotenone, paraquat, maneb, and glyphosate) using Western blot and flow cytometry. These human cell lines express α-syn endogenously, and overexpression of α-syn (wild type or mutated A53T) can be obtained following recombinant adenoviral transduction. We found that endogenous α-syn levels in the SH-SY5Y neuroblastoma cell line were markedly increased by paraquat, and to a lesser extent by rotenone and maneb, but not by glyphosate. Rotenone also clearly increased endogenous α-syn levels in the SK-MEL-2 melanoma cell line. In the SH-SY5Y cell line, similar differences were observed in the α-syn adenovirus-transduced cells, with a higher increase of the A53T mutated protein. Paraquat markedly increased α-syn in the SK-MEL-2 adenovirus-transduced cell line, similarly for the wild-type or A53T proteins. The observed differences in the propensities of pesticides to increase α-syn levels are in agreement with numerous reports that indicate a potential role of exposure to certain pesticides in the development of Parkinson's disease. Our data support the hypothesis that pesticides can trigger some molecular events involved in this disease and also in malignant melanoma that consistently shows a significant but still unexplained association with Parkinson's disease.

  18. Large-Eddy Simulation of Internal Flow through Human Vocal Folds

    NASA Astrophysics Data System (ADS)

    Lasota, Martin; Šidlof, Petr

    2018-06-01

    The phonatory process occurs when air is expelled from the lungs through the glottis and the pressure drop causes flow-induced oscillations of the vocal folds. The flow fields created in phonation are highly unsteady and the coherent vortex structures are also generated. For accuracy it is essential to compute on humanlike computational domain and appropriate mathematical model. The work deals with numerical simulation of air flow within the space between plicae vocales and plicae vestibulares. In addition to the dynamic width of the rima glottidis, where the sound is generated, there are lateral ventriculus laryngis and sacculus laryngis included in the computational domain as well. The paper presents the results from OpenFOAM which are obtained with a large-eddy simulation using second-order finite volume discretization of incompressible Navier-Stokes equations. Large-eddy simulations with different subgrid scale models are executed on structured mesh. In these cases are used only the subgrid scale models which model turbulence via turbulent viscosity and Boussinesq approximation in subglottal and supraglottal area in larynx.

  19. Syn- and post-sedimentary controls on clay mineral assemblages in a tectonically active basin, Andean Argentinean foreland

    NASA Astrophysics Data System (ADS)

    Do Campo, Margarita; Nieto, Fernando; del Papa, Cecilia; Hongn, Fernando

    2014-07-01

    In the northern part of the Calchaquí Valley (NW Argentina), Palaeogene Andean foreland sediments are represented by a 1400-metre-thick continental succession (QLC: Quebrada de Los Colorados Formation) consisting of claystones, siltstones, sandstones, and conglomerates representing sedimentation in fluvial-alluvial plains and alluvial fan settings. To understand the main syn- and postsedimentary variables controlling the clay mineral assemblages of this succession, we have studied the fine-grained clastic sediments by X-ray diffraction and electron microscopy, along with a detailed sedimentary facies analysis, for two representative sections. In the northern section, the whole succession was sampled and analysed by XRD, whereas in the second section, a control point 15 km to the south, only the basal levels were analysed. The XRD study revealed a strong contrast in clay mineral assemblages between these two sections as well as with sections in the central Calchaquí Valley studied previously. In the northernmost part of the study area, a complete evolution from smectite at the top to R3 illite/smectite mixed-layers plus authigenic kaolinite at the bottom, through R1-type mixed-layers in between, has been recognized, indicating the attainment of late diagenesis. In contrast, the clay mineral assemblages of equivalent foreland sediments cropping out only 15 km to the south contain abundant smectite and micas, subordinate kaolinite and chlorite, and no I/S mixed-layers to the bottom of the sequence. Early diagenetic conditions were also inferred in a previous study for equivalent sediments of the QLC Formation cropping out to the south, in the central Calchaquí Valley, as smectite occurs in basal strata. Burial depths of approximately 3000 m were estimated for the QLC Formation in the central and northern Calchaquí Valley; in addition, an intermediate to slightly low geothermal gradient can be considered likely for both areas as foreland basins are regarded as

  20. Nomenclatural Studies Toward a World List of Diptera Genus-Group Names. Part IV: Charles Henry Tyler Townsend.

    PubMed

    Evenhuis, Neal L; Pont, Adrian C; Whitmore, Daniel

    2015-06-25

    ]; Eustomatodexia insulensis Townsend, 1892, n. stat. [Tachinidae].       The following genus-group names, not listed in previous regional catalogs, are treated here: Arabisca Townsend, 1935 [Sarcophagidae]; Eupeleteria Townsend, 1908 [Tachinidae]; Macropatelloa Townsend, 1931 [Tachinidae]; Neohypostena Townsend, 1915 [Tachinidae]; Neometapodia Townsend, 1892 [Sarcophagidae]; Tricyclopsis Townsend, 1916 [Calliphoridae]; Trongia Townsend, 1916 [Calliphoridae].        Previous First Reviser actions for multiple original spellings that were overlooked by other workers are given for the following: Genus-group names-Microchaetona Townsend, 1919 [Tachinidae]; Neopodomyia Townsend, 1927 [Tachinidae]; Opsophytopsis Townsend, 1918 [Sarcophagidae]; Prohypotachina Townsend, 1933 [Tachinidae]; Rhinomyodes Townsend, 1933 [Tachinidae]; Servilliodes Townsend, 1926 [Tachinidae]; Tephromyiella Townsend, 1918 [Sarcophagidae]; Thelairochaetona Townsend, 1919 [Tachinidae]; Xanthopteromyia Townsend, 1926 [Tachinidae]. Species-group names-Brachybelvosia brasiliensis Townsend, 1927 [Tachinidae]; Neocraspedothrix nova Townsend, 1927 [Tachinidae].        The following nominal genera enter into new synonymies: Bathytheresia Townsend, 1915 under Billaea Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Brachycoma Brauer & Bergenstamm, 1889 under Brachicoma Rondani, 1856, n. syn. [Sarcophagidae]; Chaetolyga Brauer, 1880 under Carcelia Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Chaetoprosopa Marschall, 1873 under Choeteprosopa Macquart, 1851, n. syn. [Tachinidae]; Chlororhynchomyia Senior-White, Aubertin & Smart, 1940 under Metallea Wulp, 1880, n. syn. [Rhiniidae]; Chrysomyia Macquart, 1835 under Chrysomya Robineau-Desvoidy, 1830, n. syn. [Calliphoridae]; Echinomyia Fischer von Waldheim, 1808 under Echinomya Latreille, 1805, n. syn. [Tachinidae]; Euhypochaetopsis Townsend, 1928 under Campylocheta Rondani, 1859, n. syn. [Tachinidae]; Graphomyia Macquart, 1834 under Graphomya Robineau

  1. In Situ Proximity Ligation Assay Reveals Co-Localization of Alpha-Synuclein and SNARE Proteins in Murine Primary Neurons.

    PubMed

    Almandoz-Gil, Leire; Persson, Emma; Lindström, Veronica; Ingelsson, Martin; Erlandsson, Anna; Bergström, Joakim

    2018-01-01

    The aggregation of alpha-synuclein (αSyn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of αSyn is to promote the soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between αSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA). Cortical primary neurons were cultured from either non-transgenic or transgenic mice expressing human αSyn with the A30P mutation under the Thy-1 promoter. With an antibody recognizing both mouse and human αSyn, a PLA signal indicating close proximity between αSyn and the three SNARE proteins was observed both in the soma and throughout the processes. No differences in the extent of PLA signals were seen between non-transgenic and transgenic neurons. With an antibody specific against human αSyn, the PLA signal was mostly located to the soma and was only present in a few cells. Taken together, in situ PLA is a method that can be used to investigate the co-localization of αSyn and the SNARE proteins in primary neuronal cultures.

  2. p27Kip1 regulates alpha-synuclein expression

    PubMed Central

    Gallastegui, Edurne; Domuro, Carla; Serratosa, Joan; Larrieux, Alejandra; Sin, Laura; Martinez, Jonatan; Besson, Arnaud; Morante-Redolat, José Manuel; Orlando, Serena; Aligue, Rosa; Fariñas, Isabel; Pujol, María Jesús; Bachs, Oriol

    2018-01-01

    Alpha-synuclein (α-SYN) is the main component of anomalous protein aggregates (Lewy bodies) that play a crucial role in several neurodegenerative diseases (synucleinopathies) like Parkinson’s disease and multiple system atrophy. However, the mechanisms involved in its transcriptional regulation are poorly understood. We investigated here the role of the cyclin-dependent kinase (Cdk) inhibitor and transcriptional regulator p27Kip1 (p27) in the regulation of α-SYN expression. We observed that selective deletion of p27 by CRISPR/Cas9 technology in neural cells resulted in increased levels of α-SYN. Knock-down of the member of the same family p21Cip1 (p21) also led to increased α-SYN levels, indicating that p27 and p21 collaborate in the repression of α-SYN transcription. We demonstrated that this repression is mediated by the transcription factor E2F4 and the member of the retinoblastoma protein family p130 and that it is dependent of Cdk activity. Chromatin immunoprecipitation analysis revealed specific binding sites for p27, p21 and E2F4 in the proximal α-SYN gene promoter. Finally, luciferase assays revealed a direct action of p27, p21 and E2F4 in α-SYN gene expression. Our findings reveal for the first time a negative regulatory mechanism of α-SYN expression, suggesting a putative role for cell cycle regulators in the etiology of synucleinopathies. PMID:29662651

  3. Phospholipase D1 downregulation by α-synuclein: Implications for neurodegeneration in Parkinson's disease.

    PubMed

    Conde, Melisa A; Alza, Natalia P; Iglesias González, Pablo A; Scodelaro Bilbao, Paola G; Sánchez Campos, Sofía; Uranga, Romina M; Salvador, Gabriela A

    2018-06-01

    We have previously shown that phospholipase D (PLD) pathways have a role in neuronal degeneration; in particular, we found that PLD activation is associated with synaptic injury induced by oxidative stress. In the present study, we investigated the effect of α-synuclein (α-syn) overexpression on PLD signaling. Wild Type (WT) α-syn was found to trigger the inhibition of PLD1 expression as well as a decrease in ERK1/2 phosphorylation and expression levels. Moreover, ERK1/2 subcellular localization was shown to be modulated by WT α-syn in a PLD1-dependent manner. Indeed, PLD1 inhibition was found to alter the neurofilament network and F-actin distribution regardless of the presence of WT α-syn. In line with this, neuroblastoma cells expressing WT α-syn exhibited a degenerative-like phenotype characterized by a marked reduction in neurofilament light subunit (NFL) expression and the rearrangement of the F-actin organization, compared with either the untransfected or the empty vector-transfected cells. The gain of function of PLD1 through the overexpression of its active form had the effect of restoring NFL expression in WT α-syn neurons. Taken together, our findings reveal an unforeseen role for α-syn in PLD regulation: PLD1 downregulation may constitute an early mechanism in the initial stages of WT α-syn-triggered neurodegeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Enrichment of anaerobic syngas-converting bacteria from thermophilic bioreactor sludge.

    PubMed

    Alves, Joana I; Stams, Alfons J M; Plugge, Caroline M; Alves, M Madalena; Sousa, Diana Z

    2013-12-01

    Thermophilic (55 °C) anaerobic microbial communities were enriched with a synthetic syngas mixture (composed of CO, H2 , and CO2 ) or with CO alone. Cultures T-Syn and T-CO were incubated and successively transferred with syngas (16 transfers) or CO (9 transfers), respectively, with increasing CO partial pressures from 0.09 to 0.88 bar. Culture T-Syn, after 4 successive transfers with syngas, was also incubated with CO and subsequently transferred (9 transfers) with solely this substrate - cultures T-Syn-CO. Incubation with syngas and CO caused a rapid decrease in the microbial diversity of the anaerobic consortium. T-Syn and T-Syn-CO showed identical microbial composition and were dominated by Desulfotomaculum and Caloribacterium species. Incubation initiated with CO resulted in the enrichment of bacteria from the genera Thermincola and Thermoanaerobacter. Methane was detected in the first two to three transfers of T-Syn, but production ceased afterward. Acetate was the main product formed by T-Syn and T-Syn-CO. Enriched T-CO cultures showed a two-phase conversion, in which H2 was formed first and then converted to acetate. This research provides insight into how thermophilic anaerobic communities develop using syngas/CO as sole energy and carbon source can be steered for specific end products and subsequent microbial synthesis of chemicals. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  5. Endoparasites of rodents from the Chittagong Hill Tracts in Southeastern Bangladesh.

    PubMed

    Fuehrer, Hans-Peter; Baumann, Timo A; Riedl, Julia; Treiber, Moritz; Igel, Petra; Swoboda, Paul; Joachim, Anja; Noedl, Harald

    2012-11-01

    Rodents are a key mammalian group highly successful in adapting to a variety of environments throughout the world and play an important role in many zoonotic cycles. Within this project, the gastrointestinal and extraintestinal parasite fauna of 76 rodents (Muroidea and Sciuridae) was determined in the District of Bandarban (Chittagong Hill Tracts) in Southeastern Bangladesh. Gastrointestinal and extraintestinal parasites were examined with macro- and microscopical tools (e.g. Ziehl-Neelsen Staining) at a field site in Bandarban. A wide variety of parasites were found in rodent hosts, including protozoa-Giardia sp. (n = 8), Cryptosporidium sp. (n = 1), Entamoeba sp. (n = 8), Trichomonadida (n = 4), Isospora sp. (n = 1), trematodes (Echinostoma sp.; n = 3), cestodes-Hymenolepis nana (n = 1), Hymenolepis diminuta (n = 3), Hymenolepis sp. (n = 2), Taenia taeniaeformis-Larven (n = 4), Catenotaenia sp. (n = 1), Taenia sp. (n = 1), nematodes-Heterakis spumosa (n = 4), Heterakis sp. (n = 1), Aspiculuris tetraptera (n = 2), Capillaria hepatica (n = 2), Capillaria sp. (n = 3), Syphacia sp. (n = 2), Strongyloides sp. (n = 10), Trichostrongylus sp. (n = 2) and Trichuris sp. (n = 1)-and acanthocephalans (Moniliformis moniliformis; n = 2). Several of the examined parasites are of zoonotic importance via direct or indirect transmission (e.g. C. hepatica) and may affect humans.

  6. Prevalence and diversity of gastrointestinal helminths in free-ranging Asian house shrew (Suncus murinus) in Bangladesh

    PubMed Central

    Rahman, Mizanur; Islam, Shariful; Masuduzzaman, Md.; Alam, Mahabub; Chawdhury, Mohammad Nizam Uddin; Ferdous, Jinnat; Islam, Md. Nurul; Hassan, Mohammad Mahmudul; Hossain, Mohammad Alamgir; Islam, Ariful

    2018-01-01

    Background and Aim Asian house shrew (Suncus murinus), a widely distributed small mammal in the South Asian region, can carry helminths of zoonotic importance. The aim of the study was to know the prevalence and diversity of gastrointestinal (GI) helminths in free-ranging Asian house shrew (S. murinus) in Bangladesh. Materials and Methods A total of 86 Asian house shrews were captured from forest areas and other habitats of Bangladesh in 2015. Gross examination of the whole GI tract was performed for gross helminth detection, and coproscopy was done for identification of specific eggs or larvae. Results The overall prevalence of GI helminth was 77.9% (67/86), with six species including nematodes (3), cestodes (2), and trematodes (1). Of the detected helminths, the dominant parasitic group was from the genus Hymenolepis spp.(59%), followed by Strongyloides spp.(17%), Capillaria spp. (10%), Physaloptera spp. (3%), and Echinostoma spp.(3%). Conclusion The finding shows that the presence of potential zoonotic parasites (Hymenolepis spp. and Capillaria spp.) in Asian house shrew is ubiquitous in all types of habitat (forest land, cropland and dwelling) in Bangladesh. Therefore, further investigation is crucial to examine their role in the transmission of human helminthiasis. PMID:29805224

  7. Generation of a neurodegenerative disease mouse model using lentiviral vectors carrying an enhanced synapsin I promoter.

    PubMed

    Matsuzaki, Yasunori; Oue, Miho; Hirai, Hirokazu

    2014-02-15

    Certain inherited progressive neurodegenerative disorders, such as spinocerebellar ataxia (SCA), affect neurons in large areas of the central nervous system (CNS). The selective expression of disease-causing and therapeutic genes in susceptible regions and cell types is critical for the generation of animal models and development of gene therapies for these diseases. Previous studies have demonstrated the advantages of the short synapsin I (SynI) promoter (0.5 kb) as a neuron-specific promoter for robust transgene expression. However, the short SynI promoter has also shown some promoter activity in glia and a lack of transgene expression in significant areas of the CNS. New methods: To improve the SynI promoter, we used a SynI promoter that is twice as long (1.0 kb) as the short SynI promoter and incorporated a minimal CMV (minCMV) sequence. We observed that the 1.0 kb rat SynI promoter with minCMV [rSynI(1.0)-minCMV] exhibited robust promoter strength, excellent neuronal specificity and wide-ranging transgene expression throughout the CNS. Comparison with existing methods: Compared with the two previously reported short (0.5 kb) promoters, the new promoter was superior with respect to neuronal specificity and more efficiently transduced neurons. Moreover, transgenic mice expressing the mutant protein ATXN1[Q98], which causes SCA type 1 (SCA1), under the control of the rSynI(1.0)-minCMV promoter showed robust transgene expression specifically in neurons throughout the CNS and exhibited progressive ataxia. rSynI(1.0)-minCMV drives robust and neuron-specific transgene expression throughout the CNS and is therefore useful for viral vector-mediated neuron-specific gene delivery and generation of neuron-specific transgenic animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Clinical Validation of Multiplex Real-Time PCR Assays for Detection of Bacterial Meningitis Pathogens

    PubMed Central

    Theodore, M. Jordan; Mair, Raydel; Trujillo-Lopez, Elizabeth; du Plessis, Mignon; Wolter, Nicole; Baughman, Andrew L.; Hatcher, Cynthia; Vuong, Jeni; Lott, Lisa; von Gottberg, Anne; Sacchi, Claudio; McDonald, J. Matthew; Messonnier, Nancy E.; Mayer, Leonard W.

    2012-01-01

    Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae are important causes of meningitis and other infections, and rapid, sensitive, and specific laboratory assays are critical for effective public health interventions. Singleplex real-time PCR assays have been developed to detect N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA and serogroup-specific genes in the cap locus for N. meningitidis serogroups A, B, C, W135, X, and Y. However, the assay sensitivity for serogroups B, W135, and Y is low. We aimed to improve assay sensitivity and develop multiplex assays to reduce time and cost. New singleplex real-time PCR assays for serogroup B synD, W135 synG, and Y synF showed 100% specificity for detecting N. meningitidis species, with high sensitivity (serogroup B synD, 99% [75/76]; W135 synG, 97% [38/39]; and Y synF, 100% [66/66]). The lower limits of detection (LLD) were 9, 43, and 10 copies/reaction for serogroup B synD, W135 synG, and Y synF assays, respectively, a significant improvement compared to results for the previous singleplex assays. We developed three multiplex real-time PCR assays for detection of (i) N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA (NHS assay); (ii) N. meningitidis serogroups A, W135, and X (AWX assay); and (iii) N. meningitidis serogroups B, C, and Y (BCY assay). Each multiplex assay was 100% specific for detecting its target organisms or serogroups, and the LLD was similar to that for the singleplex assay. Pairwise comparison of real-time PCR between multiplex and singleplex assays showed that cycle threshold values of the multiplex assay were similar to those for the singleplex assay. There were no substantial differences in sensitivity and specificity between these multiplex and singleplex real-time PCR assays. PMID:22170919

  9. The small heat shock proteins αB-crystallin (HSPB5) and Hsp27 (HSPB1) inhibit the intracellular aggregation of α-synuclein.

    PubMed

    Cox, Dezerae; Ecroyd, Heath

    2017-07-01

    Protein homeostasis, or proteostasis, is the process of maintaining the conformational and functional integrity of the proteome. Proteostasis is preserved in the face of stress by a complex network of cellular machinery, including the small heat shock molecular chaperone proteins (sHsps), which act to inhibit the aggregation and deposition of misfolded protein intermediates. Despite this, the pathogenesis of several neurodegenerative diseases has been inextricably linked with the amyloid fibrillar aggregation and deposition of α-synuclein (α-syn). The sHsps are potent inhibitors of α-syn aggregation in vitro. However, the limited availability of a robust, cell-based model of α-syn aggregation has, thus far, restricted evaluation of sHsp efficacy in the cellular context. As such, this work sought to establish a robust model of intracellular α-syn aggregation using Neuro-2a cells. Aggregation of α-syn was found to be sensitive to inhibition of autophagy and the proteasome, resulting in a significant increase in the proportion of cells containing α-syn inclusions. This model was then used to evaluate the capacity of the sHsps, αB-c and Hsp27, to prevent α-syn aggregation in cells. To do so, we used bicistronic expression plasmids to express the sHsps. Unlike traditional fluorescent fusion constructs, these bicistronic expression plasmids enable only individual transfected cells expressing the sHsps (via expression of the fluorescent reporter) to be analysed, but without the need to tag the sHsp, which can affect its oligomeric structure and chaperone activity. Overexpression of both αB-c and Hsp27 significantly reduced the intracellular aggregation of α-syn. Thus, these findings suggest that overexpressing or boosting the activity of sHsps may be a way of preventing amyloid fibrillar aggregation of α-syn in the context of neurodegenerative disease.

  10. Clinical validation of multiplex real-time PCR assays for detection of bacterial meningitis pathogens.

    PubMed

    Wang, Xin; Theodore, M Jordan; Mair, Raydel; Trujillo-Lopez, Elizabeth; du Plessis, Mignon; Wolter, Nicole; Baughman, Andrew L; Hatcher, Cynthia; Vuong, Jeni; Lott, Lisa; von Gottberg, Anne; Sacchi, Claudio; McDonald, J Matthew; Messonnier, Nancy E; Mayer, Leonard W

    2012-03-01

    Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae are important causes of meningitis and other infections, and rapid, sensitive, and specific laboratory assays are critical for effective public health interventions. Singleplex real-time PCR assays have been developed to detect N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA and serogroup-specific genes in the cap locus for N. meningitidis serogroups A, B, C, W135, X, and Y. However, the assay sensitivity for serogroups B, W135, and Y is low. We aimed to improve assay sensitivity and develop multiplex assays to reduce time and cost. New singleplex real-time PCR assays for serogroup B synD, W135 synG, and Y synF showed 100% specificity for detecting N. meningitidis species, with high sensitivity (serogroup B synD, 99% [75/76]; W135 synG, 97% [38/39]; and Y synF, 100% [66/66]). The lower limits of detection (LLD) were 9, 43, and 10 copies/reaction for serogroup B synD, W135 synG, and Y synF assays, respectively, a significant improvement compared to results for the previous singleplex assays. We developed three multiplex real-time PCR assays for detection of (i) N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA (NHS assay); (ii) N. meningitidis serogroups A, W135, and X (AWX assay); and (iii) N. meningitidis serogroups B, C, and Y (BCY assay). Each multiplex assay was 100% specific for detecting its target organisms or serogroups, and the LLD was similar to that for the singleplex assay. Pairwise comparison of real-time PCR between multiplex and singleplex assays showed that cycle threshold values of the multiplex assay were similar to those for the singleplex assay. There were no substantial differences in sensitivity and specificity between these multiplex and singleplex real-time PCR assays.

  11. Crystal structure and magnetic properties of two isomeric three-dimensional pyromellitate-containing cobalt(II) complexes.

    PubMed

    Fabelo, Oscar; Pasán, Jorge; Cañadillas-Delgado, Laura; Delgado, Fernando S; Lloret, Francesc; Julve, Miguel; Ruiz-Pérez, Catalina

    2008-09-15

    The hydrothermal preparation, crystal structure determination, and magnetic study of two isomers made up of 1,2,4,5-benzenetetracarboxylate and high-spin Co(II) ions of formula [Co2(bta)(H2O)4]n x 2n H2O (1 and 2; H4bta = 1,2,4,5-benzenetetracarboxylic acid) are reported. 1 and 2 are three-dimensional compounds whose structures can be described as (4,4) rectangular layers of trans-diaquacobalt(II) units with the bta(4-) anion acting as tetrakis-monodentate ligand through the four carboxylate groups, which are further connected through other trans-[Co(H2O)2](2+) (1) and planar [Co(H2O)4](2+) (2) entities, with the bridging units being a carboxylate group in either the anti-syn (1) or syn-syn (2) conformations and a water molecule (2). The study of the magnetic properties of 1 and 2 in the temperature range 1.9-300 K shows the occurrence of weak antiferromagnetic interactions between the high-spin Co(II) ions, with the strong decrease of chi(M)T upon cooling being mainly due to the depopulation of the higher energy Kramers doublets of the six-coordinated Co(II) ions. The computed values of the exchange coupling between the Co(II) ions across anti-syn carboxylate (1) and syn-syn carboxylate/water (2) bridges are J = -0.060 (1) and -1.90 (2) cm(-1) (with the Hamiltonian being defined as H = -Jsigma(i,j)S(i) x S(j)). These values follow the different conformations of the carboxylate bridge in 1 (anti-syn) and 2 (syn-syn) with the occurrence of a double bridge in 2 (water/carboxylate).

  12. Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.

    PubMed

    Llorens, Franc; Kruse, Niels; Karch, André; Schmitz, Matthias; Zafar, Saima; Gotzmann, Nadine; Sun, Ting; Köchy, Silja; Knipper, Tobias; Cramm, Maria; Golanska, Ewa; Sikorska, Beata; Liberski, Pawel P; Sánchez-Valle, Raquel; Fischer, Andre; Mollenhauer, Brit; Zerr, Inga

    2018-03-01

    The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range. Quantification of CSF α-synuclein (a-syn) by an in-house ECL-based ELISA assay has been recently reported as an excellent approach for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), the most prevalent form of human prion disease. In the present study, we validated a commercially available ECL-based a-syn ELISA platform as a diagnostic test for correct classification of sCJD cases. CSF a-syn was analysed in 203 sCJD cases with definite diagnosis and in 445 non-CJD cases. We investigated reproducibility and stability of CSF a-syn and made recommendations for its analysis in the sCJD diagnostic workup. A sensitivity of 98% and a specificity of 97% were achieved when using an optimal cut-off of 820 pg/mL a-syn. Moreover, we were able to show a negative correlation between a-syn levels and disease duration suggesting that CSF a-syn may be a good prognostic marker for sCJD patients. The present study validates the use of a-syn as a CSF biomarker of sCJD and establishes the clinical and pre-analytical parameters for its use in differential diagnosis in clinical routine. Additionally, the current test presents some advantages compared to other diagnostic approaches: it is fast, economic, requires minimal amount of CSF and a-syn levels are stable along disease progression.

  13. Chemical Compensation of Mitochondrial Phospholipid Depletion in Yeast and Animal Models of Parkinson’s Disease

    PubMed Central

    Wang, Shaoxiao; Zhang, Siyuan; Xu, Chuan; Barron, Addie; Galiano, Floyd; Patel, Dhaval; Lee, Yong Joo; Caldwell, Guy A.; Caldwell, Kim A.

    2016-01-01

    We have been investigating the role that phosphatidylethanolamine (PE) and phosphatidylcholine (PC) content plays in modulating the solubility of the Parkinson’s disease protein alpha-synuclein (α-syn) using Saccharomyces cerevisiae and Caenorhabditis elegans. One enzyme that synthesizes PE is the conserved enzyme phosphatidylserine decarboxylase (Psd1/yeast; PSD-1/worms), which is lodged in the inner mitochondrial membrane. We previously found that decreasing the level of PE due to knockdown of Psd1/psd-1 affects the homeostasis of α-syn in vivo. In S. cerevisiae, the co-occurrence of low PE and α-syn in psd1Δ cells triggers mitochondrial defects, stress in the endoplasmic reticulum, misprocessing of glycosylphosphatidylinositol-anchored proteins, and a 3-fold increase in the level of α-syn. The goal of this study was to identify drugs that rescue this phenotype. We screened the Prestwick library of 1121 Food and Drug Administration-approved drugs using psd1Δ + α-syn cells and identified cyclosporin A, meclofenoxate hydrochloride, and sulfaphenazole as putative protective compounds. The protective activity of these drugs was corroborated using C. elegans in which α-syn is expressed specifically in the dopaminergic neurons, with psd-1 depleted by RNAi. Worm populations were examined for dopaminergic neuron survival following psd-1 knockdown. Exposure to cyclosporine, meclofenoxate, and sulfaphenazole significantly enhanced survival at day 7 in α-syn-expressing worm populations whereby 50–55% of the populations displayed normal neurons, compared to only 10–15% of untreated animals. We also found that all three drugs rescued worms expressing α-syn in dopaminergic neurons that were deficient in the phospholipid cardiolipin following cardiolipin synthase (crls-1) depletion by RNAi. We discuss how these drugs might block α-syn pathology in dopaminergic neurons. PMID:27736935

  14. An Overview on the Role of α -Synuclein in Experimental Models of Parkinson's Disease from Pathogenesis to Therapeutics.

    PubMed

    Javed, Hayate; Kamal, Mohammad Amjad; Ojha, Shreesh

    2016-01-01

    Parkinson's disease (PD) is a devastating and progressive movement disorder characterized by symptoms of muscles rigidity, tremor, postural instability and slow physical movements. Biochemically, PD is characterized by lack of dopamine production and its action due to loss of dopaminergic neurons and neuropathologically by the presence of intracytoplasmic inclusions known as Lewy bodies, which mainly consist of presynaptic neuronal protein, α-synuclein (α-syn). It is believed that alteration in α-syn homeostasis leads to increased accumulation and aggregation of α-syn in Lewy body. Based on the important role of α-syn from pathogenesis to therapeutics, the recent researches are mainly focused on deciphering the critical role of α-syn at advanced level. Being a major protein in Lewy body that has a key role in pathogenesis of PD, several model systems including immortalized cell lines (SH-SY5Y), primary neuronal cultures, yeast (saccharomyces cerevisiae), drosophila (fruit flies), nematodes (Caenorhabditis elegans) and rodents are being employed to understand the PD pathogenesis and treatment. In order to study the etiopathogensis and develop novel therapeutic target for α -syn aggregation, majority of investigators rely on toxin (rotenone, 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine, 6-hydroxydopamine, paraquat)-induced animal models of PD as a tool for basic research. Whereas, cell and tissue based models are mostly utilized to elucidate the mechanistic and molecular pathways underlying the α -syn induced toxicity and therapeutic approaches in PD. Gene modified mouse models based on α-syn expression are fascinating for modeling familial PD and toxin induced models provide a suitable approach for sporadic PD. The purpose of this review is to provide a summary and a critical review of the involvement of α-syn in various in vitro and in vivo models of PD based on use of neurotoxins as well as genetic modifications.

  15. JOINTS AND SYN-SEDIMENTARY FAULTS NETWORKS IN MARINE CLAYS AND MUDSTONES. Importance for Radwaste storage

    NASA Astrophysics Data System (ADS)

    Arnould, M.

    2009-12-01

    There is a number of marine clays, mudstones, marls, 100 to 200 m thick, showing smectites, mixed layers illite/smectite, with a small percentage of organic matter and sulphides with a variable clay, silt, and carbonate content. I published (Arnould , 2006) examples from Lower Cambrian to Miocene in age and from the Baltic shore to Spain in Europe. Observations were made mostly in quarries and pits down to more than 40 m and in underground research laboratories (URL). Only visible on fresh cuts amongst a variety of fissures there is always a network of joints. Schematically one family is the bedding (horizontal) the two others are normal to the bedding and orthogonal between them. The orientations of vertical joints are different from the orientations of pits and quarries’s walls. The networks are intrinsic. It was first well described by Skempton & al (1969) in Eocene London Clay. Joints are matt in texture, clean, without filling or cement. The order of magnitude of their linear dimensions is decimeter to meter. It is necessary to start from the original sediment: mud. Deposited in flakes mud has a bee’s nest microscopic structure. Each nest is full of water. Hence mud may have a water content up to 300%, reported to its dry weight. Paradoxically mud is impervious. As proposed by Cosgrove (2001) progressive but discontinuous hydraulic fracturing could be the origin of vertical joints, with drainage upwards and compaction of the sediment. Geological observations show that ioints are formed during the sedimentation process. There is also a world literature concluding at the necessary early fracturing of mudstones and marls hosts of sand dykes. Very few faults are identified in field observations and on exploration logs. But it is obvious that drainage and compaction of mud over thousands square kilometers induced differential settlements with many syn-sedimentary non tectonic faults constituting another discontinuity network. These faults inside the same

  16. α-synuclein assemblies sequester neuronal α3-Na+/K+-ATPase and impair Na+ gradient

    PubMed Central

    Shrivastava, Amulya Nidhi; Redeker, Virginie; Fritz, Nicolas; Pieri, Laura; Almeida, Leandro G; Spolidoro, Maria; Liebmann, Thomas; Bousset, Luc; Renner, Marianne; Léna, Clément; Aperia, Anita; Melki, Ronald; Triller, Antoine

    2015-01-01

    Extracellular α-synuclein (α-syn) assemblies can be up-taken by neurons; however, their interaction with the plasma membrane and proteins has not been studied specifically. Here we demonstrate that α-syn assemblies form clusters within the plasma membrane of neurons. Using a proteomic-based approach, we identify the α3-subunit of Na+/K+-ATPase (NKA) as a cell surface partner of α-syn assemblies. The interaction strength depended on the state of α-syn, fibrils being the strongest, oligomers weak, and monomers none. Mutations within the neuron-specific α3-subunit are linked to rapid-onset dystonia Parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). We show that freely diffusing α3-NKA are trapped within α-syn clusters resulting in α3-NKA redistribution and formation of larger nanoclusters. This creates regions within the plasma membrane with reduced local densities of α3-NKA, thereby decreasing the efficiency of Na+ extrusion following stimulus. Thus, interactions of α3-NKA with extracellular α-syn assemblies reduce its pumping activity as its mutations in RDP/AHC. PMID:26323479

  17. Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein.

    PubMed

    Makky, Ali; Bousset, Luc; Polesel-Maris, Jérôme; Melki, Ronald

    2016-11-30

    Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson's disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs. The latter exhibited differences in their shape, their structure but also in their functional properties. We have conducted an AFM study at high resolution and performed a statistical analysis of fibrillar α-Syn shape and thermal fluctuations to calculate the persistence length to further assess the nanomechanical properties of α-Syn polymorphs. Herein, we demonstrated quantitatively that distinct polymorphs made of the same protein (wild-type α-Syn) show significant differences in their morphology (height, width and periodicity) and physical properties (persistence length, bending rigidity and axial Young's modulus).

  18. Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein

    PubMed Central

    Makky, Ali; Bousset, Luc; Polesel-Maris, Jérôme; Melki, Ronald

    2016-01-01

    Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson’s disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs. The latter exhibited differences in their shape, their structure but also in their functional properties. We have conducted an AFM study at high resolution and performed a statistical analysis of fibrillar α-Syn shape and thermal fluctuations to calculate the persistence length to further assess the nanomechanical properties of α-Syn polymorphs. Herein, we demonstrated quantitatively that distinct polymorphs made of the same protein (wild-type α-Syn) show significant differences in their morphology (height, width and periodicity) and physical properties (persistence length, bending rigidity and axial Young’s modulus). PMID:27901068

  19. Novel Benzothiazole Derivatives as Fluorescent Probes for Detection of β-Amyloid and α-Synuclein Aggregates.

    PubMed

    Watanabe, Hiroyuki; Ono, Masahiro; Ariyoshi, Taisuke; Katayanagi, Rikako; Saji, Hideo

    2017-08-16

    Deposits of β-amyloid (Aβ) and α-synuclein (α-syn) are the hallmark of Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. The detection of these protein aggregates with fluorescent probes is particularly of interest for preclinical studies using fluorescence microscopy on human brain tissue. In this study, we newly designed and synthesized three push-pull benzothiazole (PP-BTA) derivatives as fluorescent probes for detection of Aβ and α-syn aggregates. Fluorescence intensity of all PP-BTA derivatives significantly increased upon binding to Aβ(1-42) and α-syn aggregates in solution. In in vitro saturation binding assays, PP-BTA derivatives demonstrated affinity for both Aβ(1-42) (K d = 40-148 nM) and α-syn (K d = 48-353 nM) aggregates. In particular, PP-BTA-4 clearly stained senile plaques composed of Aβ aggregates in the AD brain section. Moreover, it also labeled Lewy bodies composed of α-syn aggregates in the PD brain section. These results suggest that PP-BTA-4 may serve as a promising fluorescent probe for the detection of Aβ and α-syn aggregates.

  20. Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein

    NASA Astrophysics Data System (ADS)

    Makky, Ali; Bousset, Luc; Polesel-Maris, Jérôme; Melki, Ronald

    2016-11-01

    Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson’s disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs. The latter exhibited differences in their shape, their structure but also in their functional properties. We have conducted an AFM study at high resolution and performed a statistical analysis of fibrillar α-Syn shape and thermal fluctuations to calculate the persistence length to further assess the nanomechanical properties of α-Syn polymorphs. Herein, we demonstrated quantitatively that distinct polymorphs made of the same protein (wild-type α-Syn) show significant differences in their morphology (height, width and periodicity) and physical properties (persistence length, bending rigidity and axial Young’s modulus).

  1. Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity

    PubMed Central

    Jha, Narendra Nath; Ghosh, Dhiman; Das, Subhadeep; Anoop, Arunagiri; Jacob, Reeba S.; Singh, Pradeep K.; Ayyagari, Narasimham; Namboothiri, Irishi N. N.; Maji, Samir K.

    2016-01-01

    Alpha-synuclein (α-Syn) aggregation into oligomers and fibrils is associated with dopaminergic neuron loss occurring in Parkinson’s disease (PD) pathogenesis. Compounds that modulate α-Syn aggregation and interact with preformed fibrils/oligomers and convert them to less toxic species could have promising applications in the drug development efforts against PD. Curcumin is one of the Asian food ingredient which showed promising role as therapeutic agent against many neurological disorders including PD. However, the instability and low solubility makes it less attractive for the drug development. In this work, we selected various curcumin analogs and studied their toxicity, stability and efficacy to interact with different α-Syn species and modulation of their toxicity. We found a subset of curcumin analogs with higher stability and showed that curcumin and its various analogs interact with preformed fibrils and oligomers and accelerate α-Syn aggregation to produce morphologically different amyloid fibrils in vitro. Furthermore, these curcumin analogs showed differential binding with the preformed α-Syn aggregates. The present data suggest the potential role of curcumin analogs in modulating α-Syn aggregation. PMID:27338805

  2. Taxonomic revision of Afrotropical Laccophilus Leach, 1815 (Coleoptera, Dytiscidae)

    PubMed Central

    Biström, Olof; Nilsson, Anders N.; Bergsten, Johannes

    2015-01-01

    follows: Laccophilus continentalis Gschwendtner, 1935 = Laccophilus perplexus Omer-Cooper, 1970, syn. n., Laccophilus taeniolatus Régimbart, 1889 = Laccophilus congener Omer-Cooper, 1957, syn. n., Laccophilus adspersus Boheman, 1848 = Laccophilus vitshumbii Guignot, 1959, syn. n. = Laccophilus adspersus nigeriensis Omer-Cooper, 1970, syn. n. = Laccophilus adspersus sudanensis Omer-Cooper, 1970, syn. n., Laccophilus modestus Régimbart, 1895 = Laccophilus espanyoli Hernando, 1990, syn. n., Laccophilus flaveolus Régimbart, 1906 = Laccophilus pampinatus Guignot, 1941, syn. n., Laccophilus trilineola Régimbart, 1889 = Laccophilus simulator Omer-Cooper, 1958, syn. n., Laccophilus mediocris Guignot, 1952 = Laccophilus meii Rocchi, 2000, syn. n., Laccophilus epinephes Guignot, 1955 = Laccophilus castaneus Guignot, 1956, syn. n., Laccophilus saegeri Guignot, 1958 = Laccophilus comoensis Pederzani & Reintjes, 2002, syn. n., Laccophilus restrictus Sharp, 1882 = Laccophilus evanescens Régimbart, 1895, syn. n., Laccophilus incrassatus Gschwendtner, 1933 = Laccophilus virgatus Guignot, 1953, syn. n., Laccophilus cyclopis Sharp, 1882 = Laccophilus shephardi Omer-Cooper, 1965, syn. n., Laccophilus burgeoni Gschwendtner, 1930 = Laccophilus wittei Guignot, 1952, syn. n., Laccophilus secundus Régimbart, 1895 = Laccophilus torquatus Guignot, 1956, syn. n., Laccophilus desintegratus Régimbart, 1895 = Laccophilus sanguinosus Régimbart, 1895, syn. n. and Laccophilus flavopictus Régimbart, 1889 = Laccophilus bergeri Guignot, 1953, syn. n. = Laccophilus segmentatus Omer-Cooper, 1957, syn. n. Lectotypes are designated for the following taxa: Laccophilus productus Régimbart, 1906, Laccophilus ruficollis Zimmermann, 1919, Laccophilus sordidus Sharp, 1882, Laccophilus alluaudi Régimbart, 1899, Laccophilus pictipennis Sharp, 1882, Laccophilus wehnckei Sharp, 1882, Laccophilus continentalis Gschwendtner, 1935, Laccophilus simplicistriatus Gschwendtner, 1932, Laccophilus complicatus Sharp

  3. Spine Topographical Distribution of Skin α-Synuclein Deposits in Idiopathic Parkinson Disease.

    PubMed

    Donadio, Vincenzo; Incensi, Alex; Rizzo, Giovanni; Scaglione, Cesa; Capellari, Sabina; Fileccia, Enrico; Avoni, Patrizia; Liguori, Rocco

    2017-05-01

    Phosphorylated α-synuclein (p-syn) in skin nerves mainly in the proximal sites is a promising neurodegenerative biomarker for idiopathic Parkinson disease (IPD). However, the p-syn spine distribution particularly in patients with unilateral motor dysfunctions remains undefined. This study aimed to investigate in IPD p-syn differences between left and right cervical spine sites in patients with prevalent unilateral motor symptoms, and cervical and thoracic spine sites in patients with bilateral motor symptoms. We enrolled 28 IPD patients fulfilling clinical diagnostic criteria associated with abnormal nigro-striatal DatScan and cardiac MIBG: 15 with prevalently unilateral motor symptoms demonstrated by DatScan; 13 with bilateral motor symptoms and DatScan abnormalities. Patients underwent skin biopsy searching for intraneural p-syn deposits: skin samples were taken from C7 paravertebral left and right sites in unilateral patients and from cervical (C7) and thoracic (Th12) paravertebral spine regions in bilateral patients. Unilateral patients displayed 20% of abnormal p-syn deposits in the affected motor site, 60% in both sites and 20% only in the non-affected site. P-syn was found in all patients in C7 but in only 62% of patients in Th12. Our data showed that cervical p-syn deposits displayed a uniform distribution between both sides not following the motor dysfunction in unilateral patients, and skin nerve p-syn deposits demonstrated a spine gradient with the cervical site expressing the highest positivity. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  4. c-Abl phosphorylates α-synuclein and regulates its degradation: implication for α-synuclein clearance and contribution to the pathogenesis of Parkinson's disease

    PubMed Central

    Mahul-Mellier, Anne-Laure; Fauvet, Bruno; Gysbers, Amanda; Dikiy, Igor; Oueslati, Abid; Georgeon, Sandrine; Lamontanara, Allan J.; Bisquertt, Alejandro; Eliezer, David; Masliah, Eliezer; Halliday, Glenda; Hantschel, Oliver; Lashuel, Hilal A.

    2014-01-01

    Increasing evidence suggests that the c-Abl protein tyrosine kinase could play a role in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. c-Abl has been shown to regulate the degradation of two proteins implicated in the pathogenesis of PD, parkin and α-synuclein (α-syn). The inhibition of parkin's neuroprotective functions is regulated by c-Abl-mediated phosphorylation of parkin. However, the molecular mechanisms by which c-Abl activity regulates α-syn toxicity and clearance remain unknown. Herein, using NMR spectroscopy, mass spectrometry, in vitro enzymatic assays and cell-based studies, we established that α-syn is a bona fide substrate for c-Abl. In vitro studies demonstrate that c-Abl directly interacts with α-syn and catalyzes its phosphorylation mainly at tyrosine 39 (pY39) and to a lesser extent at tyrosine 125 (pY125). Analysis of human brain tissues showed that pY39 α-syn is detected in the brains of healthy individuals and those with PD. However, only c-Abl protein levels were found to be upregulated in PD brains. Interestingly, nilotinib, a specific inhibitor of c-Abl kinase activity, induces α-syn protein degradation via the autophagy and proteasome pathways, whereas the overexpression of α-syn in the rat midbrains enhances c-Abl expression. Together, these data suggest that changes in c-Abl expression, activation and/or c-Abl-mediated phosphorylation of Y39 play a role in regulating α-syn clearance and contribute to the pathogenesis of PD. PMID:24412932

  5. Fluoxetine Ameliorates Behavioral and Neuropathological Deficits in a Transgenic Model Mouse of α-synucleinopathy

    PubMed Central

    Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Patrick, Christina; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; May, Verena; Winkler, Juergen; Masliah, Eliezer

    2013-01-01

    The term α-synucleinopathies refers to a group of age-related neurological disorders including Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) that display an abnormal accumulation of alpha-synuclein (α-syn). In contrast to the neuronal α-syn accumulation observed in PD and DLB, MSA is characterized by a widespread oligodendrocytic α-syn accumulation. Transgenic mice expressing human α-syn under the oligodendrocyte-specific myelin basic protein promoter (MBP1-hαsyn tg mice) model many of the behavioral and neuropathological alterations observed in MSA. Fluoxetine, a selective serotonin reuptake inhibitor, has been shown to be protective in toxin-induced models of PD, however its effects in an in vivo transgenic model of α-synucleinopathy remain unclear. In this context, this study examined the effect of fluoxetine in the MBP1-hαsyn tg mice, a model of MSA. Fluoxetine adminstration ameliorated motor deficits in the MBP1-hαsyn tg mice, with a concomitant decrease in neurodegenerative pathology in the basal ganglia, neocortex and hippocampus. Fluoxetine adminstration also increased levels of the neurotrophic factors, GDNF (glial-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) in the MBP1-hαsyn tg mice compared to vehicle-treated tg mice. This fluoxetine-induced increase in GDNF and BDNF protein levels was accompanied by activation of the ERK signaling pathway. The effects of fluoxetine adminstration on myelin and serotonin markers were also examined. Collectively these results indicate that fluoxetine may represent a novel therapeutic intervention for MSA and other neurodegenerative disorders. PMID:22281106

  6. A low molecular weight protein tyrosine phosphatase from Synechocystis sp. strain PCC 6803: enzymatic characterization and identification of its potential substrates

    PubMed Central

    Mukhopadhyay, Archana; Kennelly, Peter J.

    2011-01-01

    The predicted protein product of open reading frame slr0328 from Synechocystis sp. PCC 6803, SynPTP, possesses significant amino acid sequence similarity with known low molecular weight protein tyrosine phosphatases (PTPs). To determine the functional properties of this hypothetical protein, open reading frame slr0328 was expressed in Escherichia coli. The purified recombinant protein, SynPTP, displayed its catalytic phosphatase activity towards several tyrosine, but not serine, phosphorylated exogenous protein substrates. The protein phosphatase activity of SynPTP was inhibited by sodium orthovanadate, a known inhibitor of tyrosine phosphatases, but not by okadaic acid, an inhibitor for many serine/threonine phosphatases. Kinetic analysis indicated that the Km and Vmax values for SynPTP towards p-nitrophenyl phosphate are similar to those of other known bacterial low molecular weight PTPs. Mutagenic alteration of the predicted catalytic cysteine of PTP, Cys7, to serine abolished enzyme activity. Using a combination of immunodetection, mass spectrometric analysis and mutagenically altered Cys7SerAsp125Ala-SynPTP, we identified PsaD (photosystem I subunit II), CpcD (phycocyanin rod linker protein) and phycocyanin-α and -β subunits as possible endogenous substrates of SynPTP in this cyanobacterium. These results indicate that SynPTP might be involved in the regulation of photosynthesis in Synechocystis sp. PCC 6803. PMID:21288886

  7. New species and distributional records of Aleocharinae (Coleoptera, Staphylinidae) from Ontario, Canada, with a checklist of recorded species

    PubMed Central

    Brunke, Adam J.; Klimaszewski, Jan; Dorval, Julie-Anne; Bourdon, Caroline; Paiero, Steven M.; Marshall, Stephen A.

    2012-01-01

    Abstract The Aleocharinae (Coleoptera: Staphylinidae) of Ontario were reviewed in the context of recently studied material, primarily from insect surveys conducted by the University of Guelph Insect Collection (Ontario, Canada). Aleochara daviesi Klimaszewski & Brunke sp. n., Agaricomorpha websteri Klimaszewski & Brunke sp. n., Atheta (Microdota) alesi Klimaszewski & Brunke sp. n., Dinaraea backusensis Klimaszewski & Brunke sp. n., and Strigota obscurata Klimaszewski & Brunke sp. n. are described as new to science. We also report 47 new Ontario records and 24 new Canadian records. Callicerus rigidicornis (Erichson) and Alevonota gracilenta (Erichson) are newly reported from North America as adventive species. A checklist, with Canadian distributions by province, of the 224 species of Aleocharinae known from Ontario is given. The following species are placed in subjective synonymy with Dexiogyia angustiventris (Casey): (Dexiogyia asperata (Casey) syn. n., Dexiogyia abscissa (Casey) syn. n., Dexiogyia tenuicauda (Casey) syn. n., Dexiogyia intenta (Casey) syn. n., Dexiogyia alticola (Casey) syn. n.). The following species are placed in subjective synonymy with Acrotona subpygmaea (Bernhauer): (Acrotona avia (Casey) syn. n., Acrotona puritana (Casey) syn. n.). Lectotypes are designated for Thiasophila angustiventris Casey, Thiasophila asperata Casey, Ischnoglossa intenta Casey, Oxypoda rubescans Casey, Chilopora americana Casey, Chilopora fuliginosa Casey, Coprothassa smithi Casey, Atheta subpygmaea Bernhauer, Colpodota puritana Casey, Strigota seducens Casey, Trichiusa compacta Casey, Trichiusa hirsuta Casey and Trichiusa robustula Casey. PMID:22577320

  8. α-synuclein transfer through tunneling nanotubes occurs in SH-SY5Y cells and primary brain pericytes from Parkinson’s disease patients

    PubMed Central

    Dieriks, Birger Victor; Park, Thomas I-H.; Fourie, Chantelle; Faull, Richard L. M.; Dragunow, Mike; Curtis, Maurice A.

    2017-01-01

    Parkinson’s disease (PD) is characterized by the presence of inclusions known as Lewy bodies, which mainly consist of α-synuclein (α-syn) aggregates. There is growing evidence that α-syn self-propagates in non-neuronal cells, thereby contributing to the progression and spread of PD pathology in the brain. Tunneling nanotubes (TNTs) are long, thin, F-actin-based membranous channels that connect cells and have been proposed to act as conduits for α-syn transfer between cells. SH-SY5Y cells and primary human brain pericytes, derived from postmortem PD brains, frequently form TNTs that allow α-syn transfer and long-distance electrical coupling between cells. Pericytes in situ contain α-syn precipitates like those seen in neurons. Exchange through TNTs was rapid, but dependent on the size of the protein. Proteins were able to spread throughout a network of cells connected by TNTs. Transfer through TNTs was not restricted to α-syn; fluorescent control proteins and labeled membrane were also exchanged through TNTs. Most importantly the formation of TNTs and transfer continued during mitosis. Together, our results provide a detailed description of TNTs in SH-SY5Y cells and human brain PD pericytes, demonstrating their role in α-syn transfer and further emphasize the importance that non-neuronal cells, such as pericytes play in disease progression. PMID:28230073

  9. Parkinson disease and progressive supranuclear palsy: protein expression in skin.

    PubMed

    Rodríguez-Leyva, Ildefonso; Chi-Ahumada, Erika G; Carrizales, Juan; Rodríguez-Violante, Mayela; Velázquez-Osuna, Salvador; Medina-Mier, Verónica; Martel-Gallegos, María G; Zarazúa, Sergio; Enríquez-Macías, Lourdes; Castro, Adriana; Calderón-Garcidueñas, Ana Laura; Jiménez-Capdeville, María E

    2016-03-01

    This study characterizes the expression of tau (p-tau) and α-synuclein (α-syn) by immunohistochemistry in the skin of three different populations: healthy control (HC), Parkinson disease (PD), and progressive supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker that could differentiate between subjects with PD and PSP. We evaluated the presence of p-tau and α-syn in a pilot study in the skin of three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and 10 patients with PSP. Four millimeters punch biopsies were obtained from the occipital area and analyzed by immunohistochemistry using antibodies against α-syn and phosphorylated species of tau. PHF (paired helical filaments) antibody identifies p-tau in both normal and pathological conditions and AT8 recognizes p-tau characteristic of pathological conditions. Differences between the three groups were assessed by quantification of immunopositive areas in the epidermis. The immunopositivity pattern of p-tau and α-syn was significantly different among the three groups. Healthy subjects showed minimal staining using AT8 and α-syn. The PD group showed significantly higher α-syn and AT8 immunopositivity, while the PSP group only expressed higher AT8 immunopositivity than HCs. These data suggest that the skin reflects brain pathology. Therefore, immunohistochemical analysis of p-tau and α-syn in the skin can be useful for further characterization of PD and PSP.

  10. Common structural features of toxic intermediates from α-synuclein and GroES fibrillogenesis detected using cryogenic coherent X-ray diffraction imaging.

    PubMed

    Kameda, Hiroshi; Usugi, Sayaka; Kobayashi, Mana; Fukui, Naoya; Lee, Seki; Hongo, Kunihiro; Mizobata, Tomohiro; Sekiguchi, Yuki; Masaki, Yu; Kobayashi, Amane; Oroguchi, Tomotaka; Nakasako, Masayoshi; Takayama, Yuki; Yamamoto, Masaki; Kawata, Yasushi

    2017-01-01

    The aggregation and deposition of α-synuclein (αSyn) in neuronal cells is correlated to pathogenesis of Parkinson's disease. Although the mechanism of αSyn aggregation and fibril formation has been studied extensively, the structural hallmarks that are directly responsible for toxicity toward cells are still under debate. Here, we have compared the structural characteristics of the toxic intermediate molecular species of αSyn and similar toxic species of another protein, GroES, using coherent X-ray diffraction analysis. Using coherent X-ray free electron laser pulses of SACLA, we analysed αSyn and GroES fibril intermediate species and characterized various aggregate structures. Unlike previous studies where an annular oligomeric form of αSyn was identified, particle reconstruction from scattering traces suggested that the specific forms of the toxic particles were varied, with the sizes of the particles falling within a specific range. We did however discover a common structural feature in both αSyn and GroES samples; the edges of the detected particles were nearly parallel and produced a characteristic diffraction pattern in the diffraction experiments. The presence of parallel-edged particles in toxic intermediates of αSyn and GroES fibrillogenesis pointed towards a plausible common molecular interface that leads to the formation of mature fibrils. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  11. Loss of Partitioning-Defective-3/Isotype-Specific Interacting Protein (Par-3/ASIP) in the Elongating Spermatid of RA175 (IGSF4A/SynCAM)-Deficient Mice

    PubMed Central

    Fujita, Eriko; Tanabe, Yuko; Hirose, Tomonori; Aurrand-Lions, Michel; Kasahara, Tadashi; Imhof, Beat A.; Ohno, Shigeo; Momoi, Takashi

    2007-01-01

    IGSF4a/RA175/SynCAM (RA175) and junctional adhesion molecules (Jams) are members of the immunoglobulin superfamily with a PDZ-binding domain at their C termini. Deficiency of Ra175 (Ra175−/−) as well as Jam-C deficiency (Jam-C−/−) causes the defect of the spermatid differentiation, oligo-astheno-teratozoospermia. Ra175−/− elongating spermatids fail to mature further, whereas Jam-C−/− round spermatids lose cell polarity, and most of Jam-C−/− elongated spermatids are completely lost. RA175 and Jam-C seem to have similar but distinct functional roles during spermatid differentiation. Here we show that the cell polarity protein Par-3 with PDZ domains, a binding partner of Jams, is one of the associated proteins of the cytoplasmic region of RA175 in testis. Par-3 and Jam-C are partly co-localized with RA175 in the elongating and elongated spermatids; their distributions overlapped with that of RA175 on the tips of the dorsal region of the head of the elongating spermatid (steps 9 to 12) in the wild type. In the Ra175−/− elongating spermatid, Par-3 was absent, and Jam-C was absent or abnormally localized. The RA175 formed a ternary complex with Jam-C via interaction with Par-3. The lack of the ternary complex in the Ra175−/− elongating spermatid may cause the defect of the specialized adhesion structures, resulting in the oligo-astheno-teratozoospermia. PMID:18055550

  12. Dosimetric evaluation of magnetic resonance-generated synthetic CT for radiation treatment of rectal cancer.

    PubMed

    Wang, Hesheng; Du, Kevin; Qu, Juliet; Chandarana, Hersh; Das, Indra J

    2018-01-01

    The purpose of this study was to assess the dosimetric equivalence of magnetic resonance (MR)-generated synthetic CT (synCT) and simulation CT for treatment planning in radiotherapy of rectal cancer. This study was conducted on eleven patients who underwent whole-body PET/MR and PET/CT examination in a prospective IRB-approved study. For each patient synCT was generated from Dixon MR using a model-based method. Standard treatment planning directives were used to create a four-field box (4F), an oblique four-field (O4F) and a volumetric modulated arc therapy (VMAT) plan on synCT for treatment of rectal cancer. The plans were recalculated on CT with the same monitor units (MUs) as that of synCT. Dose-volume metrics of planning target volume (PTV) and organs at risk (OARs) as well as gamma analysis of dose distributions were evaluated to quantify the difference between synCT and CT plans. All plans were calculated using the analytical anisotropic algorithm (AAA). The VMAT plans on synCT and CT were also calculated using the Acuros XB algorithm for comparison with the AAA calculation. Medians of absolute differences in PTV metrics between synCT and CT plans were 0.2%, 0.2% and 0.3% for 4F, O4F and VMAT respectively. No significant differences were observed in OAR dose metrics including bladder V40Gy, mean dose in bladder, bowel V45Gy and femoral head V30Gy in any techniques. Gamma analysis with 2%/2mm dose difference/distance to agreement criteria showed median passing rates of 99.8% (range: 98.5 to 100%), 99.9% (97.2 to 100%), and 99.9% (99.4 to 100%) for 4F, O4F and VMAT, respectively. Using Acuros XB dose calculation, 2%/2mm gamma analysis generated a passing rate of 99.2% (97.7 to 99.9%) for VMAT plans. SynCT enabled dose calculation equivalent to conventional CT for treatment planning of 3D conformal treatment as well as VMAT of rectal cancer. The dosimetric agreement between synCT and CT calculated doses demonstrated the potential of MR-only treatment planning

  13. Dietary intake and the development of the metabolic syndrome: the Atherosclerosis Risk in Communities study.

    PubMed

    Lutsey, Pamela L; Steffen, Lyn M; Stevens, June

    2008-02-12

    The role of diet in the origin of metabolic syndrome (MetSyn) is not well understood; thus, we sought to evaluate the relationship between incident MetSyn and dietary intake using prospective data from 9514 participants (age, 45 to 64 years) enrolled in the Atherosclerosis Risk in Communities (ARIC) study. Dietary intake was assessed at baseline via a 66-item food frequency questionnaire. We used principal-components analysis to derive "Western" and "prudent" dietary patterns from 32 food groups and evaluated 10 food groups used in previous studies of the ARIC cohort. MetSyn was defined by American Heart Association guidelines. Proportional-hazards regression was used. Over 9 years of follow-up, 3782 incident cases of MetSyn were identified. After adjustment for demographic factors, smoking, physical activity, and energy intake, consumption of a Western dietary pattern (P(trend)=0.03) was adversely associated with incident MetSyn. After further adjustment for intake of meat, dairy, fruits and vegetables, refined grains, and whole grains, analysis of individual food groups revealed that meat (P(trend)<0.001), fried foods (P(trend)=0.02), and diet soda (P(trend)=< 0.001) also were adversely associated with incident MetSyn, whereas dairy consumption (P(trend)=0.006) was beneficial. No associations were observed between incident MetSyn and a prudent dietary pattern or intakes of whole grains, refined grains, fruits and vegetables, nuts, coffee, or sweetened beverages. These prospective findings suggest that consumption of a Western dietary pattern, meat, and fried foods promotes the incidence of MetSyn, whereas dairy consumption provides some protection. The diet soda association was not hypothesized and deserves further study.

  14. Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy.

    PubMed

    Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Patrick, Christina; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; May, Verena; Winkler, Juergen; Masliah, Eliezer

    2012-04-01

    The term α-synucleinopathies refers to a group of age-related neurological disorders including Parkinson's disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) that display an abnormal accumulation of alpha-synuclein (α-syn). In contrast to the neuronal α-syn accumulation observed in PD and DLB, MSA is characterized by a widespread oligodendrocytic α-syn accumulation. Transgenic mice expressing human α-syn under the oligodendrocyte-specific myelin basic protein promoter (MBP1-hαsyn tg mice) model many of the behavioral and neuropathological alterations observed in MSA. Fluoxetine, a selective serotonin reuptake inhibitor, has been shown to be protective in toxin-induced models of PD, however its effects in an in vivo transgenic model of α-synucleinopathy remain unclear. In this context, this study examined the effect of fluoxetine in the MBP1-hαsyn tg mice, a model of MSA. Fluoxetine administration ameliorated motor deficits in the MBP1-hαsyn tg mice, with a concomitant decrease in neurodegenerative pathology in the basal ganglia, neocortex and hippocampus. Fluoxetine administration also increased levels of the neurotrophic factors, GDNF (glial-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) in the MBP1-hαsyn tg mice compared to vehicle-treated tg mice. This fluoxetine-induced increase in GDNF and BDNF protein levels was accompanied by activation of the ERK signaling pathway. The effects of fluoxetine administration on myelin and serotonin markers were also examined. Collectively these results indicate that fluoxetine may represent a novel therapeutic intervention for MSA and other neurodegenerative disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Revision of the types of male Sciaridae (Diptera) described from Australia by F.A.A. Skuse.

    PubMed

    Broadley, Adam; Kauschke, Ellen; Mohrig, Werner

    2016-11-17

    A total of 27 male sciarid types described by Skuse (1888 and 1890), held in the Australian National Insect Collection, Canberra, and the Australian Museum, Sydney, were remounted and examined microscopically. Of these, 25 species were described as Sciara Meigen, one as Zygoneura Meigen and one as Trichosia Winnertz. Revision of these species revealed the following: 13 species belong to the genus Bradysia Winnertz (B. amabilis, B. conjuncta, B. crassicornis, B. exsequialis, B. frequens, B. froggatti, B. luctifica, B. maesta, B. mastersi, B. ornatula, B. pernitida, B. pictipes, B. unica), 1 species to the genus Corynoptera Winnertz (C. minutela), 4 species to the genus Austrosciara Schmitz & Mjöberg (Aus. infrequens, Aus. montivaga, Aus. spectabilis, Aus. winnertzi), 2 species to the genus Pseudolycoriella Menzel & Mohrig (Psl. cavatica, Psl. ignobilis), 1 species to the genus Pseudozygomma Mohrig (Pseudoz. maculipennis), 1 species to the genus Sciara Meigen (Sc. tryoni), and 1 species to the genus Scythropochroa Enderlein (Scyth. macleayi). In total 26 species were new combinations. Eight species names were declared as new synonyms: Bradysia pictipes (Skuse, 1888) = Sciara notata Skuse, 1888 syn. n. and = Bradysia seticornis Vilkamaa, Hippa & Mohrig, 2012 (from New Caledonia) syn. n.; Bradysia conjuncta (Skuse, 1890) = Sciara serenipennis Skuse, 1890 syn. n.; Pseudolycoriella cavatica (Skuse, 1888) = Sciara familiaris Skuse, 1888 syn. n. and = Sciara festiva Skuse, 1888 syn. n.; Bradysia luctifica (Skuse, 1888) = Bradysia planistylata Vilkamaa, Hippa & Mohrig, 2012 syn. n.; Sciara tryoni Skuse, 1890 = Sciara insulana Vilkamaa, Hippa & Mohrig, 2015 syn. n. (both species are from New Caledonia); Austrosciara winnertzi (Skuse, 1888) = Sciara rufulenta Edwards, 1927 syn. n. (from New Zealand). Lectotype specimens were designated for 17 species in order to fix the names.

  16. The Effect of Fragmented Pathogenic α-Synuclein Seeds on Prion-like Propagation*

    PubMed Central

    Tarutani, Airi; Suzuki, Genjiro; Shimozawa, Aki; Nonaka, Takashi; Akiyama, Haruhiko; Hisanaga, Shin-ichi; Hasegawa, Masato

    2016-01-01

    Aggregates of abnormal proteins are widely observed in neuronal and glial cells of patients with various neurodegenerative diseases, and it has been proposed that prion-like behavior of these proteins can account for not only the onset but also the progression of these diseases. However, it is not yet clear which abnormal protein structures function most efficiently as seeds for prion-like propagation. In this study, we aimed to identify the most pathogenic species of α-synuclein (α-syn), the main component of the Lewy bodies and Lewy neurites that are observed in α-synucleinopathies. We prepared various forms of α-syn protein and examined their seeding properties in vitro in cells and in mouse experimental models. We also characterized these α-syn species by means of electron microscopy and thioflavin fluorescence assays and found that fragmented β sheet-rich fibrous structures of α-syn with a length of 50 nm or less are the most efficient promoters of accumulation of phosphorylated α-syn, which is the hallmark of α-synucleinopathies. These results indicate that fragmented amyloid-like aggregates of short α-syn fibrils are the key pathogenic seeds that trigger prion-like conversion. PMID:27382062

  17. Revision of the Gonioctena nivosa species-group (Coleoptera, Chrysomelidae, Chrysomelinae) in the Holarctic region, with descriptions of two new species

    PubMed Central

    Cho, Hee-Wook; Kippenberg, Horst; Borowiec, Lech

    2016-01-01

    Abstract The Gonioctena nivosa species-group of the genus Gonioctena Chevrolat, 1836 is defined and reviewed. It contains six species including two new to science: Gonioctena gracilicornis (Kraatz, 1879), Gonioctena nivosa (Suffrian, 1851), Gonioctena norvegica (Strand, 1936), Gonioctena springlovae (Bechyně, 1948), Gonioctena amurensis Cho & Borowiec, sp. n. and Gonioctena jani Cho & Borowiec, sp. n. Six new synonyms are proposed: Gonioctena nivosa (= Gonioctena arctica alberta Brown, 1952, syn. n., Phytodecta linnaeana bergrothi Jacobson, 1901, syn. n., Phytodecta linnaeanus var. mutatus Achard, 1924, syn. n., Phytodecta linnaeanus var. simplex Achard, 1924, syn. n. and Phytodecta nivosa var. cedehensis Ronchetti, 1922, syn. n.) and Gonioctena norvegica (= Gonioctena janovskii Medvedev, 1976, syn. n.). Phytodecta flavicornis var. limbatipennis Achard, 1924 and Phytodecta nivosa var. bicolor Heyden, 1883 are removed from synonymy with Gonioctena nivosa (Suffrian, 1851) and are synonymized with Gonioctena flavicornis (Suffrian, 1851). Distribution maps, a key to species, color variation, geographic variation of male genitalia and host plants are provided. Ovoviviparity is newly recorded in Gonioctena gracilicornis and Gonioctena nivosa. Lectotypes are designated for Gonioctena affinis, Gonioctena arctica, Gonioctena linnaeana bergrothi and Gonioctena nivosa. PMID:27408579

  18. [Critical test of the activity of tetramisole phosphate on gastrointestinal helminths of sheep].

    PubMed

    Oba, M S; Mello, E de B; Dell'Porto, A; Soares, M A; Schumaker, T T

    1979-01-01

    The phosphate sale of tetramizol assayed in naturally infested sheep by subcutaneous infection at the dosis of 8,66 mg/kg revealed very high efficiency against strongylid gastro-intestinal nematodes; its efficiency was comparable that found by several authors for the hydrochloride and cyclamate salts of the same drug, also by subcutaneious injection, at the dosis of 10 mg/kg. In what concerns helminths belonging to the genera Strongyloides and Capillaria our results were not conclusive enough.

  19. [Helminth eggs: trace elements of neolithic and paleolithic parasitosis on French sites].

    PubMed

    Bouchet, F

    1997-01-01

    On the neolithic site of Chalain (Jura, France), the analysis of human coprolites has revealed the presence of many well preserved eggs of Helminths: eggs of Trichuris spP., Capillaria spp., Fasciola hepatica, Diphyllobothrium spP. In the paleolithic picturial sanctuary of the Grande Grotte at Arcy-sur-Cure (Yonne, France), eggs of Ascaris spP. have been discovered. The presence of these parasits open a new way of search about the knowledge of ancient populations.

  20. Stereodivergent catalytic doubly diastereoselective nitroaldol reactions using heterobimetallic complexes.

    PubMed

    Sohtome, Yoshihiro; Kato, Yuko; Handa, Shinya; Aoyama, Naohiro; Nagawa, Keita; Matsunaga, Shigeki; Shibasaki, Masakatsu

    2008-06-05

    Stereodivergent construction of three contiguous stereocenters in catalytic doubly diastereoselective nitroaldol reactions of alpha-chiral aldehydes with nitroacetaldehyde dimethyl acetal using two types of heterobimetallic catalysts is described. A La-Li-BINOL (LLB) catalyst afforded anti,syn-nitroaldol products in >20:1-14:1 selectivity, and a Pd/La/Schiff base catalyst afforded complimentary syn,syn-nitroaldol products in 10:1-5:1 selectivity.

  1. α-Synuclein Activates Innate Immunity but Suppresses Interferon-γ Expression in Murine Astrocytes.

    PubMed

    Wang, Jintang; Chen, Zheng; Walston, Jeremy; Gao, Peisong; Gao, Maolong; Leng, Sean X

    2018-05-19

    Glial activation and neuroinflammation contribute to pathogenesis of neurodegenerative diseases, linked to neuron loss and dysfunction. α-Synuclein (α-syn), as a metabolite of neuron, can induce microglia activation to trigger innate immune response. However, whether α-syn, as well as its mutants (A53T, A30P and E46K), induces astrocyte activation and inflammatory response is not fully elucidated. In this study, we used A53T mutant and wildtype α-syns to stimulate primary astrocytes in dose- and time-dependent manners (0.5, 2, 8 and 20 μg/mL for 24 hour or 3, 12, 24 and 48 hour at 2 μg/mL), and evaluated activation of several canonical inflammatory pathway components. The results showed that A53T mutant or wildtype α-syn significantly upregulated mRNA expression of toll-like receptor (TLR)2, TLR3, nuclear factor-κB and interleukin (IL)-1β, displaying a pattern of positive dose-effect correlation or negative time-effect correlation. Such upregulation was confirmed at protein levels of TLR2 (at 20 μg/mL), TLR3 (at most doses) and IL-1β (at 3 hour) by western blotting. Blockage of TLR2 other than TLR4 inhibited TLR3 and IL-1β mRNA expressions. By contrast, interferon (IFN)-γ was significantly downregulated at mRNA, protein and protein release levels, especially at high concentrations of α-syns or early time-points. These findings indicate that α-syn was a TLRs-mediated immunogenic agent (A53T mutant stronger than wildtype α-syn). The stimulation patterns suggest that persistent release and accumulation of α-syn is required for maintenance of innate immunity activation, and IFN-γ expression inhibition by α-syn suggests a novel immune molecule interaction mechanism underlying pathogenesis of neurodegenerative diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. The interplay of intrinsic disorder and macromolecular crowding on α-synuclein fibril formation

    NASA Astrophysics Data System (ADS)

    Shirai, Nobu C.; Kikuchi, Macoto

    2016-02-01

    α-synuclein (α-syn) is an intrinsically disordered protein which is considered to be one of the causes of Parkinson's disease. This protein forms amyloid fibrils when in a highly concentrated solution. The fibril formation of α-syn is induced not only by increases in α-syn concentration but also by macromolecular crowding. In order to investigate the coupled effect of the intrinsic disorder of α-syn and macromolecular crowding, we construct a lattice gas model of α-syn in contact with a crowding agent reservoir based on statistical mechanics. The main assumption is that α-syn can be expressed as coarse-grained particles with internal states coupled with effective volume; and disordered states are modeled by larger particles with larger internal entropy than other states. Thanks to the simplicity of the model, we can exactly calculate the number of conformations of crowding agents, and this enables us to prove that the original grand canonical ensemble with a crowding agent reservoir is mathematically equivalent to a canonical ensemble without crowding agents. In this expression, the effect of macromolecular crowding is absorbed in the internal entropy of disordered states; it is clearly shown that the crowding effect reduces the internal entropy. Based on Monte Carlo simulation, we provide scenarios of crowding-induced fibril formation. We also discuss the recent controversy over the existence of helically folded tetramers of α-syn, and suggest that macromolecular crowding is the key to resolving the controversy.

  3. Synthetic biology in the German press: how implications of metaphors shape representations of morality and responsibility.

    PubMed

    Döring, Martin

    2018-06-24

    Synthetic biology (SynBio) represents a relatively young field of research which has developed into an important scientific endeavour. Characterised by a high degree of interdisciplinary work crossing disciplinary boundaries, such as biology, mathematics and engineering, SynBio has been, since its beginning, devoted to creating new biological functions, metabolic pathways or even minimal organisms. Although its often-articulated aim of developing new forms of life has so far not been archived, SynBio nowadays represents a well-established biotechnological approach and it has also attracted public concern, especially since Craig Venter's work on Mycoplasma Mycoides JCVI-syn1.0. Taking these developments as a starting point, the paper empirically investigates the metaphorical representations of SynBio in two leading German media publications, the daily newspaper Die Frankfurter Allgemeine Zeitung and the weekly magazine Der Spiegel between 2000 and 2010. Using a novel combination of metaphor and co-occurrence analysis, the paper engages in a systematic examination of implicit moral implications inherent in linguistic images permeating this news coverage. It demonstrates a method of how media-metaphorical representations and their moral implications of SynBio could analytically be revealed and analysed. In doing so, it aims at contributing to empirical ethical analyses of the news coverage on SynBio in particular and offers an approach that methodologically adds to literature on responsible language use, which is emerging in science and technology studies and ethical analyses of new technologies.

  4. SU-G-JeP2-08: Image-Guided Radiation Therapy Using Synthetic CTs in Brain Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Price, R.G.; Glide-Hurst, C.; Henry Ford Health System, Detroit, MI

    Purpose: Synthetic-CTs(synCTs) are essential for MR-only treatment planning. However, the performance of synCT for IGRT must be carefully assessed. This work evaluated the accuracy of synCT and synCT-generated DRRs and determined their performance for IGRT in brain cancer radiation therapy. Methods: MR-SIM and CT-SIM images were acquired of a novel anthropomorphic phantom and a cohort of 12 patients. SynCTs were generated by combining an ultra-short echo time (UTE) sequence with other MRI datasets using voxel-based weighted summation. For the phantom, DRRs from synCT and CT were compared via bounding box and landmark analysis. Planar (MV/KV) and volumetric (CBCT) IGRT performancemore » were evaluated across several platforms. In patients, retrospective analysis was conducted to register CBCTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system using whole brain and local registration techniques. A semi-automatic registration program was developed and validated to rigidly register planar MV/KV images (n=37) to synCT and CT DRRs. Registration reproducibility was assessed and margin differences were characterized using the van Herk formalism. Results: Bounding box and landmark analysis of phantom synCT DRRs were within 1mm of CT DRRs. Absolute 2D/2D registration shift differences ranged from 0.0–0.7mm for phantom DRRs on all treatment platforms and 0.0–0.4mm for volumetric registrations. For patient planar registrations, mean shift differences were 0.4±0.5mm (range: −0.6–1.6mm), 0.0±0.5mm, (range: −0.9–1.2mm), and 0.1±0.3mm (range: −0.7–0.6mm) for the superior-inferior(S-I), left-right(L–R), and anterior-posterior(A-P) axes, respectively. Mean shift differences in volumetric registrations were 0.6±0.4mm (range: −0.2–1.6mm), 0.2±0.4mm (range: −0.3–1.2mm), and 0.2±0.3mm (range: −0.2–1.2mm) for S-I, L–R, and A–P axes, respectively. CT-SIM and synCT derived margins were within 0.3mm

  5. A taxonomic revision of small neotropical saurian Malarias allied to Plasmodium minasense.

    PubMed

    Telford, S R

    1979-01-01

    Saurian malaria species which produce schizonts smaller than normal erythrocyte nuclei, with 4-8 merozoietes and gametocytes equal to or smaller than erythrocyte nuclei in size, parasitizing hosts of the lizard families Scincidae, Iguanidae and Teiidae in the Neotropics are considered to be Plasmodium minasense Carini and Rudolph, 1912. Subspecific designations are given to distinctive populations parasitizing different host species: P. minasense minasense is recognized from the type host, Mabuya mabouya of Brasil; P. minasense carinii Leger and Mouzels, 1917 from Iguana iguana of coastal South America; P. minasense anolisi subsp. nov. from Anolis limifrons of Panama; P. minasense capitoi subsp. nov. from Anolis capito of Panama; P. minasense plicae subsp. nov. from Plica umbra of Guyana; P. minasense tegui subsp. nov. from Tupinambis teguixin of Venezuela; and P. minasense diminutivum Telford, 1973, new combination, from Ameiva ameiva of Panama. Plasmodium rhadinurum Thompson and Huff, 1944 is recognized as a distinct species at present on the basis of possessing schizonts of different shape, asexual stages with filamentous projections in most portions of its range, and larger gametocytes, as well as apparent sympatry with P. minasense carinii in some areas.

  6. Tristetraprolin inhibits mitochondrial function through suppression of α-Synuclein expression in cancer cells

    PubMed Central

    Vo, Mai-Tram; Choi, Seong Hee; Lee, Ji-Heon; Hong, Chung Hwan; Kim, Jong Soo; Lee, Unn Hwa; Chung, Hyung-Min; Lee, Byung Ju; Park, Jeong Woo; Cho, Wha Ja

    2017-01-01

    Mitochondrial dynamics play critical roles in maintaining mitochondrial functions. Here, we report a novel mechanism for regulation of mitochondrial dynamics mediated by tristetraprolin (TTP), an AU-rich element (ARE)-binding protein. Overexpression of TTP resulted in elongated mitochondria, down-regulation of mitochondrial oxidative phosphorylation, reduced membrane potential, cytochrome c release, and increased apoptotic cell death in cancer cells. TTP overexpression inhibited the expression of α-Synuclein (α-Syn). TTP bound to the ARE within the mRNA 3′-untranslated regions (3′-UTRs) of α-Syn and enhanced the decay of α-Syn mRNA. Overexpression of α-Syn without the 3′-UTR restored TTP-induced defects in mitochondrial morphology, mitochondrial oxidative phosphorylation, membrane potential, and apoptotic cell death. Taken together, our data demonstrate that TTP acts as a regulator of mitochondrial dynamics through enhancing degradation of α-Syn mRNA in cancer cells. This finding will increase understanding of the molecular basis of mitochondrial dynamics. PMID:28410208

  7. Dioleoyl-phosphatidic acid selectively binds to α-synuclein and strongly induces its aggregation.

    PubMed

    Mizuno, Satoru; Sasai, Hirotaka; Kume, Aiko; Takahashi, Daisuke; Satoh, Mamoru; Kado, Sayaka; Sakane, Fumio

    2017-03-01

    α-Synuclein (α-syn), which causally links to Parkinson's disease, binds to vesicles containing phosphatidic acid (PA). However, the effects of the fatty acyl chains of PA on its ability to bind to α-syn protein remain unclear. Intriguingly, we reveal that among several PA species, 18:1/18:1-PA is the most strongly bound PA to the α-syn protein. Moreover, 18:1/18:1-PA more strongly enhances secondary structural changes from the random coil form to the α-helical form than 16:0/18:1-PA. Furthermore, 18:1/18:1-PA more markedly accelerates generation of multimeric and proteinase K-resistant α-syn protein compared to 16:0/18:1-PA. These results indicate that among phospholipids examined so far, 18:1/18:1-PA demonstrates the strongest binding to α-syn, as well as the most effective enhancement of its secondary structural changes and aggregation formation. © 2017 Federation of European Biochemical Societies.

  8. DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice.

    PubMed

    Wang, Degui; Yu, Tianyu; Liu, Yongqiang; Yan, Jun; Guo, Yingli; Jing, Yuhong; Yang, Xuguang; Song, Yanfeng; Tian, Yingxia

    2016-12-02

    Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Theoretical Modeling of Molecular and Electron Kinetic Processes. Volume I. Theoretical Formulation of Analysis and Description of Computer Program.

    DTIC Science & Technology

    1979-01-01

    syn- thesis proceed s by ignoring unacceptable syntax or other errors , pro- tection against subsequent execution of a faulty reaction scheme can be...resulting TAPE9 . During subroutine syn thesis and reaction processing, a search is made (fo r each secondary electron collision encountered) to...program library, which can be cat- alogued and saved if any future specialized modifications (beyond the scope of the syn thesis capability of LASER

  10. FTY720/Fingolimod Reduces Synucleinopathy and Improves Gut Motility in A53T Mice

    PubMed Central

    Vidal-Martínez, Guadalupe; Vargas-Medrano, Javier; Gil-Tommee, Carolina; Medina, David; Garza, Nathan T.; Yang, Barbara; Segura-Ulate, Ismael; Dominguez, Samantha J.; Perez, Ruth G.

    2016-01-01

    Patients with Parkinson's disease (PD) often have aggregated α-synuclein (aSyn) in enteric nervous system (ENS) neurons, which may be associated with the development of constipation. This occurs well before the onset of classic PD motor symptoms. We previously found that aging A53T transgenic (Tg) mice closely model PD-like ENS aSyn pathology, making them appropriate for testing potential PD therapies. Here we show that Tg mice overexpressing mutant human aSyn develop ENS pathology by 4 months. We then evaluated the responses of Tg mice and their WT littermates to the Food and Drug Administration-approved drug FTY720 (fingolimod, Gilenya) or vehicle control solution from 5 months of age. Long term oral FTY720 in Tg mice reduced ENS aSyn aggregation and constipation, enhanced gut motility, and increased levels of brain-derived neurotrophic factor (BDNF) but produced no significant change in WT littermates. A role for BDNF was directly assessed in a cohort of young A53T mice given vehicle, FTY720, the Trk-B receptor inhibitor ANA-12, or FTY720 + ANA-12 from 1 to 4 months of age. ANA-12-treated Tg mice developed more gut aSyn aggregation as well as constipation, whereas FTY720-treated Tg mice had reduced aSyn aggregation and less constipation, occurring in part by increasing both pro-BDNF and mature BDNF levels. The data from young and old Tg mice revealed FTY720-associated neuroprotection and reduced aSyn pathology, suggesting that FTY720 may also benefit PD patients and others with synucleinopathy. Another finding was a loss of tyrosine hydroxylase immunoreactivity in gut neurons with aggregated aSyn, comparable with our prior findings in the CNS. PMID:27528608

  11. Elucidating the Role of Site-Specific Nitration of α-Synuclein in the Pathogenesis of Parkinson's Disease via Protein Semisynthesis and Mutagenesis.

    PubMed

    Burai, Ritwik; Ait-Bouziad, Nadine; Chiki, Anass; Lashuel, Hilal A

    2015-04-22

    Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of intraneuronal inclusions consisting of aggregated and post-translationally modified α-synuclein (α-syn). Despite advances in the chemical synthesis of α-syn and other proteins, the generation of site-specifically nitrated synthetic proteins has not been reported. Consequently, it has not been possible to determine the roles of nitration at specific residues in regulating the physiological and pathogenic properties of α-syn. Here we report, for the first time, the site-specific incorporation of 3-nitrotyrosine at different regions of α-syn using native chemical ligation combined with a novel desulfurization strategy. This strategy enabled us to investigate the role of nitration at single or multiple tyrosine residues in regulating α-syn structure, membrane binding, oligomerization, and fibrils formation. We demonstrate that different site-specifically nitrated α-syn species exhibit distinct structural and aggregation properties and exhibit reduced affinity to negatively charged vesicle membranes. We provide evidence that intermolecular interactions between the N- and C-terminal regions of α-syn play critical roles in mediating nitration-induced α-syn oligomerization. For example, when Y39 is not available for nitration (Y39F and Y39/125F), the extent of cross-linking is limited mostly to dimer formation, whereas mutants in which Y39 along with one or multiple C-terminal tyrosines (Y125F, Y133F, Y136F and Y133/136F) can still undergo nitration readily to form higher-order oligomers. Our semisynthetic strategy for generating site-specifically nitrated proteins opens up new possibilities for investigating the role of nitration in regulating protein structure and function in health and disease.

  12. Afrotropical flea beetle genera: a key to their identification, updated catalogue and biogeographical analysis (Coleoptera, Chrysomelidae, Galerucinae, Alticini)

    PubMed Central

    Biondi, Maurizio; D’Alessandro, Paola

    2012-01-01

    Abstract A revision of the Alticini genera from the Afrotropical region is reported. The paper includes the following for the flea beetle fauna occurring in Sub-Saharan Africa and Madagascar: a key to their identification; habitus photos of all the genera; microscope and scanning electron micrographs of many diagnostic morphological characters; and an updated annotated catalogue with biogeographical notes that include new distributional data. The following new synonymies are proposed: Aphthona Chevrolat, 1836 = Ethiopia Scherer, 1972 syn. n.; Sanckia Duvivier, 1891 = Eugonotes Jacoby, 1897 syn. n.; Eurylegna Weise, 1910a = Eurylegniella Scherer, 1972 syn. n.; Kimongona Bechyné, 1959a = Mesocrepis Scherer, 1963 syn. n.; Diphaulacosoma Jacoby, 1892a = Neoderina Bechyné, 1952 syn. n.; Sesquiphaera Bechyné, 1958a = Paropsiderma Bechyné, 1958a syn. n.; Podagrica Chevrolat, 1836 = Podagricina Csiki in Heikertinger and Csiki 1940 syn. n.; Amphimela Chapuis, 1875 = Sphaerophysa Baly, 1876a syn. n. The following new combinations are proposed: Blepharida insignis Brancsik, 1897 = Xanthophysca insignis (Brancsik, 1897) comb. n.; Blepharida multiguttata Duvivier, 1891 = Xanthophysca multiguttata (Duvivier, 1891) comb. n.; Hemipyxis balyana (Csiki in Heikertinger and Csiki 1940) = Pseudadorium balyanum (Csiki in Heikertinger and Csiki, 1940) comb. n.; Hemipyxis brevicornis (Jacoby, 1892a) = Pseudadorium brevicornis (Jacoby, 1892a) comb. n.; Hemipyxis cyanea (Weise, 1910b) = Pseudadorium cyaneum (Weise, 1910b) comb. n.; Hemipyxis gynandromorpha Bechyné, 1958c = Pseudadorium gynandromorphum (Bechyné, 1958c) comb. n.; Hemipyxis latiuscula Bechyné, 1958c = Pseudadorium latiusculum (Bechyné, 1958c) comb. n.; Hemipyxis soror (Weise, 1910b) = Pseudadorium soror (Weise, 1910b) comb. n. The genera Buphonella Jacoby, 1903aand Halticopsis Fairmaire, 1883a are transferred to the tribe Galerucini; the genus Biodontocnema Biondi, 2000 stat. prom. is considered to be valid and

  13. α-Synuclein Aggregated with Tau and β-Amyloid in Human Platelets from Healthy Subjects: Correlation with Physical Exercise

    PubMed Central

    Daniele, Simona; Pietrobono, Deborah; Fusi, Jonathan; Lo Gerfo, Annalisa; Cerri, Eugenio; Chico, Lucia; Iofrida, Caterina; Petrozzi, Lucia; Baldacci, Filippo; Giacomelli, Chiara; Galetta, Fabio; Siciliano, Gabriele; Bonuccelli, Ubaldo; Trincavelli, Maria L.; Franzoni, Ferdinando; Martini, Claudia

    2018-01-01

    The loss of protein homeostasis that has been associated with aging leads to altered levels and conformational instability of proteins, which tend to form toxic aggregates. In particular, brain aging presents characteristic patterns of misfolded oligomers, primarily constituted of β-amyloid (Aβ), tau, and α-synuclein (α-syn), which can accumulate in neuronal membranes or extracellular compartments. Such aging-related proteins can also reach peripheral compartments, thus suggesting the possibility to monitor their accumulation in more accessible fluids. In this respect, we have demonstrated that α-syn forms detectable hetero-aggregates with Aβ or tau in red blood cells (RBCs) of healthy subjects. In particular, α-syn levels and its heteromeric interactions are modulated by plasma antioxidant capability (AOC), which increases in turn with physical activity. In order to understand if a specific distribution of misfolded proteins can occur in other blood cells, a cohort of human subjects was enrolled to establish a correlation among AOC, the level of physical exercise and the concentrations of aging-related proteins in platelets. The healthy subjects were divided depending on their level of physical exercise (i.e., athletes and sedentary subjects) and their age (young and older subjects). Herein, aging-related proteins (i.e., α-syn, tau and Aβ) were confirmed to be present in human platelets. Among such proteins, platelet tau concentration was demonstrated to decrease in athletes, while α-syn and Aβ did not correlate with physical exercise. For the first time, α-syn was shown to directly interact with Aβ and tau in platelets, forming detectable hetero-complexes. Interestingly, α-syn interaction with tau was inversely related to plasma AOC and to the level of physical activity. These results suggested that α-syn heterocomplexes, particularly with tau, could represent novel indicators to monitor aging-related proteins in platelets. PMID:29441013

  14. FTY720/Fingolimod Reduces Synucleinopathy and Improves Gut Motility in A53T Mice: CONTRIBUTIONS OF PRO-BRAIN-DERIVED NEUROTROPHIC FACTOR (PRO-BDNF) AND MATURE BDNF.

    PubMed

    Vidal-Martínez, Guadalupe; Vargas-Medrano, Javier; Gil-Tommee, Carolina; Medina, David; Garza, Nathan T; Yang, Barbara; Segura-Ulate, Ismael; Dominguez, Samantha J; Perez, Ruth G

    2016-09-23

    Patients with Parkinson's disease (PD) often have aggregated α-synuclein (aSyn) in enteric nervous system (ENS) neurons, which may be associated with the development of constipation. This occurs well before the onset of classic PD motor symptoms. We previously found that aging A53T transgenic (Tg) mice closely model PD-like ENS aSyn pathology, making them appropriate for testing potential PD therapies. Here we show that Tg mice overexpressing mutant human aSyn develop ENS pathology by 4 months. We then evaluated the responses of Tg mice and their WT littermates to the Food and Drug Administration-approved drug FTY720 (fingolimod, Gilenya) or vehicle control solution from 5 months of age. Long term oral FTY720 in Tg mice reduced ENS aSyn aggregation and constipation, enhanced gut motility, and increased levels of brain-derived neurotrophic factor (BDNF) but produced no significant change in WT littermates. A role for BDNF was directly assessed in a cohort of young A53T mice given vehicle, FTY720, the Trk-B receptor inhibitor ANA-12, or FTY720 + ANA-12 from 1 to 4 months of age. ANA-12-treated Tg mice developed more gut aSyn aggregation as well as constipation, whereas FTY720-treated Tg mice had reduced aSyn aggregation and less constipation, occurring in part by increasing both pro-BDNF and mature BDNF levels. The data from young and old Tg mice revealed FTY720-associated neuroprotection and reduced aSyn pathology, suggesting that FTY720 may also benefit PD patients and others with synucleinopathy. Another finding was a loss of tyrosine hydroxylase immunoreactivity in gut neurons with aggregated aSyn, comparable with our prior findings in the CNS. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. The type specimens of Tenthredo Linnaeus, 1758 (Hymenoptera: Tenthredinidae) deposited in the Hungarian Natural History Museum.

    PubMed

    Taeger, Andreas

    2013-01-01

    The type specimens of Tenthredo sensu lato deposited in the Hungarian Natural History Museum (Budapest) are reviewed. The following synonyms are recognized and discussed: Rhogogastera aenescens Mocsáry, 1909, syn. nov. of Tenthredo (Temuledo) finschi finschi W.F. Kirby, 1882; Macrophya prasinipes Konow, 1891, syn. nov. of Macrophya caucasica (Mocsáry, 1880); Tenthredo concinnoides Malaise, 1945, syn. nov. of Tenthredo concinna Mocsáry, 1883; Tenthredo fulviventris Mocsáry, 1909, syn. nov. of Tenthredo (Tenthredella) crenata (Enslin, 1912); Tenthredo vespa inaffectata Muche, 1965, syn. nov. of Tenthredo (Tenthredo) vespa Retzius, 1783; Rhogogaster kaszabi Zombori, 1973, syn. nov. of Tenthredo (Eurogaster) aaliensis (Strand, 1898); Tenthredo kaszabi Muche, 1965, syn. nov. of Tenthredo (Eurogaster) mesomela Linné, 1758; Rhogogastera opacella Mocsáry, 1909, syn. nov. of Tenthredo (Eurogaster) stulta Jakowlew, 1891; Tenthredo tschinggischanensis Muche, 1965 syn. nov. of Tenthredo (Tenthredella) balteata Klug, 1817; Tenthredo unfasciata Mocsáry, 1909, syn. nov. of Tenthredo (Tenthredella) colon Klug, 1817; Tenthredella cucullata Enslin, 1912, syn. nov. of Tenthredo (Tenthredella) colon Klug, 1817. Macrophya caucasica (Mocsáry, 1880) is a new combination (comb. nov.) for Allantus caucasicus Mocsáry, 1880. Tenthredo semicolon Mol, is a replacement name (nom. nov.) for Tenthredo punctulata Konow, 1887, nom. praeocc., nec Klug, 1817. Tenthredo chanae Taeger & Shinohara spec. nov., a species close to Tenthredo concinna, is described from Taiwan. Lectotypes are designated and illustrated for the following 30 nominal taxa: Rhogogastera aenescens Mocsáry, 1909; Allantus albiventris Mocsáry, 1880; Allantus almasyanus Mocsáry, 1909; Macrophya binaculata Mocsáry, 1909; Allantus brachycerus Mocsáry, 1909; Allantus caucasicus Mocsáry, 1880; Allantus centrorufus Mocsáry, 1909; Tenthredo chyzeri Mocsáry, 1891; Tenthredo concinna Mocsáry, 1883; Tenthredo concinnoides

  16. Gastrointestinal Parasites of Ecuadorian Mantled Howler Monkeys (Alouatta palliata aequatorialis) Based on Fecal Analysis.

    PubMed

    Helenbrook, William D; Wade, Susan E; Shields, William M; Stehman, Stephen V; Whipps, Christopher M

    2015-06-01

    An analysis of gastrointestinal parasites of Ecuadorian mantled howler monkeys, Alouatta palliata aequatorialis, was conducted based on examination of fecal smears, flotations, and sedimentations. At least 1 type of parasite was detected in 97% of the 96 fecal samples screened across 19 howler monkey groups using these techniques. Samples averaged 3.6 parasite species per individual (±1.4 SD). Parasites included species representing genera of 2 apicomplexans: Cyclospora sp. (18% of individual samples) and Isospora sp. (3%); 6 other protozoa: Balantidium sp. (9%), Blastocystis sp. (60%), Chilomastix sp. (4%), Dientamoeba sp. (3%), Entamoeba species (56%), Iodamoeba sp. (5%); 4 nematodes: Enterobius sp. (3%), Capillaria sp. (78%), Strongyloides spp. (88%) which included 2 morphotypes, Trypanoxyuris sp. (12%); and the platyhelminth Controrchis sp. (15%). A statistically significant positive correlation was found between group size and each of 3 different estimators of parasite species richness adjusted for sampling effort (ICE: r(2) = 0.24, P = 0.05; Chao2: r(2) = 0.25, P = 0.05, and Jackknife: r(2) = 0.31, P = 0.03). Two significant associations between co-infecting parasites were identified. Based on the prevalence data, individuals infected with Balantidium sp. were more likely to also be infected with Isospora sp. (χ(2) = 6.02, P = 0.01), while individuals harboring Chilomastix sp. were less likely to have Capillaria sp. present (χ(2) = 4.03, P = 0.04).

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rycyna, R.E.; Alderfer, J.L.

    Uridylyl(3'-5')uridine (UpU) is subjected to aqueous acetone photosensitized radiation with sunlamps. These irradiation conditions form only cyclobutane-type photodimers. Purification of a specific configurational photodimer is accomplished by using C-18 reverse-phase high-performance liquid chromatography. Multinuclear NMR analysis is used to analyze photoproduct formation and to determine conformational features of these photodimers. Four photodimers are identified, with the cis-syn isomer predominant. The cis-syn and trans-syn photodimers of UpU exhibit markedly different furanose and exocyclic bond conformations. A comparison of the properties of the cis-syn dimers of UpU with those of dTpdT reveal many similar conformational features but also some that are different.

  18. Keys to genera of the spider wasps (Hymenoptera: Pompilidae) of Russia and neighbouring countries, with check-list of genera.

    PubMed

    Loktionov, Valery M; Lelej, Arkady S

    2015-10-28

    Keys to 55 genera of spider wasps of Russia and neighbouring countries in females and males are given. Of them 34 genera are distributed in Russia. An annotated list of genera with type species and distribution data within Russia and biogeographical regions is given. The genus Xenaporus Ashmead, 1902 and X. eremocanus Wolf, 1990 are newly recorded from Russia. According to ICZN 1995 (Opinion 1820) new synonymy (valid name first) is proposed for the type species of genus Cryptocheilus Panzer, 1806: Sphex annulata Fabricius, 1798 (=Pompilus alternatus Lepeletier de Saint Fargeau, 1845, syn. nov.; =Pompilus comparatus Smith, 1855, syn. nov.; =Priocnemis culpabilis Costa, 1893, syn. nov.; Salius annulatilis Richards, 1935, syn. nov.).

  19. Alpha-synuclein is present in dental calculus but not altered in Parkinson's disease patients in comparison to controls.

    PubMed

    Schmid, Sabrina; Goldberg-Bockhorn, Eva; Schwarz, Silke; Rotter, Nicole; Kassubek, Jan; Del Tredici, Kelly; Pinkhardt, Elmar; Otto, Markus; Ludolph, Albert C; Oeckl, Patrick

    2018-06-01

    In autopsy cases staged for sporadic Parkinson's disease (PD), the neuropathology is characterized by a preclinical phase that targets the enteric nervous system of the gastrointestinal tract (GIT). Therefore, the ENS might be a source of potential (presymptomatic) PD biomarkers. In this clinically based study, we examined the alpha-synuclein (αSyn) concentration in an easily accessible protein storage medium of the GIT, dental calculus, in 21/50 patients with PD and 28/50 age- and gender-matched controls using ELISA. αSyn was detectable in dental calculus and the median concentration in the control patients was 8.6 pg/mg calculus (interquartile range 2.6-13.1 pg/mg). αSyn concentrations were significantly influenced by blood contamination and samples with a hemoglobin concentration of > 4000 ng/mL were excluded. There was no significant difference of αSyn concentrations in the dental calculus of PD patients (5.76 pg/mg, interquartile range 2.91-9.74 pg/mg) compared to those in controls (p = 0.40). The total αSyn concentration in dental calculus is not a suitable biomarker for sporadic PD. Disease-related variants such as oligomeric or phosphorylated αSyn in calculus might prove to be more specific.

  20. Site-specific structural dynamics of α-Synuclein revealed by time-resolved fluorescence spectroscopy: a review

    NASA Astrophysics Data System (ADS)

    Sahay, Shruti; Krishnamoorthy, G.; Maji, Samir K.

    2016-12-01

    Aggregation of α-Synuclein (α-Syn) into amyloid fibrils is known to be associated with the pathogenesis of Parkinson’s disease (PD). Several missense mutations of the α-Syn gene have been associated with rare, early onset familial forms of PD. Despite several studies done so far, the local/residue-level structure and dynamics of α-Syn in its soluble and aggregated fibril form and how these are affected by the familial PD associated mutations are still not clearly understood. Here, we review studies performed by our group as well as other research groups, where time-resolved fluorescence spectroscopy has been used to understand the site-specific structure and dynamics of α-Syn under physiological conditions as well as under conditions that alter the aggregation properties of the protein such as low pH, high temperature, presence of membrane mimics and familial PD associated mutations. These studies have provided important insights into the critical structural properties of α-Syn that may govern its aggregation. The review also highlights time-resolved fluorescence as a promising tool to study the critical conformational transitions associated with early oligomerization of α-Syn, which are otherwise not accessible using other commonly used techniques such as thioflavin T (ThT) binding assay.

  1. The lysosomal enzyme alpha-Galactosidase A is deficient in Parkinson's disease brain in association with the pathologic accumulation of alpha-synuclein.

    PubMed

    Nelson, Michael P; Boutin, Michel; Tse, Tonia E; Lu, Hailin; Haley, Emily D; Ouyang, Xiaosen; Zhang, Jianhua; Auray-Blais, Christiane; Shacka, John J

    2018-02-01

    The aberrant accumulation of alpha-synuclein (α-syn) is believed to contribute to the onset and pathogenesis of Parkinson's disease (PD). The autophagy-lysosome pathway (ALP) is responsible for the high capacity clearance of α-syn. ALP dysfunction is documented in PD and pre-clinical evidence suggests that inhibiting the ALP promotes the pathological accumulation of α-syn. We previously identified the pathological accumulation of α-syn in the brains of mice deficient for the soluble lysosomal enzyme alpha-Galactosidase A (α-Gal A), a member of the glycosphingolipid metabolism pathway. In the present study, we quantified α-Gal A activity and levels of its glycosphingolipid metabolites in postmortem temporal cortex specimens from control individuals and in PD individuals staged with respect to α-syn containing Lewy body pathology. In late-state PD temporal cortex we observed significant decreases in α-Gal A activity and the 46kDa "active" species of α-Gal A as determined respectively by fluorometric activity assay and western blot analysis. These decreases in α-Gal A activity/levels correlated significantly with increased α-syn phosphorylated at serine 129 (p129S-α-syn) that was maximal in late-stage PD temporal cortex. Mass spectrometric analysis of 29 different isoforms of globotriaosylceramide (Gb 3 ), a substrate of α-Gal A indicated no significant differences with respect to different stages of PD temporal cortex. However, significant correlations were observed between increased levels of several Gb 3 isoforms and with decreased α-Gal A activity and/or increased p129S-α-syn. Deacylated Gb 3 (globotriaosylsphingosine or lyso-Gb 3 ) was also analyzed in PD brain tissue but was below the limit of detection of 20pmol/g. Analysis of other lysosomal enzymes revealed a significant decrease in activity for the lysosomal aspartic acid protease cathepsin D but not for glucocerebrosidase (GCase) or cathepsin B in late-stage PD temporal cortex. However, a

  2. Renal capillariasis in the small Indian mongoose, Herpestes auropunctatus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huizinga, H.W.; Cosgrove, G.E.; Sturrock, R.F.

    1976-01-01

    A Capillaria sp. was recovered from the kidneys of 28 (93.3 percent) of 30 small Indian mongooses (Herpestes auropunctus) collected in St. Lucia, West Indies. The nematodes were embedded within distended pelvic fornices of the kidney and surrounded by accumulations of eggs. A chronic, low-level inflammation of the transitional epithelium was characterized by hyperplasia, giant cells surrounding embedded eggs and a plasmacytic infiltration. This is the first record of a capillarid nematode from the kidney of the mongoose.

  3. Anle138b Partly Ameliorates Motor Deficits Despite Failure of Neuroprotection in a Model of Advanced Multiple System Atrophy

    PubMed Central

    Fellner, Lisa; Kuzdas-Wood, Daniela; Levin, Johannes; Ryazanov, Sergey; Leonov, Andrei; Griesinger, Christian; Giese, Armin; Wenning, Gregor K.; Stefanova, Nadia

    2016-01-01

    The neurodegenerative disorder multiple system atrophy (MSA) is characterized by autonomic failure, cerebellar ataxia and parkinsonism in any combination associated with predominantly oligodendroglial α-synuclein (α-syn) aggregates (glial cytoplasmic inclusions = GCIs). To date, there is no effective disease modifying therapy. Previous experiments have shown that the aggregation inhibitor anle138b reduces neurodegeneration, as well as behavioral deficits in both transgenic and toxin mouse models of Parkinson's disease (PD). Here we analyzed whether anle138b improves motor skills and reduces neuronal loss, as well as oligodendroglial α-syn aggregation in the PLP-α-syn transgenic mouse challenged with the mitochondrial toxin 3-nitropropionic acid (3-NP) to model full-blown MSA. Following 1 month of treatment with anle138b, MSA mice showed signs of motor improvement affecting stride length, but not pole, grip strength, and beam test performance. Loss of dopaminergic nigral neurons and Purkinje cells was not attenuated and GCI density remained unchanged. These data suggest that the pathology in transgenic PLP-α-syn mice receiving 3-NP might be too advanced to detect significant effects of anle138b treatment on neuronal loss and intracytoplasmic α-syn inclusion bodies. However, the partial motor amelioration may indicate potential efficacy of anle138b treatment that may be mediated by its actions on α-syn oligomers or may reflect improvement of neuronal dysfunction in neural at risk populations. Further studies are required to address the efficacy of anle138b in transgenic α-syn models of early-stage MSA and in the absence of additional toxin application. PMID:27013960

  4. Ethylene Regulates the Physiology of the Cyanobacterium Synechocystis sp. PCC 6803 via an Ethylene Receptor.

    PubMed

    Lacey, Randy F; Binder, Brad M

    2016-08-01

    Ethylene is a plant hormone that plays a crucial role in the growth and development of plants. The ethylene receptors in plants are well studied, and it is generally assumed that they are found only in plants. In a search of sequenced genomes, we found that many bacterial species contain putative ethylene receptors. Plants acquired many proteins from cyanobacteria as a result of the endosymbiotic event that led to chloroplasts. We provide data that the cyanobacterium Synechocystis (Synechocystis sp. PCC 6803) has a functional receptor for ethylene, Synechocystis Ethylene Response1 (SynEtr1). We first show that SynEtr1 directly binds ethylene. Second, we demonstrate that application of ethylene to Synechocystis cells or disruption of the SynEtr1 gene affects several processes, including phototaxis, type IV pilus biosynthesis, photosystem II levels, biofilm formation, and spontaneous cell sedimentation. Our data suggest a model where SynEtr1 inhibits downstream signaling and ethylene inhibits SynEtr1. This is similar to the inverse-agonist model of ethylene receptor signaling proposed for plants and suggests a conservation of structure and function that possibly originated over 1 billion years ago. Prior research showed that SynEtr1 also contains a light-responsive phytochrome-like domain. Thus, SynEtr1 is a bifunctional receptor that mediates responses to both light and ethylene. To our knowledge, this is the first demonstration of a functional ethylene receptor in a nonplant species and suggests that that the perception of ethylene is more widespread than previously thought. © 2016 American Society of Plant Biologists. All Rights Reserved.

  5. Ethylene Regulates the Physiology of the Cyanobacterium Synechocystis sp. PCC 6803 via an Ethylene Receptor1[OPEN

    PubMed Central

    2016-01-01

    Ethylene is a plant hormone that plays a crucial role in the growth and development of plants. The ethylene receptors in plants are well studied, and it is generally assumed that they are found only in plants. In a search of sequenced genomes, we found that many bacterial species contain putative ethylene receptors. Plants acquired many proteins from cyanobacteria as a result of the endosymbiotic event that led to chloroplasts. We provide data that the cyanobacterium Synechocystis (Synechocystis sp. PCC 6803) has a functional receptor for ethylene, Synechocystis Ethylene Response1 (SynEtr1). We first show that SynEtr1 directly binds ethylene. Second, we demonstrate that application of ethylene to Synechocystis cells or disruption of the SynEtr1 gene affects several processes, including phototaxis, type IV pilus biosynthesis, photosystem II levels, biofilm formation, and spontaneous cell sedimentation. Our data suggest a model where SynEtr1 inhibits downstream signaling and ethylene inhibits SynEtr1. This is similar to the inverse-agonist model of ethylene receptor signaling proposed for plants and suggests a conservation of structure and function that possibly originated over 1 billion years ago. Prior research showed that SynEtr1 also contains a light-responsive phytochrome-like domain. Thus, SynEtr1 is a bifunctional receptor that mediates responses to both light and ethylene. To our knowledge, this is the first demonstration of a functional ethylene receptor in a nonplant species and suggests that that the perception of ethylene is more widespread than previously thought. PMID:27246094

  6. Rifting and Subsidence in the Gulf of Mexico: Implications for Syn-rift, Sag, and Salt Sections, and Subsequent Paleogeography

    NASA Astrophysics Data System (ADS)

    Pindell, J. L.; Graham, R.; Horn, B.

    2013-05-01

    Thick (up to 5 km), rapid (<3 Ma), salt deposition is problematic for basin modelling because such accommodation cannot be thermal, yet GoM salt deposits (Late Callovian-Early Oxfordian) appear to be post-rift (most salt overlies planar sub-salt unconformities on syn-rift section). One possible solution is that the pre-drift GoM was a deep (~2 km) air-filled rift depression where basement had already subsided tectonically, and thus could receive up to 5 km of salt, roughly the isostatic maximum on exhumed mantle, hyper-thinned continent, or new ocean crust. ION-GXT and other seismic data along W Florida and NW Yucatán show that (1) mother salt was only 1 km thick in these areas, (2) that these areas were depositionally connected to areas of thicker deposition, and (3) the top of all salt was at global sea level, and hence the sub-salt unconformity along Florida and Yucatán was only 1 km deep by end of salt deposition. These observations fit the air-filled chasm hypothesis; however, two further observations make that mechanism highly improbable: (1) basinward limits of sub-salt unconformities along Florida/Yucatán are deeper than top of adjacent ocean crust emplaced at ~2.7 km subsea (shown by backstripping), and (2) deepest abyssal sediments over ocean crust onlap the top of distal salt, demonstrating that the salt itself was rapidly drowned after deposition. Study of global ION datasets demonstrates the process of "rapid outer marginal collapse" at most margins, which we believe is achieved by low-angle detachment on deep, landward-dipping, Moho-equivalent surfaces such that outer rifted margins are hanging walls of crustal scale half-grabens over mantle. The tectonic accommodation space produced (up to 3 km, < 3 Ma) can be filled by ~5 km of sag/salt sequences with little apparent hanging wall rifting. When salt (or other) deposition lags behind, or ends during, outer marginal collapse, deep-water settings result. We suggest that this newly identified, "outer

  7. NMR structural studies of the ionizing radiation adduct 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) opposite deoxyadenosine in a DNA duplex. 8-oxo-7H-dG(syn)ter dot dA(anti) alignment at lesion site

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kouchakdjian, M.; Patel, D.J.; Bodepudi, V.

    1991-02-05

    Proton NMR studies are reported on the complementary d(C1-C2-A3-C4-T5-A6-oxo-G7-T8-C9-A10-C11-C12){center dot}d(G13-G14-T15-G16-A17-A18-T19-A20-G21-T22-G23-G24) dodecanucleotide duplex (designated 8-oxo-7H-dG{center dot}dA 12-mer), which contains a centrally located 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) residue, a group commonly found in DNA that has been exposed to ionizing radiation or oxidizing free radicals. From the NMR spectra it can be deduced that this moiety exists as two tautomers, or gives rise to two DNA conformations, that are in equilibrium and that exchange slowly. The present study focuses on the major component of the equilibrium that originates in the 6,8-dioxo tautomer of 8-oxo-7H-dG. The authors have assigned the exchangeable NH1, NH7, and NH{submore » 2}-2 base protons located on the Watson-Crick and Hoogsteen edges of 8-oxo-7H-dG7 in the 8-oxo-7H-dG{center dot}dA 12-mer duplex, using an analysis of one- and two-dimensional nuclear Overhauser enhancement (NOE) data in H{sub 2}O solution. They were able to detect a set of intra- and interstrand NOEs between protons (exchangeable and nonexchangeable) on adjacent residues in the d(A6-oxo-G7-T8){center dot}d(A17-A18-T19) trinucleotide segment centered about the lesion site that establishes stacking of the oxo-dG7(syn){center dot}dA(anti) pair between stable Watson-Crick dA6{center dot}dT19 and dT8{center dot}A17 base pairs with minimal perturbation of the helix. The structural studies demonstrate that 8-oxo-7H-dG(syn){center dot}dA(anti) forms a stable pair in the interior of the helix, providing a basis for the observed incorporation of dA opposite 8-oxo-7H-dG when readthrough occurs past this oxidized nucleoside base.« less

  8. Image Guided Radiation Therapy Using Synthetic Computed Tomography Images in Brain Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Price, Ryan G.; Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan; Kim, Joshua P.

    Purpose: The development of synthetic computed tomography (CT) (synCT) derived from magnetic resonance (MR) images supports MR-only treatment planning. We evaluated the accuracy of synCT and synCT-generated digitally reconstructed radiographs (DRRs) relative to CT and determined their performance for image guided radiation therapy (IGRT). Methods and Materials: Magnetic resonance simulation (MR-SIM) and CT simulation (CT-SIM) images were acquired of an anthropomorphic skull phantom and 12 patient brain cancer cases. SynCTs were generated using fluid attenuation inversion recovery, ultrashort echo time, and Dixon data sets through a voxel-based weighted summation of 5 tissue classifications. The DRRs were generated from the phantommore » synCT, and geometric fidelity was assessed relative to CT-generated DRRs through bounding box and landmark analysis. An offline retrospective analysis was conducted to register cone beam CTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system. Planar MV and KV images (n=37) were rigidly registered to synCT and CT DRRs using an in-house script. Planar and volumetric registration reproducibility was assessed and margin differences were characterized by the van Herk formalism. Results: Bounding box and landmark analysis of phantom synCT DRRs were within 1 mm of CT DRRs. Absolute planar registration shift differences ranged from 0.0 to 0.7 mm for phantom DRRs on all treatment platforms and from 0.0 to 0.4 mm for volumetric registrations. For patient planar registrations, the mean shift differences were 0.4 ± 0.5 mm (range, −0.6 to 1.6 mm), 0.0 ± 0.5 mm (range, −0.9 to 1.2 mm), and 0.1 ± 0.3 mm (range, −0.7 to 0.6 mm) for the superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) axes, respectively. The mean shift differences in volumetric registrations were 0.6 ± 0.4 mm (range, −0.2 to 1.6 mm), 0.2 ± 0.4 mm (range, −0.3 to 1.2 mm), and 0.2

  9. Matrix photochemical study and conformational analysis of CH3C(O)NCS and CF3C(O)NCS.

    PubMed

    Ramos, Luis A; Ulic, Sonia E; Romano, Rosana M; Beckers, Helmut; Willner, Helge; Della Védova, Carlos O

    2014-01-30

    The vapor of acetyl isocyanide, CH3C(O)NCS, and trifluoroacetyl isocyanide, CF3C(O)NCS, were isolated in solid Ar at 15 K. The existence of rotational isomerism was confirmed when the matrixes were irradiated with broad-band UV-vis light (200 ≤ λ ≤ 800 nm) and also by temperature-dependent Ar-matrix IR spectroscopy. The initial spectra showed the vapor of CH3C(O)NCS and CF3C(O)NCS consist of two conformers syn-syn and syn-anti (with the C═O bond syn with respect to the C-H or C-F bond and syn or anti with respect to the N═C double bond). When CH3C(O)NCS is irradiated, simultaneously with the randomization process, H2CCO and HSCN are produced. In the case of the photolysis of CF3C(O)NCS, the main products are CF3NCS and CO. The assignment of the IR bands to the different photoproducts was made on the basis of the usual criteria, taking account reported antecedents in the literature.

  10. Basic science breaks through: New therapeutic advances in Parkinson's disease.

    PubMed

    Brundin, Patrik; Atkin, Graham; Lamberts, Jennifer T

    2015-09-15

    Parkinson's disease (PD) is the second most common neurodegenerative disease and is typically associated with progressive motor dysfunction, although PD patients also exhibit a variety of non-motor symptoms. The neuropathological hallmark of PD is intraneuronal inclusions containing primarily α-Synuclein (α-Syn), and several lines of evidence point to α-Syn as a key contributor to disease progression. Thus, basic research in the field of PD is largely focused on understanding the pathogenic properties of α-Syn. Over the past 2 y, these studies helped to identify several novel therapeutic strategies that have the potential to slow PD progression; such strategies include sequestration of extracellular α-Syn through immunotherapy, reduction of α-Syn multimerization or intracellular toxicity, and attenuation of the neuroinflammatory response. This review describes these and other putative therapeutic strategies, together with the basic science research that led to their identification. The current breadth of novel targets for the treatment of PD warrants cautious optimism in the fight against this devastating disease. © 2015 International Parkinson and Movement Disorder Society.

  11. ESCRT-mediated Uptake and Degradation of Brain-targeted α-synuclein Single Chain Antibody Attenuates Neuronal Degeneration In Vivo

    PubMed Central

    Spencer, Brian; Emadi, Sharareh; Desplats, Paula; Eleuteri, Simona; Michael, Sarah; Kosberg, Kori; Shen, Jay; Rockenstein, Edward; Patrick, Christina; Adame, Anthony; Gonzalez, Tania; Sierks, Michael; Masliah, Eliezer

    2014-01-01

    Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species of α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed by Fc receptors. For this study, we investigated an scFV directed against oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B (apoB). The modified scFV showed enhanced brain penetration and was imported into neuronal cells through the endosomal sorting complex required for transport (ESCRT) pathway, leading to lysosomal degradation of α-syn aggregates. Further analysis showed that the scFV was effective at ameliorating neurodegenerative pathology and behavioral deficits observed in the mouse model of dementia with Lewy bodies/Parkinson's disease. Thus, the apoB modification had the effect of both increasing accumulation of the scFV in the brain and directing scFV/α-syn complexes for degradation through the ESCRT pathway, leading to improved therapeutic potential of immunotherapy. PMID:25008355

  12. ESCRT-mediated uptake and degradation of brain-targeted α-synuclein single chain antibody attenuates neuronal degeneration in vivo.

    PubMed

    Spencer, Brian; Emadi, Sharareh; Desplats, Paula; Eleuteri, Simona; Michael, Sarah; Kosberg, Kori; Shen, Jay; Rockenstein, Edward; Patrick, Christina; Adame, Anthony; Gonzalez, Tania; Sierks, Michael; Masliah, Eliezer

    2014-10-01

    Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species of α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed by Fc receptors. For this study, we investigated an scFV directed against oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B (apoB). The modified scFV showed enhanced brain penetration and was imported into neuronal cells through the endosomal sorting complex required for transport (ESCRT) pathway, leading to lysosomal degradation of α-syn aggregates. Further analysis showed that the scFV was effective at ameliorating neurodegenerative pathology and behavioral deficits observed in the mouse model of dementia with Lewy bodies/Parkinson's disease. Thus, the apoB modification had the effect of both increasing accumulation of the scFV in the brain and directing scFV/α-syn complexes for degradation through the ESCRT pathway, leading to improved therapeutic potential of immunotherapy.

  13. Transcriptional profiling of striatal neurons in response to single or concurrent activation of dopamine D2, adenosine A(2A) and metabotropic glutamate type 5 receptors: focus on beta-synuclein expression.

    PubMed

    Canela, Laia; Selga, Elisabet; García-Martínez, Juan Manuel; Amaral, Olavo B; Fernández-Dueñas, Víctor; Alberch, Jordi; Canela, Enric I; Franco, Rafael; Noé, Véronique; Lluís, Carme; Ciudad, Carlos J; Ciruela, Francisco

    2012-10-25

    G protein-coupled receptor oligomerization is a concept which is changing the understanding of classical pharmacology. Both, oligomerization and functional interaction between adenosine A(2A,) dopamine D(2) and metabotropic glutamate type 5 receptors have been demonstrated in the striatum. However, the transcriptional consequences of receptors co-activation are still unexplored. We aim here to determine the changes in gene expression of striatal primary cultured neurons upon isolated or simultaneous receptor activation. Interestingly, we found that 95 genes of the total analyzed (15,866 transcripts and variants) changed their expression in response to simultaneous stimulation of all three receptors. Among these genes, we focused on the β-synuclein (β-Syn) gene (SCNB). Quantitative PCR verified the magnitude and direction of change in expression of SCNB. Since β-Syn belongs to the homologous synuclein family and may be considered a natural regulator of α-synuclein (α-Syn), it has been proposed that β-Syn might act protectively against α-Syn neuropathology. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Recapitulating the Structural Evolution of Redox Regulation in Adenosine 5'-Phosphosulfate Kinase from Cyanobacteria to Plants.

    PubMed

    Herrmann, Jonathan; Nathin, David; Lee, Soon Goo; Sun, Tony; Jez, Joseph M

    2015-10-09

    In plants, adenosine 5'-phosphosulfate (APS) kinase (APSK) is required for reproductive viability and the production of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfur donor in specialized metabolism. Previous studies of the APSK from Arabidopsis thaliana (AtAPSK) identified a regulatory disulfide bond formed between the N-terminal domain (NTD) and a cysteine on the core scaffold. This thiol switch is unique to mosses, gymnosperms, and angiosperms. To understand the structural evolution of redox control of APSK, we investigated the redox-insensitive APSK from the cyanobacterium Synechocystis sp. PCC 6803 (SynAPSK). Crystallographic analysis of SynAPSK in complex with either APS and a non-hydrolyzable ATP analog or APS and sulfate revealed the overall structure of the enzyme, which lacks the NTD found in homologs from mosses and plants. A series of engineered SynAPSK variants reconstructed the structural evolution of the plant APSK. Biochemical analyses of SynAPSK, SynAPSK H23C mutant, SynAPSK fused to the AtAPSK NTD, and the fusion protein with the H23C mutation showed that the addition of the NTD and cysteines recapitulated thiol-based regulation. These results reveal the molecular basis for structural changes leading to the evolution of redox control of APSK in the green lineage from cyanobacteria to plants. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Conversion of Natively Unstructured α-Synuclein to Its α-Helical Conformation Significantly Attenuates Production of Reactive Oxygen Species

    PubMed Central

    Zhou, Binbin; Hao, Yuanqiang; Wang, Chengshan; Li, Ding; Liu, You-Nian; Zhou, Feimeng

    2012-01-01

    The intracellular α-synuclein (α-syn) protein, whose conformational change and aggregation have been closely linked to the pathology of Parkingson’s disease (PD), is highly populated at the presynaptic termini and remains there in the α-helical conformation. In this study, circular dichroism confirmed that natively unstructured α-syn in aqueous solution was transformed to its α-helical conformation upon addition of trifluoroethanol (TFE). Electrochemical and UV–visible spectroscopic experiments reveal that both Cu(I) and Cu(II) are stabilized, with the former being stabilized by about two orders of magnitude. Compared to unstructured α-syn (Binolfi et al., J. Am. Chem. Soc. 133 (2011) 194–196), α-helical α-syn stabilizes Cu(I) by more than three orders of magnitude. Through the measurements of H2O2 and hydroxyl radicals (OH•) in solutions containing different forms of Cu(II) (free and complexed by unstructured or α-helical α-syn), we demonstrate that the significantly enhanced Cu(I) binding affinity helps inhibit the production of highly toxic reactive oxygen species, especially the hydroxyl radicals. Our study provides strong evidence that, as a possible means to prevent neuronal cell damage, conversion of the natively unstructured α-syn to its α-helical conformation in vivo could significantly attenuate the copper-modulated ROS production. PMID:23123341

  16. Aggregates assembled from overexpression of wild-type alpha-synuclein are not toxic to human neuronal cells.

    PubMed

    Ko, Li-Wen; Ko, Hwai-Hwa C; Lin, Wen-Lang; Kulathingal, Jayanranyan G; Yen, Shu-Hui C

    2008-11-01

    Filamentous alpha-synuclein (alpha-syn) aggregates form Lewy bodies (LBs), the neuropathologic hallmarks of Parkinson disease and related alpha-synucleinopathies. To model Lewy body-associated neurodegeneration, we generated transfectant 3D5 of human neuronal-type in which expression of human wild-type alpha-syn is regulated by the tetracycline off (TetOff)-inducible mechanism. Retinoic acid-elicited differentiation promoted assembly of alpha-syn aggregates after TetOff induction in 3D5 cells. The aggregates accumulated 14 days after TetOff induction were primarily soluble and showed augmented thioflavin affinity with concomitant phosphorylation and nitration of alpha-syn. Extension of the induction led to the formation of sarkosyl-insoluble aggregates that appeared concurrently with thioflavin-positive inclusions. Immunoelectron microscopy revealed that the inclusions consist of dense bundles of 8- to 12-nm alpha-syn fibrils that congregate in the perikarya and resemble Lewy bodies. Most importantly, accumulation of soluble and insoluble aggregates after TetOff induction for 14 and 28 days was reversible and did not compromise the viability of the cells or their subsequent survival. Thus, this chemically defined culture paradigm provides a useful means to elucidate how oxidative injuries and other insults that are associated with aging promote alpha-syn to self-assemble or interact with other molecules leading to neuronal degeneration in alpha-synucleinopathies.

  17. (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis.

    PubMed

    Macedo, Diana; Jardim, Carolina; Figueira, Inês; Almeida, A Filipa; McDougall, Gordon J; Stewart, Derek; Yuste, Jose E; Tomás-Barberán, Francisco A; Tenreiro, Sandra; Outeiro, Tiago F; Santos, Cláudia N

    2018-05-03

    Parkinson's disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action. This constitutes a challenge for the development of (poly)phenol-based nutritional therapies. Here, we subjected (poly)phenols from Arbutus unedo to in vitro digestion and tested the products in cell models of PD based on the cytotoxicity of aSyn. The (poly)phenol-digested metabolites from A. unedo leaves (LPDMs) effectively counteracted aSyn and H 2 O 2 toxicity in yeast and human cells, improving viability by reducing aSyn aggregation and inducing its clearance. In addition, LPDMs modulated pathways associated with aSyn toxicity, such as oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial impairment, and SIR2 expression. Overall, LPDMs reduced aSyn toxicity, enhanced the efficiency of ER-associated protein degradation by the proteasome and autophagy, and reduced oxidative stress. In total, our study opens novel avenues for the exploitation of (poly)phenols in nutrition and health.

  18. Synfograms: a new generation of holographic applications

    NASA Astrophysics Data System (ADS)

    Meulien Öhlmann, Odile; Öhlmann, Dietmar; Zacharovas, Stanislovas J.

    2008-04-01

    The new synthetic Four-dimensional printing technique (Syn4D) Synfogram is introducing time (animation) into spatial configuration of the imprinted three-dimensional shapes. While lenticular solutions offer 2 to 9 stereoscopic images Syn4D offers large format, full colors true 3D visualization printing of 300 to 2500 frames imprinted as holographic dots. This past 2 years Syn4D high-resolution displays proved to be extremely efficient for museums presentation, engineering design, automobile prototyping, and advertising virtual presentation as well as, for portrait and fashion applications. The main advantages of syn4D is that it offers a very easy way of using a variety of digital media, like most of 3D Modelling programs, 3D scan system, video sequences, digital photography, tomography as well as the Syn4D camera track system for life recording of spatial scenes changing in time. The use of digital holographic printer in conjunction with Syn4D image acquiring and processing devices separates printing and imaging creation in such a way that makes four-dimensional printing similar to a conventional digital photography processes where imaging and printing are usually separated in space and time. Besides making content easy to prepare, Syn4D has also developed new display and lighting solutions for trade show, museum, POP, merchandising, etc. The introduction of Synfograms is opening new applications for real life and virtual 4D displays. In this paper we will analyse the 3D market, the properties of the Synfograms and specific applications, the problems we encounter, solutions we find, discuss about customers demand and need for new product development.

  19. Hand-rim forces and gross mechanical efficiency in asynchronous and synchronous wheelchair propulsion: a comparison.

    PubMed

    Lenton, J P; van der Woude, L; Fowler, N; Nicholson, G; Tolfrey, K; Goosey-Tolfrey, V

    2014-03-01

    To compare the force application characteristics at various push frequencies of asynchronous (ASY) and synchronous (SYN) hand-rim propulsion, 8 able-bodied participants performed a separate sub-maximal exercise test on a wheelchair roller ergometer for each propulsion mode. Each test consisted of a series of 5, 4-min exercise blocks at 1.8 m · s-1 - initially at their freely chosen frequency (FCF), followed by four counter-balanced trials at 60, 80, 120 and 140% FCF. Kinetic data was obtained using a SMARTWheel, measuring forces and moments. The gross efficiency (GE) was determined as the ratio of external work done and the total energy expended. The ASY propulsion produced higher force measures for FRES, FTAN, rate of force development & FEF (P<0.05), while there was no difference in GE values (P=0.518). In pair-matched push frequencies (ASY80:SYN60, ASY100:SYN80, ASY120:SYN100 and ASY140:SYN120), ASY propulsion forces remained significantly higher (FRES, FTAN, rate of force development & FEF P<0.05), and there was no significant effect on GE (P=0.456). Both ASY and SYN propulsion demonstrate similar trends: changes in push frequency are accompanied by changes in absolute force even without changes in the gross pattern/trend of force application, FEF or GE. Matched push frequencies continue to produce significant differences in force measures but not GE. This suggests ASY propulsion is the predominant factor in force application differences. The ASY would appear to offer a kinetic disadvantage to SYN propulsion and no physiological advantage under current testing conditions. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Decreased expression of serum- and glucocorticoid-inducible kinase 1 (SGK1) promotes alpha-synuclein increase related with down-regulation of dopaminergic cell in the Substantia Nigra of chronic MPTP-induced Parkinsonism mice and in SH-SY5Y cells.

    PubMed

    Yeo, Sujung; Sung, Backil; Hong, Yeon-Mi; van den Noort, Maurits; Bosch, Peggy; Lee, Sook-Hyun; Song, Jongbeom; Park, Sang-Kyun; Lim, Sabina

    2018-06-30

    Parkinson's disease (PD) is a chronically progressive neurodegenerative disease, with its main pathological hallmarks being a dramatic loss of dopaminergic neurons predominantly in the Substantia Nigra (SN), and the formations of intracytoplasmic Lewy bodies and dystrophic neurites. Alpha-synuclein (α-syn), widely recognized as the most prominent element of the Lewy body, is one of the representative hallmarks in PD. However, the mechanisms behind the increased α-syn expression and aggregation have not yet been clarified. To examine what causes α-syn expression to increase, we analyzed the pattern of gene expression in the SN of mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), where down-regulation of dopaminergic cells occurred. We identified serum- and glucocorticoid-dependent kinase 1 (SGK1) as one of the genes that is evidently downregulated in chronic MPTP-intoxication. The results of Western blot analyses showed that, together with the down-regulation of dopaminergic cells, the decrease in SGK1 expression increased α-syn expression in the SN in a chronic MPTP-induced Parkinsonism mouse. For an examination of the expression correlation between SGK1 and α-syn, SH-5YSY cells were knocked down with SGK1 siRNA then, the downregulation of dopaminergic cells and the increase in the expression of α-syn were observed. These results suggest that decreased expression of SGK1 may play a critical role in increasing the expression of α-syn, which is related with dopaminergic cell death in the SN of chronic MPTP-induced Parkinsonism mice and in SH-SY5Y cells. Copyright © 2018. Published by Elsevier B.V.

  1. Loss or Mislocalization of Aquaporin-4 Affects Diffusion Properties and Intermediary Metabolism in Gray Matter of Mice.

    PubMed

    Pavlin, T; Nagelhus, E A; Brekken, C; Eyjolfsson, E M; Thoren, A; Haraldseth, O; Sonnewald, U; Ottersen, O P; Håberg, A K

    2017-01-01

    The first aim of this study was to determine how complete or perivascular loss of aquaporin-4 (AQP4) water channels affects membrane permeability for water in the mouse brain grey matter in the steady state. Time-dependent diffusion magnetic resonance imaging was performed on global Aqp4 knock out (KO) and α-syntrophin (α-syn) KO mice, in the latter perivascular AQP4 are mislocalized, but still functioning. Control animals were corresponding wild type (WT) mice. By combining in vivo diffusion measurements with the effective medium theory and previously measured extra-cellular volume fractions, the effects of membrane permeability and extracellular volume fraction were uncoupled for Aqp4 and α-syn KO. The second aim was to assess the effect of α-syn KO on cortical intermediary metabolism combining in vivo [1- 13 C]glucose and [1,2- 13 C]acetate injection with ex vivo 13 C MR spectroscopy. Aqp4 KO increased the effective diffusion coefficient at long diffusion times by 5%, and a 14% decrease in membrane water permeability was estimated for Aqp4 KO compared with WT mice. α-syn KO did not affect the measured diffusion parameters. In the metabolic analyses, significantly lower amounts of [4- 13 C]glutamate and [4- 13 C]glutamine, and percent enrichment in [4- 13 C]glutamate were detected in the α-syn KO mice. [1,2- 13 C]acetate metabolism was unaffected in α-syn KO, but the contribution of astrocyte derived metabolites to GABA synthesis was significantly increased. Taken together, α-syn KO mice appeared to have decreased neuronal glucose metabolism, partly compensated for by utilization of astrocyte derived metabolites.

  2. Neural control of blood flow during exercise in human metabolic syndrome.

    PubMed

    Limberg, Jacqueline K; Morgan, Barbara J; Sebranek, Joshua J; Proctor, Lester T; Eldridge, Marlowe W; Schrage, William G

    2014-09-01

    α-Adrenergic-mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome (MetSyn) when compared with control animals. In an attempt to translate such findings to humans, we hypothesized that adults with MetSyn (n = 14, 35 ± 3 years old) would exhibit greater α-adrenergic responsiveness during exercise when compared with age-matched healthy control subjects (n = 16, 31 ± 3 years old). We measured muscle sympathetic nerve activity (MSNA; microneurography) and forearm blood flow (Doppler ultrasound) during dynamic forearm exercise (15% of maximal voluntary contraction). α-Adrenergic agonists (phenylephrine and clonidine) and an antagonist (phentolamine) were infused intra-arterially to assess α-adrenergic receptor responsiveness and restraint, respectively. Resting MSNA was ∼35% higher in adults with MetSyn (P < 0.05), but did not change in either group with dynamic exercise. Clonidine-mediated vasoconstriction was greater in adults with MetSyn (P < 0.01). Group differences in vascular responses to phenylephrine and phentolamine were not detected (P > 0.05). Interestingly, exercise-mediated vasodilatation was greater in MetSyn (P < 0.05). Adults with MetSyn exhibit greater resting MSNA and clonidine-mediated vasoconstriction, yet preserved functional sympatholysis and higher exercise blood flow during low-intensity hand-grip exercise when compared with age-matched healthy control subjects. These results suggest that adults with MetSyn exhibit compensatory vascular control mechanisms capable of preserving blood flow responses to exercise in the face of augmented sympathetic adrenergic activity. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  3. Properties of Streptococcus mutans Grown in a Synthetic Medium: Binding of Glucosyltransferase and In Vitro Adherence, and Binding of Dextran/Glucan and Glycoprotein and Agglutination

    PubMed Central

    Wu-Yuan, Christine D.; Tai, Stella; Slade, Hutton D.

    1979-01-01

    The influence of culture media on various properties of Streptococcus mutans was investigated. Strains of S. mutans (serotypes c, d, f, and g) were grown in a complex medium (Todd-Hewitt broth [THB]) or a synthetic medium (SYN). The SYN cells, in contrast to THB cells, did not bind extracellular glucosyltransferase and did not produce in vitro adherence. Both types of cells possessed constitutive levels of glucosyltransferase. B13 cells grown in SYN plus invertase-treated glucose possessed the same level of constitutive enzyme as THB cells. In contrast to THB cells, the SYN cells of seven serotype strains did not agglutinate upon the addition of high-molecular-weight dextran/glucan. Significant quantities of lower-molecular-weight (2 × 104 or 7 × 104) dextran and B13 glucan were bound by SYN cells. SYN cells agglutinated weakly in anti-glucan serum (titers, 0 to 16), whereas THB cells possessed titers of 32 to 256. Evidence for the existence of a second binding site in agglutination which does not possess a glucan-like polymer has been obtained. B13 cells grown in invertase-treated THB agglutinated to the same degree as normal THB cells. The nature of this site is unknown. SYN cells possess the type-specific polysaccharide antigen. B13 cells did not bind from THB a glycoprotein which reacts with antisera to the A, B, or T blood group antigens or which allows agglutination upon the addition of dextran. The results demonstrate that S. mutans grown in a chemically defined medium possesse markedly different biochemical and biological activities than cells grown in a complex organic medium. PMID:457252

  4. Structure and properties of a complex of α-synuclein and a single-domain camelid antibody.

    PubMed

    De Genst, Erwin J; Guilliams, Tim; Wellens, Joke; O'Day, Elizabeth M; Waudby, Christopher A; Meehan, Sarah; Dumoulin, Mireille; Hsu, Shang-Te Danny; Cremades, Nunilo; Verschueren, Koen H G; Pardon, Els; Wyns, Lode; Steyaert, Jan; Christodoulou, John; Dobson, Christopher M

    2010-09-17

    The aggregation of the intrinsically disordered protein α-synuclein to form fibrillar amyloid structures is intimately associated with a variety of neurological disorders, most notably Parkinson's disease. The molecular mechanism of α-synuclein aggregation and toxicity is not yet understood in any detail, not least because of the paucity of structural probes through which to study the behavior of such a disordered system. Here, we describe an investigation involving a single-domain camelid antibody, NbSyn2, selected by phage display techniques to bind to α-synuclein, including the exploration of its effects on the in vitro aggregation of the protein under a variety of conditions. We show using isothermal calorimetric methods that NbSyn2 binds specifically to monomeric α-synuclein with nanomolar affinity and by means of NMR spectroscopy that it interacts with the four C-terminal residues of the protein. This latter finding is confirmed by the determination of a crystal structure of NbSyn2 bound to a peptide encompassing the nine C-terminal residues of α-synuclein. The NbSyn2:α-synuclein interaction is mediated mainly by side-chain interactions while water molecules cross-link the main-chain atoms of α-synuclein to atoms of NbSyn2, a feature we believe could be important in intrinsically disordered protein interactions more generally. The aggregation behavior of α-synuclein at physiological pH, including the morphology of the resulting fibrillar structures, is remarkably unaffected by the presence of NbSyn2 and indeed we show that NbSyn2 binds strongly to the aggregated as well as to the soluble forms of α-synuclein. These results give strong support to the conjecture that the C-terminal region of the protein is not directly involved in the mechanism of aggregation and suggest that binding of NbSyn2 could be a useful probe for the identification of α-synuclein aggregation in vitro and possibly in vivo. Copyright © 2010. Published by Elsevier Ltd.

  5. Conformational Equilibria in Monomeric α-Synuclein at the Single-Molecule Level

    PubMed Central

    Tessari, Isabella; Mammi, Stefano; Bergantino, Elisabetta; Musiani, Francesco; Brucale, Marco; Bubacco, Luigi; Samorì, Bruno

    2008-01-01

    Human α-Synuclein (αSyn) is a natively unfolded protein whose aggregation into amyloid fibrils is involved in the pathology of Parkinson disease. A full comprehension of the structure and dynamics of early intermediates leading to the aggregated states is an unsolved problem of essential importance to researchers attempting to decipher the molecular mechanisms of αSyn aggregation and formation of fibrils. Traditional bulk techniques used so far to solve this problem point to a direct correlation between αSyn's unique conformational properties and its propensity to aggregate, but these techniques can only provide ensemble-averaged information for monomers and oligomers alike. They therefore cannot characterize the full complexity of the conformational equilibria that trigger the aggregation process. We applied atomic force microscopy–based single-molecule mechanical unfolding methodology to study the conformational equilibrium of human wild-type and mutant αSyn. The conformational heterogeneity of monomeric αSyn was characterized at the single-molecule level. Three main classes of conformations, including disordered and “β-like” structures, were directly observed and quantified without any interference from oligomeric soluble forms. The relative abundance of the “β-like” structures significantly increased in different conditions promoting the aggregation of αSyn: the presence of Cu2+, the pathogenic A30P mutation, and high ionic strength. This methodology can explore the full conformational space of a protein at the single-molecule level, detecting even poorly populated conformers and measuring their distribution in a variety of biologically important conditions. To the best of our knowledge, we present for the first time evidence of a conformational equilibrium that controls the population of a specific class of monomeric αSyn conformers, positively correlated with conditions known to promote the formation of aggregates. A new tool is thus made

  6. Dosimetric and workflow evaluation of first commercial synthetic CT software for clinical use in pelvis

    NASA Astrophysics Data System (ADS)

    Tyagi, Neelam; Fontenla, Sandra; Zhang, Jing; Cloutier, Michelle; Kadbi, Mo; Mechalakos, Jim; Zelefsky, Michael; Deasy, Joe; Hunt, Margie

    2017-04-01

    To evaluate a commercial synthetic CT (syn-CT) software for use in prostate radiotherapy. Twenty-five prostate patients underwent CT and MR simulation scans in treatment position on a 3T MR scanner. A commercially available MR protocol was used that included a T2w turbo spin-echo sequence for soft-tissue contrast and a dual echo 3D mDIXON fast field echo (FFE) sequence for generating syn-CT. A dual-echo 3D FFE B 0 map was used for patient-induced susceptibility distortion analysis and a new 3D balanced-FFE sequence was evaluated for identification of implanted gold fiducial markers and subsequent image-guidance during radiotherapy delivery. Tissues were classified as air, adipose, water, trabecular/spongy bone and compact/cortical bone and assigned bulk HU values. The accuracy of syn-CT for treatment planning was analyzed by transferring the structures and plan from planning CT to syn-CT and recalculating the dose. Accuracy of localization at the treatment machine was evaluated by comparing registration of kV radiographs to either digitally reconstructed radiographs (DRRs) generated from syn-CT or traditional DRRs generated from the planning CT. Similarly, accuracy of setup using CBCT and syn-CT was compared to that using the planning CT. Finally, a MR-only simulation workflow was established and end-to-end testing was completed on five patients undergoing MR-only simulation. Dosimetric comparison between the original CT and syn-CT plans was within 0.5% on average for all structures. The de-novo optimized plans on the syn-CT met institutional clinical objectives for target and normal structures. Patient-induced susceptibility distortion based on B 0 maps was within 1 mm and 0.5 mm in the body and prostate respectively. DRR and CBCT localization based on MR-localized fiducials showed a standard deviation of  <1 mm. End-to-end testing and MR simulation workflow was successfully validated. MRI derived synthetic CT can be successfully used for a MR

  7. Nomenclatural studies toward a world catalog of Diptera genus-group names. III. Christian Rudolph Wilhelm Wiedemann.

    PubMed

    Evenhuis, Neal L; Pont, Adrian C

    2013-01-01

    The Diptera genus-group names of Christian Rudolph Wilhelm Wiedemann are reviewed and annotated. A total of 50 available genus-group names in 25 families of Diptera are listed alphabetically for each name giving author, year and page of original publication, originally included species, type species and method of fixation, current status of the name, family placement, and a list of any emendations of it that have been found in the literature. Remarks are given to clarify nomenclatural or taxonomic information. A biography of Wiedemann is given with discussion of his works and his relationships with contemporaries. In addition, an index is given to all the species-group names of Diptera proposed by Wiedemann (1,775 of which 1,698 are available) with bibliographic reference to each original citation. An appendix gives a complete bibliography of all the known writings by Wiedemann, non-zoological as well as zoological.The following type species is designated herein: Eristalis chrysopygus Wiedemann, 1819 for Pachycephalus Wiedemann, 1830, by present designation [Syrphidae].Corrected or clarified type-species and methods of typification are given for: Colax Wiedemann, 1824 [Nemestrinidae]; Cyphomyia Wiedemann, 1819 [Stratiomyidae]; Philoliche Wiedemann, 1821 [Tabanidae]; Ropalomera Wiedemann, 1820 [Ropalomeridae]; Timia Wiedemann, 1824 [Ulidiidae].Acting as First Reviser, the following correct original spelling for multiple original spellings is selected: Maekistocera Wiedemann, 1820 [Tipulidae]. A previous First Reviser action for multiple original spellings missed by other workers is given for the following: Rhaphiorhynchus Wiedemann, 1821 [Pantophthalmidae].The following nominal genera enter into new synonymies: Ceratophyia Osten Sacken, 1858 of Ceratophya Wiedemann, 1824, n. syn. [Syrphidae]; Epopter Wiedemann, 1830 of Sphecomyia Le Peletier & Serville, 1825, n. syn. [Syrphidae]; Melophaga Wiedemann, 1830 of Melophagus Latreille, 1802, n. syn. [Hippoboscidae]; Midas

  8. Syn-orogenic magmatism over 100 m.y. in high crustal levels of the central Grenville Province: Characteristics, age and tectonic significance

    NASA Astrophysics Data System (ADS)

    Groulier, Pierre-Arthur; Indares, Aphrodite; Dunning, Gregory; Moukhsil, Abdelali; Jenner, George

    2018-07-01

    The Escoumins Supracrustal Belt (ESB) represents higher levels of the infrastructure of a large hot orogen, exposed in a broadly dome and basin pattern. It consists of remnants of a Pinwarian-age (1.52-1.46 Ga) oceanic arc and arc-rift sequence, preserved in the low-P Belt of the central Grenville Province, and was intruded by diverse Grenvillian-age plutons. The plutonic rocks range from quartz monzodiorite to granite and have intrusion ages covering a time interval of 100 My, that represents the entire range of the Grenvillian orogeny. Moreover, the ages, field relations and geochemical signatures of the different intrusions can be matched with different documented stages of the orogeny. The oldest pluton, the magnesian, biotite-bearing Bon-Désir granite (1086 ± 2 Ma), has positive εNd (+0.6), TDM = 1.52 Ga, and is attributed to melting of a juvenile Pinwarian crust as a result of slab break-off, at the onset of continental collision. The ferroan and Ba-Sr enriched, biotite-, amphibole- and clinopyroxene-bearing Michaud plutonic suite (1063 ± 3 Ma) and biotite-rich felsic sill (1045 ± 3 Ma) have εNd (-0.01 - +0.8) and TDM = 1.45-1.48 Ga. Their geochemistry is consistent with fractionation of a mafic magma derived from melting of a Geon 14 subduction-modified subcontinental lithospheric mantle. This magmatism is consistent with convective thinning of subcontinental lithosphere, potentially linked to tectonic extrusion and orogenic collapse. This collapse ultimately led to the juxtaposition of the low-P Belt with the high-T mid-P Belt in the hinterland of the Grenville Province and to amphibolite-facies metamorphism in the former, producing metamorphic zircon overgrowths at 1037 ± 10 Ma. Finally, 988 ± 5 Ma to 983 ± 5 Ma syn-kinematic peraluminous two-mica garnetiferous leucogranite bodies and pegmatites with inherited 1055 ± 2 Ma metamorphic monazite were derived from melting of previously metamorphosed deeper levels of the low-P Belt. This is consistent

  9. Structure and magnetic properties of an unprecedented syn-anti μ-nitrito-1κO:2κO' bridged Mn(III)-salen complex and its isoelectronic and isostructural formate analogue.

    PubMed

    Kar, Paramita; Biswas, Rituparna; Drew, Michael G B; Ida, Yumi; Ishida, Takayuki; Ghosh, Ashutosh

    2011-04-07

    The preparation, crystal structures and magnetic properties of two new isoelectronic and isomorphous formate- and nitrite-bridged 1D chains of Mn(III)-salen complexes, [Mn(salen)(HCOO)](n) (1) and [Mn(salen)(NO(2))](n) (2), where salen is the dianion of N,N'-bis(salicylidene)-1,2-diaminoethane, are presented. The structures show that the salen ligand coordinates to the four equatorial sites of the metal ion and the formate or nitrite ions coordinate to the axial positions to bridge the Mn(III)-salen units through a syn-antiμ-1κO:2κO' coordination mode. Such a bridging mode is unprecedented in Mn(III) for formate and in any transition metal ion for nitrite. Variable-temperature magnetic susceptibility measurements of complexes 1 and 2 indicate the presence of ferromagnetic exchange interactions with J values of 0.0607 cm(-1) (for 1) and 0.0883 cm(-1) (for 2). The ac measurements indicate negligible frequency dependence for 1 whereas compound 2 exhibits a decrease of χ(ac)' and a concomitant increase of χ(ac)'' on elevating frequency around 2 K. This finding is an indication of slow magnetization reversal characteristic of single-chain magnets or spin-glasses. The μ-nitrito-1κO:2κO' bridge seems to be a potentially superior magnetic coupler to the formate bridge for the construction of single-molecule/-chain magnets as its coupling constant is greater and the χ(ac)' and χ(ac)'' show frequency dependence. © The Royal Society of Chemistry 2011

  10. Accumulation of the Cyclobutane Thymine Dimer in Defined Sequences of Free and Nucleosomal DNA

    DTIC Science & Technology

    2013-08-01

    cyclobutane dimer in a single-stranded vector , Proc. Natl. Acad. Sci. U. S. A., 1988, 85, 8141–8145. 11 C. A. Smith, M. Wang, N. Jiang, L. Che, X. Zhao and...J.-S. Taylor, Mutation spectra of M13 vectors cont