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

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.

[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 different function of both structures in the recent primates gives a hint for the possible reason for their development during the process of evolution.

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.

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.

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.

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.

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.

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

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

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 topographic knowledge that a natural plica exists at the anatomic base of the antihelix is a valuable key point in recognizing the normal external ear. In addition, the making of a natural plica is the first and most effective factor in the reconstruction of the antihelical fold and its absolute absence results in the pathologic condition for protruding ears. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A3 online Instructions to Authors. http://www.springer.com/00266 .

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.

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.

[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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

[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. Furthermore 0.2% of the samples contained proglottids of Mesocestoides and 0.2% stages of Dipylidium sp. Eggs of Capillaria sp. were found in 33% of the 106 samples of hedgehogs, larvae of Crenosoma striatum in 27.4%, oocysts of Isospora sp. in 5.7% of the cases. In 232 samples of rabbits 56.9% oocysts of Eimeria sp., 4.8% stages of Passalurus ambiguus, 1.3% of strongylids, 0.9% of Strongyloides sp., 0.4% of trematodes were found.

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.

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.

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...

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. [Tachinidae]; Cyanea Meigen in Hendel, 1908 under Melophagus Latreille, 1802, n. syn. [Hippoboscidae]; Cypsela Meigen in Hendel, 1908 under Sphaerocera Latreille, 1804, n. syn. [Sphaeroceridae]; Dionnaea Meigen in Hendel, 1908 under Rhamphomyia Meigen, 1822, n. syn. [Empididae]; Dorilas Meigen in Hendel, 1908 under Pipunculus Latreille, 1802, n. syn. [Pipunculidae]; Echinodes Meigen in Hendel, 1908 under Eriothrix Meigen, 1803, n. syn. [Tachinidae]; Erinna Hendel, 1903 under Xylophagus Meigen, 1803, n. syn. [Xylophagidae]; Eulalia Hendel, 1903 under Odontomyia Meigen, 1803, n. syn. [Stratiomyidae]; Euphrosyne Meigen in Hendel, 1908 under Macrocera Meigen, 1803, n. syn. [Keroplatidae]; Flabellifera Osten Sacken, 1882 under Tanyptera Latreille, 1804, n. syn. [Tipulidae]; Fungivora Meigen in Hendel, 1908 under Mycetophila Meigen, 1803, n. syn. [Mycetophilidae]; Helea Osten Sacken, 1882 under Ceratopogon Meigen, 1803, n. syn. [Ceratopogonidae]; Hermione Bezzi, 1908 under Oxycera Meigen, 1803, n. syn. [Stratiomyidae]; Itonida Bezzi, 1908 under Cecidomyia Meigen, 1803, n. syn. [Cecidomyiidae]; Lampetia Meigen in Hendel, 1908 under Merodon Meigen, 1803, n. syn. [Syrphidae]; Laphria Bezzi, 1907 under Laphria Meigen, 1803, n. syn. [Asilidae]; Lapria Bezzi, 1907 under Laphria Meigen, 1803, n. syn. [Asilidae]; Larvaevora Meigen in Hendel, 1908 under Tachina Meigen, 1803, n. syn. [Tachinidae]; Liriope Meigen in Hendel, 1908 under Ptychoptera Meigen, 1803, n. syn. [Ptychopteridae]; Lycoria Latreille, 1802 under Sylvicola Harris, 1776, n. syn. [Anisopodidae]; Melusina Meigen in Hendel, 1908 under Trichocera Meigen, 1803, n. syn. [Trichoceridae]; Musidora Meigen in Hendel, 1908 under Lonchoptera Meigen, 1803, n. syn. [Lonchopteridae]; Noeza Meigen in Hendel, 1908 under Hybos Meigen, 1803, n. syn. [Hybotidae]; Omphrale Meigen in Hendel, 1908 under Scenopinus Latreille, 1802, n. syn. [Scenopinidae]; Pales Bezzi, 1906 under Nephrotoma Meigen, 1803, n. syn . [Tipulidae]; Penthesilea Meigen in Hendel, 1908 under Blera Billberg, 1820, n. syn. [Syrphidae]; Petaurista Meigen in Hendel, 1908 under Trichocera Meigen, 1803, n. syn. [Trichoceridae]; Phalaenula Desmarest, 1818 under Psychoda Latreille, 1797, n. syn. [Psychodidae]; Philia Meigen in Hendel, 1908 under Dilophus Meigen, 1803, n. syn. [Bibionidae]; Phryne Meigen in Hendel, 1908 under Sylvicola Harris, 1776, n. syn. [Anisopodidae]; Polymeda Meigen in Hendel, 1908 under Erioptera Meigen, 1803, n. syn. [Limoniidae]; Polyxena Meigen in Hendel, 1908 under Cordyla Meigen, 1803, n. syn. [Mycetophilidae]; Potamida Hendel, 1903 under Clitellaria Meigen, 1803, n. syn. [Stratiomyidae]; Rhodogyne Meigen in Hendel, 1908 under Gymnosoma Meigen, 1803, n. syn. [Tachinidae]; Salmacia Meigen in Hendel, 1908 under Gonia Meigen, 1803, n. syn. [Tachinidae]; Scathophaga Meigen, 1803 under Scopeuma Latreille, 1802, n. syn. [Scathophagidae]; Coremacera Rondani, 1856 under Statinia Latreille, 1802, n. syn. [Sciomyzidae]; Tendipes Meigen in Hendel, 1908 under Chironomus Meigen, 1803, n. syn. [Chironomidae]; Titania Meigen in Hendel, 1908 under Chlorops Meigen, 1803, n. syn. [Chloropidae]; Trepidaria Meigen in Hendel, 1908 under Calobata Meigen, 1803, n. syn. [Micropezidae]; Tritonia Meigen in Hendel, 1908 under Temnostoma Le Peletier & Audinet-Serville, 1828, n. syn. [Syrphidae]; Tubifera Meigen in Hendel, 1908 under Eristalis Latreille, 1804, n. syn. [Syrphidae]; Urophora Robineau-Desvoidy, 1830 under Euribia Latreille, 1802, n. syn. [Tephritidae]; Zelima Hendel, 1903 under Xylota Meigen, 1822, n. syn. [Syrphidae]; Zelmira Meigen in Hendel, 1908 under Orfelia Costa, 1857, n. syn. [Keroplatidae].        The following three names have not been found to be synonymous with any other taxon, and are treated here as nomina dubia: Orithea Meigen in Hendel, 1908; Salpyga Meigen in Hendel, 1908; Titia Meigen in Hendel, 1908 (preoccupied).      The following four names are found to be senior synonyms of more commonly used genus-group names: Euribia Latreille, 1802 of Urophora Robineau-Desvoidy, 1830, n. syn. [Tephritidae]; Pelopia Latreille, 1802 of Ablabesmyia Johannsen, 1905, n. syn.; Scopeuma Latreille, 1802 of Scathophaga Meigen, 1803, n. syn. [Scathophagidae]; Statinia Latreille, 1802 of Coremacera Rondani, 1856, n. syn. [Sciomyzidae]. If they are construed as threatening stability of nomenclature and/or taxonomy, applications to the ICZN Commission may be warranted to request suppression of these names in favor of their junior synonyms.

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.

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.

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.

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.

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.

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

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 ...

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.

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

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.

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.

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.

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

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 strategy for protecting against α-syn-induced toxicity and slowing the progression of neurodegeneration in PD and other synucleinopathies. PMID:26138444

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.

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

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.

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

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

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.

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

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.

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

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.

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

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.

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.

[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.

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.

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.

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 = 0.004) and a higher proportion of α-syn positive distal cells (p = 0.001) than cells exposed to monomeric α-syn. Co-treatment of THP-1 groups with the tubulin depolymerisation inhibitor, Epothilone D (EpoD; 10 nM), was conducted to investigate if inhibition of microtubule activity had an effect on cell migration and residual immobilized α-syn density. There was a significant increase in both residual immobilized α-syn between EpoD treated and non-treated differentiated cells exposed to monomeric (p = 0.037) and aggregated (p = 0.018) α-syn, but not with undifferentiated cells. Differentiated THP-1 cells exposed to immobilized aggregated α-syn showed a significant difference in the proportion of distal aggregate bearing cells between EpoD treated and untreated (p = 0.027). The results suggest microglia could play a role in α-syn transport in MSA, a role which could potentially be inhibited therapeutically by EpoD. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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

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

The Diptera genus-group names of Pierre-Justin-Marie Macquart are reviewed and annotated. A total of 399 available genus-group names in 69 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. In addition, an index to all the species-group names of Diptera proposed by Macquart (3,611, of which 3,543 are available) is given with bibliographic reference (year and page) to each original citation.        The following type species are designated herein: Agculocera nigra Macquart, 1855 for Onuxicera Macquart, 1855, present designation [Tachinidae]; Trixa imhoffi Macquart, 1834, for Semiomyia Macquart, 1848, present designation [Tachinidae].        The following type species are designated herein with fixation under ICZN Code Art. 70.3.2: Azelia nebulosa Robineau-Desvoidy, 1830 for Atomogaster Macquart, 1835, present designation [Muscidae]; Tachydromia vocatoria Fallén, 1816 for Chelipoda Macquart, 1835, present designation [Empididae]; Eriocera macquarti Enderlein, 1912 for Eriocera Macquart, 1838, present designation [Limoniidae]; Limosina acutangula Zetterstedt, 1847 for Heteroptera Macquart, 1835, present designation [Sphaeroceridae]; Phryxe pavoniae Robineau-Desvoidy, 1830 for Masicera Macquart, 1834, present designation [Tachinidae]; Pachymyia macquartii Townsend, 1916 for Pachymyia Macquart, 1844, present designation [Tachinidae].        Earlier valid subsequent type-species designations have been found in this study for the following: Anisophysa Macquart, 1835 [Sepsidae]; Diphysa Macquart, 1838 [Stratiomyidae]; Pachyrhina Macquart, 1834 [Tipulidae]; Silbomyia Macquart, 1844 [Calliphoridae].        One name is raised from synonymy: Czernyola Bezzi, 1907, n. stat. [Clusiidae].        Names previously treated as available but found in this work to be unavailable include the following: Genus-group names-Anodontina Macquart, 1838, n. stat. [Empididae]; Athricia Macquart, 1834, n. stat. [Tachinidae]; Blepharis Macquart, 1838, n. stat. [Asilidae]; Dichelocera Enderlein, 1922, n. stat. [Tabanidae]; Lepidoselaga Loew, 1869, n. stat. [Tabanidae]; Lemptopeza Macquart, 1828, n. stat. [Hybotidae]; Microphora Zetterstedt, 1842, n. stat. [Dolichopodidae]; Microphorus Macquart, 1834, n. stat. [Dolichopodidae]; Plagiocephala Macquart, 1844, n. stat. [Ulidiidae]; Stratiomyia Macquart, 1838, n. stat. [Stratiomyidae]; Taenioptera Agassiz, 1846, n. stat. [Micropezidae]; Tapigaster Bezzi, 1923, n. stat. [Heleomyzidae]; Trizota Macquart, 1829, n. stat. [Syrphidae]. Species-group names-Microstylum sinense Macquart, 1838, n. stat. [Asilidae].        Corrected or clarified included species and/or corrected or clarified type-species and methods of typification are given for: Anabarhynchus Macquart, 1848 [Therevidae]; Anacanthella Macquart, 1855 [Stratiomyidae]; Apeilesis Macquart, 1846 [Tipulidae]; Aplomera Macquart, 1838 [Empididae]; Aprotheca Macquart, 1851 [Tachinidae]; Ardoptera Macquart, 1828 [Empididae]; Blepharella Macquart, 1851 [Tachinidae]; Brachystylum Macquart, 1855 [Tachinidae]; Cadicera Macquart, 1855 [Tabanidae]; Calobatemyia Macquart, 1855 [Calliphoridae]; Catapicephala Macquart, 1851 [Calliphoridae]; Ceroptera Macquart, 1835 [Sphaeroceridae]; Cheligaster Macquart, 1835 [Sepsidae]; Chetogaster Macquart, 1851 [Tachinidae]; Chlorogaster Macquart, 1851 [Tachinidae]; Cleitamia Macquart, 1835 [Platystomatidae]; Craspedia Macquart, 1838 [Asilidae]; Craspedochoeta Macquart, 1851 [Anthomyiidae]; Crumomyia Macquart, 1835 [Sphaeroceridae]; Dasyomma Macquart, 1840 [Athericidae]; Demoticus Macquart, 1854 [Tachinidae]; Epicerella Macquart, 1851 [Pyrgotidae]; Epicerina Macquart, 1850 [Acroceridae]; Euprosopia Macquart, 1847 [Platystomatidae]; Grapholostylum Macquart, 1851 [Tachinidae]; Graphomyzina Macquart, 1835 [Sciomyzidae]; Gymnostylina Macquart, 1835 [Tachinidae]; Heterometopia Macquart, 1846 [Tachinidae]; Laxenecera Macquart, 1838 [Asilidae]; Leptomyza Macquart, 1835 [Anthomyzidae]; Megistogaster Macquart, 1851 [Tachinidae]; Microtrichodes Macquart, 1846 [Tachinidae]; Microtropesa Macquart, 1846 [Tachinidae]; Ogcodocera Macquart, 1840 [Bombyliidae]; Onuxicera Macquart, 1855 [Tachinidae]; Ozodicera Macquart, 1834 [Tipulidae]; Pachymerina Macquart, 1834 [Empididae]; Pachyrhina Macquart, 1834 [Tipulidae]; Pachystylum Macquart, 1848 [Tachinidae]; Physegaster Macquart, 1847 [Acroceridae]; Plesionevra Macquart, 1855 [Tachinidae]; Rhopalia Macquart, 1838 [Mydidae]; Semiomyia Macquart, 1848 [Tachinidae]; Senostoma Macquart, 1847 [Tachinidae]; Silbomyia Macquart, 1844 [Calliphoridae]; Sumpigaster Macquart, 1855 [Tachinidae]; Tapinocera Macquart, 1838 [Apioceridae]; Teretrophora Macquart, 1851 [Tachinidae]; Toxocnemis Macquart, 1855 [Tachinidae]; Toxotarsus Macquart, 1851 [Calliphoridae]; Trichostylum Macquart, 1851 [Tachinidae]; Trigonometopus Macquart, 1835 [Lauxaniidae]; Tritaxys Macquart, 1847 [Tachinidae]; Vermileo Macquart, 1834 [Vermileonidae].        Acting as First Reviser, the following correct original spellings for multiple original spellings are selected by us-(for genus-group names): Choeteprosopa Macquart, 1851 [Tachinidae]; Dichoetometopia Macquart, 1855 [Sarcophagidae]; Discocerina Macquart, 1835 [Ephydridae]; Dolichocephala Macquart, 1823 [Empididae]; Dolichomerus Macquart, 1850 [Syrphidae]; Graphalostylum Macquart, 1851 [Tachinidae]; Hemilampra Macquart, 1850 [Syrphidae]; Leptomyza Macquart, 1835 [Anthomyzidae]; Microcheilosia Macquart, 1855 [Tachinidae]; Phrissopodia Macquart, 1835 [Sarcophagidae]; Platytainia Macquart, 1851 [Tachinidae]; Polychaeta Macquart, 1851 [Tachinidae]; Stachynia Macquart, 1835 [Conopidae]-(for species-group names): Cadicera rubramarginata Macquart, 1855 [Tabanidae].        Previous First Reviser actions for multiple original spellings that were missed by other workers are given for the following: Amethysa Macquart, 1835 [Ulidiidae]; Anabarhynchus Macquart, 1848 [Therevidae]; Anacanthella Macquart, 1855 [Stratiomyidae]; Aulacigaster Macquart, 1835 [Aulacigastridae]; Cardiacera Macquart, 1847 [Pyrgotidae]; Comptosia Macquart, 1840 [Bombyliidae]; Craspedia Macquart, 1838 [Asilidae]; Cyclorhynchus Macquart, 1840 [Bombyliidae]; Ectinorhynchus Macquart, 1850 [Therevidae]; Euthinevra Macquart, 1836 [Hybotidae]; Gonistylum Macquart, 1851 [Tachinidae]; Heterostylum Macquart, 1848 [Bombyliidae]; Hoplistomera Macquart, 1838 [Asilidae]; Hystricephala Macquart, 1846 [Tachinidae]; Leptoxyda Macquart, 1835 [Tephritidae]; Nemopalpus Macquart, 1838 [Psychodidae]; Senotainia Macquart, 1846 [Sarcophagidae]; Spilogaster Macquart, 1835 [Muscidae]; Spogostylum Macquart, 1840 [Bombyliidae]; Stachynia Macquart, 1835 [Conopidae].        Invoking ICZN Code Article 33.3.1, the following is here considered a correct original spelling by being in prevailing usage: Leptopeza Macquart, 1828 [Empididae].        Reversal of Precedence (ICZN Code Article 23.9) is invoked to promote stability in nomenclature for the following cases of subjective synonymy: Atherigona Rondani, 1856, nomen protectum and Orthostylum Macquart, 1851, nomen oblitum [in Muscidae]; Clusiodes Coquillett, 1904, nomen protectum and Heteronevra Macquart, 1835, nomen oblitum [in Clusiidae]; Senotainia Macquart, 1846, nomen protectum and Megoera Macquart, 1834, nomen oblitum [in Sarcophagidae].        The following genus-group names, not listed in current regional catalogs, are treated here: Diasema Macquart, 1835 [Chloropidae]; Dichromyia Macquart, 1844 [Heleomyzidae]; Elomyia Macquart, 1834 [Tachinidae]; Eriosoma Macquart, 1838 [Acroceridae]; Eurypalpus Macquart, 1835 [Platystomatidae]; Notacanthina Macquart, 1835 [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 Peletier & Audinet-Serville, 1828, n. syn. [Muscidae]; Hemerodromyia Macquart, 1823 of Hemerodromia Meigen, 1822, n. syn. [Empididae]; Heteronevra Macquart, 1835 of Clusiodes Coquillett, 1904, n. syn. [Clusiidae]; Himastima Agassiz, 1846 of Mallota Meigen, 1822, n. syn. [Syrphidae]; Hoematopota Macquart, 1826 of Haematopota Meigen, 1803, n. syn. [Tabanidae]; Homalocephala Agassiz, 1846 of Setellia Robineau-Desvoidy, 1830, n. syn. [Sciomyzidae]; Hydrotoea Macquart, 1844 of Hydrotaea Robineau-Desvoidy, 1830, n. syn. [Muscidae]; Linnemyia Macquart, 1834 of Linnaemya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Lonchoea Macquart, 1835 of Lonchaea Fallén, 1820b, n. syn. [Lonchaeidae]; Macromyia Macquart, 1835 of Macromya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Megarhina Macquart, 1838 of Lynchiella Lahille, 1904, n. syn. [Culicidae]; Meriana Macquart, 1835 of Panzeria Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Microphorus Lundbeck, 1907 of Microphor Macquart, 1834, n. syn. [Dolichopodidae]; Nemoroea Macquart, 1844 of Nemoraea Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Ochthiphila Macquart, 1850 of Chamaemyia Meigen, 1803, n. syn. [Chamaemyiidae]; Ocydromyia Macquart, 1823 of Ocydromia Meigen, 1820, n. syn. [Hybotidae]; Oliviera Macquart, 1835 of Eriothrix Meigen, 1803, n. syn. [Tachinidae]; Ophilia Macquart, 1850 of Metopia Meigen, 1803, n. syn. [Sarcophagidae]; Ornithomyia Fischer von Waldheim, 1808 of Ornithomya Latreille, 1802, n. syn. [Hippoboscidae]; Orthochile Westwood, 1840 of Ortochile Latreille, 1809, n. syn. [Dolichopodidae]; Osmoea Macquart, 1834 of Triarthria Stephens, 1829, n. syn. [Tachinidae]; Pachyrrhina Osten Sacken, 1878 of Pachyrhina Macquart, 1834, n. syn. [Tipulidae]; Palis Macquart, 1850 of Pales Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Phanemia Macquart, 1835 of Clairvillia Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Phrissopoda Macquart, 1851 of Peckia Robineau-Desvoidy, 1830, n. syn. [Sarcophagidae]; Phyllomyia Macquart, 1834 of Phyllomya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Physogenia Loew, 1862 of Physegenua Macquart, 1848, n. syn. [Lauxaniidae]; Physogenua Giglio-Tos, 1895 of Physegenua Macquart, 1848, n. syn. [Lauxaniidae]; Phytomiza Macquart, 1835 of Phytomyza Fallén, 1810, n. syn. [Agromyzidae]; Platipalpus Macquart, 1850 of Platypalpus Macquart, 1828, n. syn. [Hybotidae]; Platipeza Macquart, 1850 of Platypeza Meigen, 1803, n. syn. [Platypezidae]; Platynochoetus Macquart, 1834 of Platynochaetus Wiedemann, 1830 [Syrphidae]; Porphirops Macquart, 1838 of Porphyrops Meigen, 1824, n. syn [Dolichopodidae]; Rhinomyia Macquart, 1835 of Rhinomya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Rhynomyia Macquart, 1834 of Rhinomya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Scathopse Guérin-Méneville, 1839 of Scatopse Geoffroy, 1762, n. syn. [Scatopsidae]; Spherophoria Macquart, 1850 of Sphaerophoria Le Peletier & Audinet-Serville, 1828, n. syn. [Syrphidae]; Sphoerophoria Macquart, 1829 of Sphaerophoria Le Peletier & Audinet-Serville, 1828, n. syn. [Syrphidae]; Stenopteryx Schiner, 1864 of Stenepteryx Leach, 1817, n. syn. [Hippoboscidae]; Stenostoma Mik, 1890 of Senostoma Macquart, 1847, n. syn. [Tachinidae]; Tachydromyia Macquart, 1823 of Tachydromia Meigen, 1803, n. syn. [Hybotidae]; Taenioptera Mik, 1898 of Taeniaptera Macquart, 1835, n. syn. [Micropezidae]; Trinevra Macquart, 1835 of Phora Latreille, 1797, n. syn. [Phoridae]; Uramyia Macquart, 1844 of Uramya Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Xestomysa Macquart, 1851 of Xestomyza Wiedemann, 1820, n. syn. [Therevidae]; Zygonevra Macquart, 1834 of Zygoneura Meigen, 1803, n. syn. [Sciaridae]. -Species-group names: Calobatemyia nigra Macquart, 1855 of Musca doronici Scopoli, 1763, n. syn. [Calliphoridae]; Cyrtonevra protorum Macquart, 1850 of Musca pratorum Meigen, 1826, n. syn. [Muscidae]; Eumerus oeneus Macquart, 1850 of Eumerus aeneus Macquart, 1829, n. syn. [Syrphidae]; Lucilia ceserion Macquart, 1850 of Musca caesarion Scharfenberg, 1805, n. syn. [Calliphoridae]; Masicera sylvatica Macquart, 1850 of Tachina silvatica Fallén, 1810, n. syn. [Tachinidae]; Ophyra anolis Macquart, 1850 of Ophyra analis Macquart, 1846, n. syn. [Muscidae]; Pegomyia hyosciami Macquart, 1850 of Musca hyoscyami Panzer, 1798, n. syn. [Anthomyiidae]; Prosena syberita Macquart, 1850 of Stomoxys siberita Fabricius, 1775, n. syn. [Tachinidae]; Taxigramma heteronevra Macquart, 1850 of Miltogramma heteroneura Meigen, 1830, n. syn. [Sarcophagidae].

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

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

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

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

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 ubiquitin ligase activity with implications for CHIP-mediated regulation of α-syn oligomerization. PMID:21358815

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. (=Argyrobrithes curtilamellatum (Lindner, 1966)), Microptecticus clarus Lindner, 1968 syn. nov. (=Microptecticus ambiguus Lindner, 1966b), Neopachygaster umbrifera Lindner, 1966a syn. nov. (=Neopachygaster stigma Lindner, 1938), Odontomyia impressa Curran, 1928 syn. nov. (=Afrodontomyia gigas (Brunetti, 1926)), Odontomyia protrudens Curran, 1928 syn. nov. (=Afrodontomyia erecta (Brunetti, 1926)), Physometopon minor Lindner, 1968 syn. nov. (=Cardopomyia robusta Kertész, 1916), Platyna denudata Grünberg, 1915 syn. nov. (=Platyna hastata (Fabricius, 1805)), Ptectisargus lucidus Lindner, 1968 syn. nov. (=Ptectisargus abditus (Lindner, 1936)); Afrodontomyia erecta (Brunetti, 1926) comb. nov. (from Odontomyia), Afrodontomyia flammiventris (Brunetti, 1926) comb. nov. (from Odontomyia), Afrodontomyia rufiventris (Curran, 1928) comb. nov. (from Stratiomys), Argyrobrithes curtilamellatum (Lindner, 1966b) comb. nov. (from Arthronemina), Argyrobrithes fuscicornis (Bezzi, 1914) comb. nov. (from Sternobrithes), Cardopomyia parvicornis (Lindner, 1959) comb. nov. (from Pseudoxymyia Lindner, 1958), Cardopomyia vesicularis (Lindner, 1966b) comb. nov. (from Physometopon), Cephalochrysa bigoti (Lindner, 1968) comb. nov. (from Chrysochroma), Cephalochrysa flavum (Lindner, 1968) comb. nov. (from Chrysochroma), Cephalochrysa fortunatum (Lindner, 1966b) comb. nov. (from Chrysochroma), Cephalochrysa lapidis (Lindner, 1966b) comb. nov. (from Chrysochroma), Cephalochrysa latum (Lindner, 1966b) comb. nov. (from Chrysochroma), Cephalochrysa lucens (Lindner, 1968) comb. nov. (from Chrysochroma), Cephalochrysa matilei (Lindner, 1979) comb. nov. (from Chrysochroma), Cephalochrysa triste (Lindner, 1966b) comb. nov. (from Chrysochroma), Cephalochrysa turbidum (Lindner, 1965) comb. nov. (from Chrysochroma), Cephalochrysa vadoni (Lindner, 1966b) comb. nov. (from Chrysochroma), Gongrosargus flavipennis (Macquart, 1838) comb. nov. (from Sargus), Gongrosargus lateritius (Lindner, 1968) comb. nov. (from Dinosargus), Gongrosargus limbatus (Macquart, 1838) comb. nov. (from Sargus), Gongrosargus pallidus (Macquart, 1838) comb. nov. (from Sargus), Hypoceromys nigripes (Lindner, 1938) comb. nov. (from Pachygaster), Hypoceromys jamesi (Lindner, 1965) comb. nov. (from Meristomeringella), Microptecticus magnicornis (Lindner, 1936) comb. nov. (from Ptecticus), Microptecticus nigricoxa (Lindner, 1936) comb. nov. (from Microchrysa), Ptecticus lateritius (Rondani, 1863) comb. nov. (from Sargus), Ptectisargus abditus (Lindner, 1936) comb. nov. (from Ptecticus), Ptectisargus brunneus (Lindner, 1936) comb. nov. (from Ptecticus), Ptectisargus cingulatum (Lindner, 1968) comb. nov. (from Chrysochroma), Ptectisargus flavifrons (Lindner, 1968) comb. nov. (from Chrysochroma), Ptectisargus flavomarginatus (Loew, 1857) comb. nov. (from Chrysonotus), Ptectisargus gracilipes (Lindner, 1936) comb. nov. (from Ptecticus), Ptectisargus keiseri (Lindner, 1966b) comb. nov. (from Chrysochroma), Ptectisargus longestylum (Lindner, 1966b) comb. nov. (from Chrysochroma), Ptectisargus punctum (Lindner, 1968) comb. nov. (from Chrysochroma), Ptectisargus ranohira (Woodley, 2001) comb. nov. (from Chrysochroma), Ptectisargus unicolor (Lindner, 1968) comb. nov. (from Chrysochroma), Ptilinoxus interruptum (Lindner, 1966b) comb. nov. (from Leucacron), Sargus congoense (Lindner, 1965) comb. nov. (from Chrysochroma), Sargus flavipes (Lindner, 1966a) comb. nov. (from Chrysochroma), Sargus luctuosus (Lindner, 1938) comb. nov. (from Paraptecticus), Sargus opulentum (Grünberg, 1915) comb. nov. (from Chrysochroma), Sargus pallidiventre (Brunetti, 1926) comb. nov. (from Chrysochroma), Sargus ptecticoideum (Lindner, 1966a) comb. nov. (from Chrysochroma), Steleceromys procera (Lindner, 1966a) comb. nov. (from Psapharomydops), Sternobrithes mercurialis (Lindner, 1938) comb. nov. (from Gobertina), Sternobrithes picticornis (Bigot, 1879b). comb. nov. (from Gobertina), Thorasena pectoralis (Wiedemann, 1824) comb. nov. (from Hermetia), Thorasena fenestrata (James, 1949) comb. nov. (from Dolichodema). One genus was resurrected out of synonymy (Thorasena Macquart, 1838 stat. rev.) and one genus removed from the African fauna (Cyphomyia Wiedemann, 1819).

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

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 show that a novel vaccination modality combining an antigen-presenting cell-targeting glucan particle (GP) vaccine delivery system with encapsulated antigen (α-synuclein) + rapamycin (RAP) induced both strong anti-α-synuclein antibody titers and regulatory T cells (Tregs). This vaccine, collectively termed GP+RAP/α-syn, is capable of triggering neuroprotective Treg responses in synucleinopathy models, and the combined vaccine is more effective than the humoral or cellular immunization alone. Together, these results support the further development of this multifunctional vaccine approach for the treatment of synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies, and multiple systems atrophy. Copyright © 2018 the authors 0270-6474/18/381000-15$15.00/0.

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

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.

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

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.

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, 1913, syn. n. and Paragonyleptes simoni Roewer, 1930, syn. n.; Gonyleptes pustulatus Sørensen, 1884 = Gonyleptes guttatus Roewer, 1917, syn. n.; Haversia defensa (Butler, 1876) = Sadocus vallentini Hogg, 1913, syn. n.; Liogonyleptoides minensis (Piza, 1946) = Currala bahiensis Soares, 1972, syn. n.; Megapachylus grandis Roewer, 1913 = Metapachyloides almeidai Soares & Soares, 1946, syn. n.; Mischonyx cuspidatus (Roewer, 1913) = Gonazula gibbosa Roewer, 1930 syn. n.; Mischonyx scaber (Kirby, 1819) = Xundarava holacantha Mello-Leitão, 1927, syn. n.; Parampheres tibialis Roewer, 1917 = Metapachyloides rugosus Roewer, 1917, syn. n.; Parapachyloides uncinatus (Sørensen, 1879) = Goyazella armata Mello-Leitão, 1931, syn. n.; Pseudopucrolia mutica (Perty, 1833) = Meteusarcus armatus Roewer, 1913, syn. n. The following new combinations are proposed: Acrographinotus ornatus (Roewer, 1929), comb. n. (ex Unduavius); Gonyleptellus bimaculatus (Sørensen, 1884),comb. n. (ex Gonyleptes);Gonyleptes perlatus (Mello-Leitão, 1935), comb. n. (exMoojenia);Mischonyx scaber (Kirby, 1819), comb. n. (ex Gonyleptes); and Neopachyloides peruvianus (Roewer, 1956), comb. n. (ex Ceropachylus). The following species of Gonyleptidae, Gonyleptinae are revalidated: Gonyleptes atrus Mello-Leitão, 1923 and Gonyleptes curvicornis (Roewer, 1913). PMID:22707905

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.

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.

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.

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

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.

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 is able to interact with and reduce the activity of VMAT2 and DAT. The resulting dysregulation of dopamine levels directly contributes to the formation of toxic α-Syn oligomers. Together these data suggest a vicious cycle of accumulating α-Syn and deregulated dopamine that triggers synaptic dysfunction and impaired neuronal communication, ultimately causing synaptopathy and progressive neurodegeneration in Parkinson's disease. PMID:29515354

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 gen. rev. (= Aethiopopone syn. n., Nothosphinctus syn. n.). PMID:27559303

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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

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 evidence that loss of α-syn function within nigrostriatal neurons initiates a neuronal-mediated neuroinflammatory cascade, involving both the innate and adaptive immune systems, which ultimately results in the death of affected neurons. PMID:29497361

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.

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

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

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...

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.

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, 1992, syn. nov.), L. silvaticum Hushcha and Schluger, 1967 (= L. pakistanum Vercammen-Grandjean and Langston, 1976, syn. nov.), L. cricethrionis Wen, Sun and Sun, 1984 (= L. rusticum Yu, Yang and Gong, 1986, syn. nov.), L. intermedium (Nagayo, Mitamura and Tamiya, 1920) (= Trombicula (L.) daisen Kumada and Sasa, 1953, syn. nov.; = Trombicula hiranumai Kanda, 1942, syn. nov.), L. fletcheri (Womersley and Heaslip, 1943) (= L. fletcheri fran-colini Wen and Xiang, 1984b, syn. nov.), L. apertum Kudryashova, 1979 (= L. sorosi Kharadov, 1995, syn. nov.; = L. tolaicus Kharadov, 2000, syn. nov.), L. turdicola Vercammen-Grandjean and Langston, 1976 (= L. muntiaci Xiang and Wen, 1984d, syn. nov.; = L. suense Wen, 1984g, syn. nov.), L. paradux Vercammen-Grandjean and Langston, 1976 (= L. montanum Stekolnikov, 2004, syn. nov.), L. hubeiense (Wang, Li and Shi, 1989) comb. nov. from Hsuella, L. dunqingi (Liu, Xiang and Ma, 2003) comb. nov. from Hsuella, L. nainae (Kharadov, 1990) comb. nov. from Montivagum, L. mon-golicum (Kudryashova, 1988) comb. nov. from Montivagum, L. kunitzkyi (Kudryashova, 1988) comb. nov. from Monti-vagum, L. alaicum (Kharadov, 1994) comb. nov. from Montivagum, and Lorillatum nudisensillum (Yu, Gong and Tao, 1981) comb. nov. from Leptotrombidium. A key to Leptotrombidium species is provided.

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.

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

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 nematode infection. This effect was evident for strongyles (P<0.0001) and Capillaria sp. nematodes (P=0.0065). The results of our study suggest that control measures applicable in domestic cattle and small ruminants might be similarly applicable for controlling gastrointestinal nematode infections in captive farmed elands. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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

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.

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.

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

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.

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 Syn-3, respectively; this underlies Syn-4's role in mediating portions of first-phase and second-phase GSIS.

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 di-tyrosine dimers. Our findings uncover a complex interplay between S129 phosphorylation and C-terminal tyrosine modifications of αSyn that likely participates in PD pathology. PMID:27341336

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 di-tyrosine dimers. Our findings uncover a complex interplay between S129 phosphorylation and C-terminal tyrosine modifications of αSyn that likely participates in PD pathology.

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 α-synuclein function at the presynaptic terminal, following sequestration of functional forms of α-synuclein into aggregates. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

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 pharmacological mGluR5 inhibitors such as 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) attenuated the toxic effects of Aβ in α-syn-expressing neuronal cells. Conclusions Together, these results support the possibility that vulnerability of hippocampal neurons to α-syn and Aβ might be mediated via mGluR5. Moreover, therapeutical interventions targeting mGluR5 might have a role in DLB. PMID:24885390

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.

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

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.

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.

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

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.

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

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

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.

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.

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.

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.

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

The types of thirty-two nominal weevil species described by Johann Christian Fabricius are reviewed and lecto- and paralectotypes are designated for twenty-two of them. A neotype is designated for Curculiosticticus Fabricius, 1777. Protapionvaripes (Germar, 1817) is declared a nomen protectum over Curculioflavipes Fabricius, 1775. Based on a study of syntypes, Rhinomacercurculioides Fabricius, 1781 is confirmed as a member of Mycterus (Mycteridae), Bruchusundatus Fabricius, 1787 is tentatively transferred to Erotylidae, Curculiofulvirostris Fabricius, 1787 and Anthribusroboris Fabricius, 1798 are confirmed as members of Salpingus (Salpingidae), and Brachyceruscristatus Fabricius, 1798 is transferred to Tenebrionidae. Based on lectotype designation, Curculiocaninus Fabricius, 1792 is confirmed as a synonym of Sitonalineatus (Linnaeus, 1758) and Curculioinnocuus Fabricius, 1802 as a synonym of Cneorhinusbarcelonicus (Herbst, 1797). Bruchusrufipes Fabricius, 1792 is not considered an available species name, but a later use of Bruchusrufipes Olivier, 1790. Cossonusincisus Pascoe, 1885 is reinstated as valid from synonymy under Cossonusilligeri Champion, 1909 and Cossonusvulneratus Illiger, 1805 from synonymy under Cossonuscanaliculatus (Fabricius, 1792) (a primary homonym of Curculiocanaliculatus Olivier, 1791). Cossonuscanaliculatus Fabricius, 1802 is a secondary homonym of the former and is replaced with Cossonusincisus. Salpingusfulvirostris (Fabricius, 1787) is reinstated as valid from synonymy under Salpingusplanirostris (Fabricius, 1787), a primary homonym of Curculioplanirostris Piller & Mitterpacher, 1783. The following new combinations are proposed: Brachysomuserinaceus (Fabricius, 1802) (from Curculio), Bronchusferus (Gyllenhal, 1840) (from Hipporhinus), Bronchusglandifer (Fabricius, 1792) (from Curculio), Bronchusnivosus (Sparrman, 1785) (from Curculio), Bronchussparrmani (Gyllenhal, 1833) (from Hipporhinus), Coelocephalapionatrirostre (Fabricius, 1802) (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.

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. Second, the results demonstrate that a synaptogenic process that controls excitatory inputs to both pyramidal neurons and interneurons can balance excitation and inhibition. Specifically, the study reveals that hippocampal CA3 connectivity is modulated by the synapse-organizing adhesion protein SynCAM 1 and identifies a novel, SynCAM 1-dependent mechanism that controls excitatory inputs onto parvalbumin-positive interneurons. This enables SynCAM 1 to regulate feedforward inhibition and set network excitability. Further, we show that diffusion tensor imaging is sensitive to these cellular refinements affecting neuronal connectivity. Copyright © 2016 the authors 0270-6474/16/367465-12$15.00/0.

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.

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.

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

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

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

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.

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.

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.

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

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

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

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.

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.

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.

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.

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

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.

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

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

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.

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.

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.

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

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

The Diptera genus-group names of Charles Henry Tyler Townsend are reviewed and annotated. A total of 1506 available genus-group names in 12 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 and/or taxonomic information. In addition, an index to all the species-group names of Diptera proposed by Townsend (1595, of which 1574 are available names) is given with bibliographic reference (year and page) to each original citation. An appendix with a full bibliography of almost 650 papers written by Townsend is presented with accurate dates of publication.        Two new replacement names are proposed for preoccupied genus-group names and both are named to honor our good friend and colleague, James E. O'Hara, for his decades of work on tachinids: Oharamyia Evenhuis, Pont & Whitmore, n. name, for Lindigia Townsend, 1931 [Tachinidae] (preoccupied by Karsten, 1858); Jimimyia Evenhuis, Pont & Whitmore, n. name, for Siphonopsis Townsend, 1916 [Tachinidae] (preoccupied by Agassiz, 1846).        Earlier dates of availability are found for the following: Eucnephalia Townsend, 1892 [Tachinidae]; Gabanimyia Townsend, 1914 [Tachinidae]; Incamyia Townsend, 1912 [Tachinidae]; Muscopteryx Townsend, 1892 [Tachinidae]; Philippolophosia Townsend, 1927 [Tachinidae]; Pseudokea Townsend, 1927 [Tachinidae].        Corrected or clarified included species and/or corrected or clarified type-species and methods of typification are given for: Alitophasia Townsend, 1934 [Tachinidae]; Almugmyia Townsend, 1911 [Tachinidae]; Arachnidomyia Townsend, 1934 [Sarcophagidae]; Austenina Townsend, 1921 [Glossinidae]; Austrohartigia Townsend, 1937 [Sarcophagidae]; Awatia Townsend, 1921 [Muscidae]; Azygobothria Townsend, 1911 [Tachinidae]; Brachymasicera Townsend, 1911 [Tachinidae]; Calocarcelia Townsend, 1927 [Tachinidae]; Cnephalodes Townsend, 1911 [Tachinidae]; Cyacyrtoneura Townsend, 1931 [Muscidae]; Cyrtoneuropsis Townsend, 1931 [Muscidae]; Cyrtosoma Brauer & Bergenstamm, 1893 [Tachinidae]; Epiphyllophila Townsend, 1927 [Tachinidae]; Eucalodexia Townsend, 1892 [Tachinidae]; Eumesembrina Townsend, 1908 [Muscidae]; Eumyobia Townsend, 1911 [Tachinidae]; Eusisyropa Townsend, 1908 [Tachinidae]; Gabanimyia Townsend, 1914 [Tachinidae]; Galactomyia Townsend, 1908 [Tachinidae]; Girschneria Townsend, 1919 [Tachinidae]; Gymnochaetopsis Townsend, 1914 [Tachinidae]; Himantostomopsis Townsend, 1921 [Tachinidae]; Incamyia Townsend, 1912 [Tachinidae]; Lithoexorista Townsend, 1921 [Tachinidae]; Muscopteryx Townsend, 1892 [Tachinidae]; Myocuphocera Townsend, 1931 [Tachinidae]; Myxexoristops Townsend, 1911 [Tachinidae]; Neojurinia Townsend, 1914 [Tachinidae]; Newsteadina Townsend, 1921 [Glossinidae]; Ommasicera Townsend, 1911 [Tachinidae]; Ophirion Townsend, 1911 [Tachinidae]; Ophiriodexia Townsend, 1911 [Tachinidae]; Ophiriosturmia Townsend, 1911 [Tachinidae]; Opsozelia Townsend, 1919 [Tachinidae]; Paleotachina Townsend, 1921 [Tachinidae]; Palexorista Townsend, 1921 [Tachinidae]; Phasiatacta Townsend, 1911 [Tachinidae]; Philippolophosia Townsend, 1927 [Tachinidae]; Phrissopolia Townsend, 1908 [Tachinidae]; Pseudokea Townsend, 1927 [Tachinidae]; Pygocalcager Townsend, 1935 [Tachinidae]; Trichobius Townsend, 1891 [Hippoboscidae]; Villeneuvia Townsend, 1921 [Tachinidae]; Zonoepalpus Townsend, 1927 [Tachinidae]; Zygosturmia Townsend, 1911 [Tachinidae].        The following names previously treated as available are shown to be unavailable.-Genera: Denatella Townsend, 1931, n. stat. [Calliphoridae]; Epseudocyptera Townsend, 1927, n. stat. [Tachinidae]; Eustomatodexia Townsend, 1892, n. stat. [Tachinidae].-Species: Epseudocyptera epalpata Townsend, 1927, n. stat. [Tachinidae]; 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-Desvoidy, 1830, n. syn. [Muscidae]; Kurintjimyia Townsend, 1926 under Tachina Meigen, 1803, n. syn. [Tachinidae]; Labidigaster Macquart, 1844 under Labigastera Macquart, 1834, n. syn. [Tachinidae]; Mellanactia Guimarães, 1971 under Oxynops Townsend, 1912, n. syn. [Tachinidae]; Ochromia Townsend, 1935 under Bengalia Robineau-Desvoidy, 1830, n. syn. [Tachinidae]; Pachyrrhina Osten Sacken, 1881 under Nephrotoma Meigen, 1803, n. syn. [Tipulidae]; Procraspedothrix Townsend, 1932 under Phytomyptera Rondani, 1844, n. syn. [Tachinidae]; Pseudogymnosoma Townsend, 1918 under Neomyia Walker, 1859, n. syn. [Muscidae]; Pseudoservillia Townsend, 1916 under Tachina Meigen, 1803, n. syn. [Tachinidae]; Rhymosia Mik, 1886 under Rymosia Winnertz, 1863, n. syn. [Mycetophilidae]; Rhynchomyia Macquart, 1835 under Rhyncomya Robineau-Desvoidy, 1830, n. syn. [Rhiniidae]; Servillioides Townsend, 1926 under Tachina Meigen, 1803, n. syn. [Tachinidae]; Servilliopsis Townsend, 1916 under Tachina Meigen, 1803, n. syn. [Tachinidae]; Stephanostoma Cole, 1923 under Bercaea Robineau-Desvoidy, 1863, n. syn. [Sarcophagidae]; Stomatorhinia Townsend, 1935 under Stomorhina Rondani, 1861, n. syn. [Rhiniidae]; Toxorrhina Osten Sacken, 1869 under Toxorhina Loew, 1850, n. syn. [Limoniidae]; Trichoneura Townsend, 1935 under Stevenia Robineau-Desvoidy, 1830, n. syn. [Rhinophoridae]; Trichopticus Schnabl, 1889 under Thricops Rondani, 1856, n. syn. [Muscidae]; Tricyclopsis Townsend, 1916 under Paracalliphora Townsend, 1916, n. syn. [Calliphoridae].

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 Master research agreement with Philips healthcare.« less

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.

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

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.

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.

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

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.

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.

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

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.

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 with other proteins and/or biological membranes. PMID:22315227

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.

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

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.

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.

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.

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.

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

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).

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.

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

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.

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

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.

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

A catalogue of butterflies of Russia and adjacent countries is given, with special account to the name-bearing types depository. This catalogue contains data about 86 species (3 of them are questionable) of Hesperiidae (22 genera); 47 species of Papilionidae (14 genera); 89 species of Pieridae (5 of them are questionable)  (15 genera); 1 species (1 genus) of Libytheinae(dae); 2 species of Danainae(dae) (2 genera); 160 species of Nymphalinae(dae) (1 of them is questionable) (23 genera); 259 species of Satyrinae(dae) (14 of them are questionable, mainly from genera Oeneis and Pseudochazara) (34 genera); 3 species of Riodinidae (2 genera); 318 species of Lycaenidae (11 of them are questionable, mainly from genera Neolycaena and Plebeius) (57 genera). In total: 965 species of butterflies, 174 genera, by countries: Armenia-244, Azerbaijan-225, Belarus-107, Estonia-113, Georgia-211, Kyrgyzstan-316, Kazakhstan-344, Latvia-115, Lituania-126, Moldova-87, Russia-522, Tajikistan-295, Turkmenistan-159, Ukraine-192, Uzbekistan-241. Detailed distribution and subspecific structure (if present) for every species is provided. Lectotypes of the following species-group taxa are designated: Hesperia poggei Lederer, 1858, Parnassius felderi Bremer, 1861, P. eversmanni Eversmann, 1851, P. boedromius Püngeler, 1901, Limenitis moltrechti Kardakov, 1928, L. sydyi Kindermann, 1853, L. amphyssa Ménétriès, 1859, L. doerriesi Staudinger, 1892, L. helmanni duplicata Staudinger, 1892, L. homeyeri Tancré, 1881, Argynnis penelope Staudinger, 1891, A. thore borealis Staudinger, 1861, Vanessa io geisha Stichel, [1908], Melitaea maturna staudingeri Wnukowsky, 1929 (=uralensis Staudinger, 1871), M. didymina Staudinger, 1895, Papilio fascelis Esper, 1783, Thecla quercivora Staudinger, 1887, Lycaena orion var. ornata Staudinger, 1892. The following nomenclatural acts are established: Neolycaena submontana baitenovi (Zhdanko, 2011), comb. et stat.n. The following new synonymy is provided: Hesperia 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.

Taxonomic revision of Afrotropical Laccophilus Leach, 1815 (Coleoptera, Dytiscidae)

PubMed Central

Biström, Olof; Nilsson, Anders N.; Bergsten, Johannes

2015-01-01

Abstract The African species of the genus Laccophilus Leach, 1815, are revised, on the basis of study of adult specimens. In all, 105 species are now recognized. A phenetic character-analysis was undertaken, which resulted in a split of the genus into 17 species groups. Diagnoses and a description of each species are given together with keys for identification of species groups and species. We also provide habitus photos, illustration of male genitalia and distribution maps for all species. New species are described as follows: Laccophilus grossus sp. n. (Angola, Namibia), Laccophilus rocchii sp. n. (Tanzania, Namibia, Botswana, Mozambique), Laccophilus ferrugo sp. n. (Mozambique), Laccophilus furthi sp. n. (Madagascar), Laccophilus isamberti sp. n. (Madagascar), Laccophilus inobservatus sp. n. (Gambia, Senegal, Mali, Niger, Sudan, Chad, Ethiopia, Burkina Faso, Ivory Coast, Ghana, Nigeria, Cameroon, Zaire and Asia: Yemen), Laccophilus cryptos sp. n. (Zaire, Mozambique, Zimbabwe, Namibia, Botswana, South Africa), Laccophilus enigmaticus sp. n. (Nigeria, Sudan), Laccophilus bellus sp. n. (Benin, Nigeria), Laccophilus guentheri sp. n. (Guinea, Ghana), Laccophilus guineensis sp. n. (Guinea), Laccophilus decorosus sp. n. (Uganda), Laccophilus empheres sp. n. (Kenya), Laccophilus inconstans sp. n. (Guinea, Ivory Coast, Ghana, Nigeria, Cameroon), Laccophilus brancuccii sp. n. (Central African Republic), Laccophilus incomptus sp. n. (Cameroon), Laccophilus australis sp. n. (Tanzania, South Africa), Laccophilus minimus sp. n. (Namibia), Laccophilus eboris sp. n. (Ivory Coast), Laccophilus insularum sp. n. (Madagascar), Laccophilus occidentalis sp. n. (Gambia, Senegal, Mali, Guinea, Sierra Leone, Ivory Coast, Ghana, Benin, Nigeria, Central African Republic, Zaire) and Laccophilus transversovittatus sp. n. (Madagascar). Laccophilus restrictus Sharp, 1882, is restored as good species; not junior synonym of Laccophilus pictipennis Sharp, 1882. New synonyms are established as 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, 1882, Laccophilus rivulosus Klug, 1833, Laccophilus ampliatus Régimbart, 1895, Laccophilus pilitarsis Régimbart, 1906, Laccophilus adspersus Boheman, 1848, Laccophilus livens Régimbart, 1895, Laccophilus modestus Régimbart, 1895, Laccophilus nodieri Régimbart, 1895, Laccophilus flaveolus Régimbart, 1906, Laccophilus pallescens Régimbart, 1903, Laccophilus restrictus Sharp, 1882, Laccophilus vermiculosus Gerstaecker, 1867, Laccophilus mocquerysi Régimbart, 1895, Laccophilus bizonatus Régimbart, 1895, Laccophilus tschoffeni Régimbart, 1895, Laccophilus persimilis Régimbart, 1895, Laccophilus poecilus Klug, 1834, Laccophilus lateralis Sharp, 1882, Laccophilus lateralis var. polygrammus Régimbart, 1903, Laccophilus cyclopis Sharp, 1882, Laccophilus shephardi Omer-Cooper, 1965, Laccophilus conjunctus Guignot, 1950, Laccophilus grammicus Sharp, 1882, Laccophilus flavoscriptus Régimbart, 1895, Laccophilus flavosignatus Régimbart, 1895, Laccophilus brevicollis Sharp, 1882, Laccophilus secundus Régimbart, Laccophilus desintegratus Régimbart, 1895, Laccophilus gutticollis Régimbart, 1895, Laccophilus luctuosus Sharp, 1882 and Laccophilus inornatus Zimmermann, 1926. Laccophilus remex Guignot, 1952, comprises a species complex with uncertain taxonomic delimitation; the complex includes Laccophilus concisus Guignot, 1953, Laccophilus turneri Omer-Cooper, 1957 and Laccophilus praeteritus Omer-Cooper, 1957, as tentative synonyms of Laccophilus remex Guignot, 1952. PMID:26798285

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...

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).

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.

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

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).

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.

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.

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

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.

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.

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).

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.

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

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

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...

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

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

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.

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

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.

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.

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.

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

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.

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.

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

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.

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.

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. Conclusion: DRRs generated via synCT agreed well with CT-SIM. Planar and volumetric registrations to synCT-derived targets were comparable to CT. This validation is the next step toward clinical implementation of MR-only planning for the brain. The submitting institution has research agreements with Philips Healthcare. Research sponsored by a Henry Ford Health System Internal Mentored Grant.« less

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.

[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.

[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.

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

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

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.

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

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…

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 Malaise, 1945; Allantus eburneus Mocsáry, 1909; Allantus eburneus Mocsáry, 1909; Allantus fulvicornis Mocsáry, 1909; Tenthredo fulvicornis Mocsáry, 1909; Allantus fulvipennis Mocsáry, 1909; Tenthredo fulviventris Mocsáry, 1909; Tenthredo gribodoi Konow, 1898; Allantus lateralis Mocsáry, 1909; Allantus limbiferus Mocsáry, 1891; Allantus moestus Mocsáry, 1883; Rhogogastera nigrita Mocsáry, 1909; Allantus obesus Mocsáry, 1880; Macrophya prasinipes Konow, 1891; Tenthredo punctulata Konow, 1887; Allantus rufipes Mocsáry, 1909; Allantus sabariensis Mocsáry, 1880; Allantus sanguinolentus Mocsáry, 1909; Allantus temulus var. scutellatus Mocsáry, 1909; Allantus testaceus Mocsáry, 1909; Allantus variabilis Mocsáry, 1909. The first records of Tenthredo concinna for Vietnam and Nepal are given.

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

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.

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.

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.

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.

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.

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...

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...

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...

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...

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...

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.

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.

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

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

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

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 significant correlation was observed between decreasing GCase activity and increasing p129S-α-syn. Together our findings indicate α-Gal A deficiency in late-stage PD brain that correlates significantly with the pathological accumulation of α-syn, and further suggest the potential for α-Gal A and its glycosphingolipid substrates as putative biomarkers for PD. Copyright © 2017 Elsevier Inc. All rights reserved.

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 for rectal cancer using MR generated synCT.

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-JEM appeared to be plausible compared with (historical) levels described in the literature. Decisions taken in the development of SYN-JEM did not critically change the cumulative exposure levels. The influence of region-specific estimates needs to be explored in future risk analyses.

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.

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.

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.

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.

Effect of dewatering and composting on helminth eggs removal from lagooning sludge under semi-arid climate.

PubMed

El Hayany, Bouchra; El Glaoui, Ghizlen El Mezouari; Rihanni, Mohammed; Ezzariai, Amine; El Faiz, Abdelouahed; El Gharous, Mohamed; Hafidi, Mohamed; El Fels, Loubna

2018-04-01

In this work, we assessed the drying and composting effectiveness of helminth eggs removal from sewage sludge of a lagoon wastewater treatment plant located in Chichaoua city. The composting was run after mixing sludge with green waste in different proportions: M1 (½ sludge + ½ green waste), M2 ([Formula: see text] sludge + [Formula: see text] green waste), and M3 ([Formula: see text] sludge + [Formula: see text] green waste) for 105 days. The analysis of the dewatered sewage sludge showed a load of 8-24 helminth eggs/g of fresh matter identified as Ascaris spp. eggs (5-19 eggs/g) followed by Toxocara spp. (0.2 to 2.4 eggs/g); Hookworm spp. and Capillaria spp. (0.4-1 egg/g); Trichuris spp., Taenia spp., and Shistosoma spp. (< 1 egg/g) in the untreated sludge. After 105 days of treatment by composting, we noted a total reduction of helminth eggs in the order of 97.5, 97.83, and 98.37% for mixtures M1, M2, and M3, respectively. The Ascaris spp. eggs were reduced by 98% for M1 and M3 treatments and by 97% for M 2 Treatment. Toxocara spp., Hookworm spp., Trichuris spp., Capillaria spp., and Shistosoma spp. eggs were totally eliminated (100% decrease) and the Taenia spp. was absent from the first stage of composting. These results confirm the effectiveness of both dehydrating and composting processes on the removal of helminth eggs.

The prevalence of parasites in ornamental fish from fish market in Medan

NASA Astrophysics Data System (ADS)

Dewi, R. R.; Desrita; Fadhilla, A.

2018-02-01

Parasites still become the major problem in ornamental fish as the fast grown of its trading in Indonesia. Parasites causes diseases in ornamental fish hence followed by death and reducing its appearence. In this study, the prevalence of parasites in 100 apparently healthy ornamental fishes namely Guppy (Poecilia reticulate) and Goldfish (Carrasius auratus) were determined. The method of this research used was survey in local fish market in Medan from March to May 2017 The aim of this study was to determine the parasite that infects aquarium fishes and find out its prevalence. For this purpose, ornamental fishes were examined for parasites from their skin, fin, gill and intestine using wet mount method under a light microscope. The survey result showed that parasites that infect Guppy and Goldfish were Monogenea (Dactylogyrus sp and Gyrodactylus sp) in their skin and gill, Protozoa (piscinodinium sp) in their gill and Nematoda (Capillaria sp) in abdominal cavity. Prevalence rate of parasites that attack Guppy in Medan is Dactylogyrus sp (8%), Gyrodactylus sp (14 %), Piscinodinium sp (6%) and Capillaria sp (8%). Then, prevalence rate of Capilaria sp that attack Goldfish is 4%. The conclusion of this work revealed that the prevalence rate of ectoparasite and endoparasites in ornamental fishes in Medan had the low rate as well as there was no pathological findings is observed. However, these parasites could be a harmful parasitic diseases in case there is the changes in aquarium environment and improper fish handling.

Studies on some fish parasites of public health importance in the southern area of Saudi Arabia.

PubMed

Khalil, Mokhtar Ibrahim; El-Shahawy, Ismail Saad; Abdelkader, Hussein Saad

2014-01-01

The present study was the first attempt to survey the diversity of fish zoonotic parasites in the southern region of Saudi Arabia, particularly the Najran area, from October 2012 to October 2013. Approximately 163 fish representing seven species (two of freshwater fish and five of marine fish) were examined for fish-borne trematode metacercariae using the compression technique, and for zoonotic nematode larvae. Adult flukes were obtained from cats experimentally infected with the metacercariae on day 25 post-infection The prevalence of each parasite species was recorded. The parasites found belonged to two taxa: Digenea (Heterophyes heterophyes and Haplorchis pumilio) in muscle tissue; and nematodes (larvae of Capillaria sp.) in the digestive tract. The morphological characteristics of the fish-borne trematode metacercariae and their experimentally obtained adults were described. This is the first report of these parasites in fish in Saudi Arabia. Moreover, Myripristis murdjan presented higher prevalence of Capillaria sp. infection (22.7%), while Haplorchis pumilio was the dominant metacercarial species (7.9%). Although the number of documented cases continues to increase, the overall risk of human infection is slight. The increasing exploitation of the marine environment by humans and the tendency to reduce cooking times when preparing seafood products both increase the chances of becoming infected with these parasites. Furthermore, our results indicate that certain fish production systems are at risk of presenting fish zoonotic parasites, and that control approaches will benefit from understanding these risk factors.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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 available to test directly the influence of mutations and pharmacological strategies on the conformational equilibrium of monomeric αSyn. PMID:18198943

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 reinstated at generic level. Finally, a zoogeographical analysis of the flea beetle fauna in the Afrotropical region is provided. PMID:23378812

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

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.

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.

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.).

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 ± 0.3 mm (range, −0.2 to 1.2 mm) for the S-I, L-R, and A-P axes, respectively. The CT-SIM and synCT derived margins were <0.3 mm different. Conclusion: DRRs generated by synCT were in close agreement with CT-SIM. Planar and volumetric image registrations to synCT-derived targets were comparable with CT for phantom and patients. This validation is the next step toward MR-only planning for the brain.« less

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.

Trehalose does not improve neuronal survival on exposure to alpha-synuclein pre-formed fibrils.

PubMed

Redmann, Matthew; Wani, Willayat Y; Volpicelli-Daley, Laura; Darley-Usmar, Victor; Zhang, Jianhua

2017-04-01

Parkinson's disease is a debilitating neurodegenerative disorder that is pathologically characterized by intracellular inclusions comprised primarily of alpha-synuclein (αSyn) that can also be transmitted from neuron to neuron. Several lines of evidence suggest that these inclusions cause neurodegeneration. Thus exploring strategies to improve neuronal survival in neurons with αSyn aggregates is critical. Previously, exposure to αSyn pre-formed fibrils (PFFs) has been shown to induce aggregation of endogenous αSyn resulting in cell death that is exacerbated by either starvation or inhibition of mTOR by rapamycin, both of which are able to induce autophagy, an intracellular protein degradation pathway. Since mTOR inhibition may also inhibit protein synthesis and starvation itself can be detrimental to neuronal survival, we investigated the effects of autophagy induction on neurons with αSyn inclusions by a starvation and mTOR-independent autophagy induction mechanism. We exposed mouse primary cortical neurons to PFFs to induce inclusion formation in the presence and absence of the disaccharide trehalose, which has been proposed to induce autophagy and stimulate lysosomal biogenesis. As expected, we observed that on exposure to PFFs, there was increased abundance of pS129-αSyn aggregates and cell death. Trehalose alone increased LC3-II levels, consistent with increased autophagosome levels that remained elevated with PFF exposure. Interestingly, trehalose alone increased cell viability over a 14-d time course. Trehalose was also able to restore cell viability to control levels, but PFFs still exhibited toxic effects on the cells. These data provide essential information regarding effects of trehalose on αSyn accumulation and neuronal survival on exposure to PFF. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Antimüllerian hormone levels and cardiometabolic risk in young women with polycystic ovary syndrome.

PubMed

Feldman, Rebecca A; O'Neill, Kathleen; Butts, Samantha F; Dokras, Anuja

2017-01-01

To determine the association between antimüllerian hormone (AMH) levels and metabolic syndrome (MetSyn) in young women with polycystic ovary syndrome (PCOS). Cross-sectional study. Academic PCOS center. A total of 252 women aged 18-46 years with PCOS. None. Association of AMH with markers of cardiometabolic risk and MetSyn. The median AMH level was 5.1 ng/mL (interquartile range [IQR] 3.0-8.1), and prevalence of MetSyn was 23.8%. AMH levels positively correlated with total T, high-density lipoprotein (HDL) cholesterol, and SHBG and negatively correlated with fasting glucose, homeostasis-model assessment of insulin resistance, body mass index (BMI), and systolic and diastolic blood pressure. A single-unit decrease in AMH was associated with an 11% increase in odds of MetSyn (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.03-1.20); the strength of this association was maintained in the multivariate model (OR 1.09, 95% CI 1.01-1.18) adjusting for age and race. Subjects with AMH values in the lowest tertile were twice as likely as those in the highest tertile to have MetSyn (adjusted OR 2.1, 95% CI 1.01-4.3). Total T was not associated with MetSyn or its individual components. Our findings indicate that in young women with PCOS, low AMH levels predict a greater risk of MetSyn. The role of AMH, an established biomarker of ovarian reserve, in risk stratification of cardiometabolic risk in obese women with PCOS needs to be clarified in longitudinal studies and in the perimenopausal population. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

Characterization of cognitive deficits in rats overexpressing human alpha-synuclein in the ventral tegmental area and medial septum using recombinant adeno-associated viral vectors.

PubMed

Hall, Hélène; Jewett, Michael; Landeck, Natalie; Nilsson, Nathalie; Schagerlöf, Ulrika; Leanza, Giampiero; Kirik, Deniz

2013-01-01

Intraneuronal inclusions containing alpha-synuclein (a-syn) constitute one of the pathological hallmarks of Parkinson's disease (PD) and are accompanied by severe neurodegeneration of A9 dopaminergic neurons located in the substantia nigra. Although to a lesser extent, A10 dopaminergic neurons are also affected. Neurodegeneration of other neuronal populations, such as the cholinergic, serotonergic and noradrenergic cell groups, has also been documented in PD patients. Studies in human post-mortem PD brains and in rodent models suggest that deficits in cholinergic and dopaminergic systems may be associated with the cognitive impairment seen in this disease. Here, we investigated the consequences of targeted overexpression of a-syn in the mesocorticolimbic dopaminergic and septohippocampal cholinergic pathways. Rats were injected with recombinant adeno-associated viral vectors encoding for either human wild-type a-syn or green fluorescent protein (GFP) in the ventral tegmental area and the medial septum/vertical limb of the diagonal band of Broca, two regions rich in dopaminergic and cholinergic neurons, respectively. Histopathological analysis showed widespread insoluble a-syn positive inclusions in all major projections areas of the targeted nuclei, including the hippocampus, neocortex, nucleus accumbens and anteromedial striatum. In addition, the rats overexpressing human a-syn displayed an abnormal locomotor response to apomorphine injection and exhibited spatial learning and memory deficits in the Morris water maze task, in the absence of obvious spontaneous locomotor impairment. As losses in dopaminergic and cholinergic immunoreactivity in both the GFP and a-syn expressing animals were mild-to-moderate and did not differ from each other, the behavioral impairments seen in the a-syn overexpressing animals appear to be determined by the long term persisting neuropathology in the surviving neurons rather than by neurodegeneration.

Hsp31 Is a Stress Response Chaperone That Intervenes in the Protein Misfolding Process*

PubMed Central

Tsai, Chai-jui; Aslam, Kiran; Drendel, Holli M.; Asiago, Josephat M.; Goode, Kourtney M.; Paul, Lake N.; Rochet, Jean-Christophe; Hazbun, Tony R.

2015-01-01

The Saccharomyces cerevisiae heat shock protein Hsp31 is a stress-inducible homodimeric protein that is involved in diauxic shift reprogramming and has glyoxalase activity. We show that substoichiometric concentrations of Hsp31 can abrogate aggregation of a broad array of substrates in vitro. Hsp31 also modulates the aggregation of α-synuclein (αSyn), a target of the chaperone activity of human DJ-1, an Hsp31 homolog. We demonstrate that Hsp31 is able to suppress the in vitro fibrillization or aggregation of αSyn, citrate synthase and insulin. Chaperone activity was also observed in vivo because constitutive overexpression of Hsp31 reduced the incidence of αSyn cytoplasmic foci, and yeast cells were rescued from αSyn-generated proteotoxicity upon Hsp31 overexpression. Moreover, we showed that Hsp31 protein levels are increased by H2O2, in the diauxic phase of normal growth conditions, and in cells under αSyn-mediated proteotoxic stress. We show that Hsp31 chaperone activity and not the methylglyoxalase activity or the autophagy pathway drives the protective effects. We also demonstrate reduced aggregation of the Sup35 prion domain, PrD-Sup35, as visualized by fluorescent protein fusions. In addition, Hsp31 acts on its substrates prior to the formation of large aggregates because Hsp31 does not mutually localize with prion aggregates, and it prevents the formation of detectable in vitro αSyn fibrils. These studies establish that the protective role of Hsp31 against cellular stress is achieved by chaperone activity that intervenes early in the protein misfolding process and is effective on a wide spectrum of substrate proteins, including αSyn and prion proteins. PMID:26306045

'Prion-like' propagation of the synucleinopathy of M83 transgenic mice depends on the mouse genotype and type of inoculum.

PubMed

Sargent, Dorian; Verchère, Jérémy; Lazizzera, Corinne; Gaillard, Damien; Lakhdar, Latifa; Streichenberger, Nathalie; Morignat, Eric; Bétemps, Dominique; Baron, Thierry

2017-10-01

The M83 transgenic mouse is a model of human synucleinopathies that develops severe motor impairment correlated with accumulation of the pathological Ser129-phosphorylated α-synuclein (α-syn P ) in the brain and spinal cord. M83 disease can be accelerated by intracerebral inoculation of brain extracts from sick M83 mice. This has also recently been described using peripheral routes, injecting recombinant preformed α-syn fibrils into the muscle or the peritoneum. Here, we inoculated homozygous and/or hemizygous M83 neonates via the intraperitoneal and/or intracerebral routes with two different brain extracts: one from sick M83 mice inoculated with brain extract from other sick M83 mice, and the other derived from a human multiple system atrophy source passaged in M83 mice. Detection of α-syn P using ELISA and western blot confirmed the disease in mice. The distribution of α-syn P in the central nervous system was similar, independently of the inoculum or inoculation route, consistent with previous studies describing M83 disease. ELISA tests revealed higher levels of α-syn P in homozygous than in hemizygous sick M83 mice, at least after IC inoculation. Interestingly, the immunoreactivity of α-syn P detected by ELISA was significantly lower in M83 mice inoculated with the multiple system atrophy inoculum than in M83 mice inoculated with the M83 inoculum, at the first two passages. 'Prion-like' propagation of the synucleinopathy up to the clinical disease was accelerated by both intracerebral and intraperitoneal inoculations of brain extracts from sick mice. This acceleration, however, depends on the levels of α-syn expression by the mouse and the type of inoculum. © 2017 International Society for Neurochemistry.

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.

Phosphorylated α-Synuclein Accumulations and Lewy Body-like Pathology Distributed in Parkinson's Disease-Related Brain Areas of Aged Rhesus Monkeys Treated with MPTP.

PubMed

Huang, Baihui; Wu, Shihao; Wang, Zhengbo; Ge, Longjiao; Rizak, Joshua D; Wu, Jing; Li, Jiali; Xu, Lin; Lv, Longbao; Yin, Yong; Hu, Xintian; Li, Hao

2018-05-21

Phosphorylation of α-synuclein at serine 129 (P-Ser 129 α-syn) is involved in the pathogenesis of Parkinson's disease (PD) and Lewy body (LB) formation. However, there is no clear evidence indicates the quantitative relation of P-Ser 129 α-syn accumulation and dopaminergic cell loss, LBs pathology and the affected brain areas in PD monkeys. Here, pathological changes in the substantia nigra (SN) and PD-related brain areas were measured in aged monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) utilizing a modeling-recovery-remodeling strategy. Compared to age-matched controls, the MPTP-treated monkeys showed significantly reduced tyrosine hydroxylase (TH)-positive neurons and increased P-Ser 129 α-syn-positive aggregations in the SN. Double-labeling Immunofluorescence found some TH-positive neurons to be co-localized with P-Ser129 α-syn in the SN, suggesting the inverse correlation between P-Ser 129 α-syn aggregations and dopaminergic cell loss in the SN may represent an interactive association related to the progression of the PD symptoms in the model. P-Ser 129 α-syn aggregations or LB-like pathology was also found in the midbrain and the neocortex, specifically in the oculomotor nucleus (CN III), temporal cortex (TC), prefrontal cortex (PFC) and in cells surrounding the third ventricle. Notably, the occipital cortex (OC) was P-Ser 129 α-syn negative. The findings of LB-like pathologies, dopaminergic cell loss and the stability of the PD symptoms in this model suggest that the modeling-recovery-remodeling strategy in aged monkeys may provide a new platform for biomedical investigations into the pathogenesis of PD and potential therapeutic development. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

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

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.

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.

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

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.

(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.

Active inhibition of herpes simplex virus type 1-induced cell fusion

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

Bzik, D.J.; Person, S.; Read, G.S.

1982-01-01

Previous studies have demonstrated that syn mutant-infected cells fuse less well with nonsyncytial virus-infected cells than with uninfected cells, a phenomenon defined as function inhibition. The present study characterizes the kinetics as well as the requirements for expression of fusion inhibition. Initially, the capacity of sparse syn mutant-infected cells to fuse with uninfected surrounding cells was determined throughout infection. Of seven syn mutants examined, including representatives with alterations in two different viral genes that affect cell fusion, all showed an increase in fusion capacity up to 12 hr after infection and a decrease at later times. Fusion inhibition was examinedmore » in experiments employing sparse syn20-infected cells which had been incubated to a maximum fusion capacity; it was shown that surrounding cells infected with KOS, the parent of syn20, began to inhibit fusion by the syn20-infected cells at about 4 hr after infection, and that the maximum ability to inhibit fusion was attained at about 6 hr after infection. The metabolic blocking agents actinomycin D (RNA), cycloheximide (protein), 2-deoxyglucose, and tunicamycin (glycoslyation of glycoproteins) all showed the ability to inhibit the expression of fusion inhibition by KOS-infected cells if added shortly after infection. It is concluded that fusion inhibition is an active process that requires the synthesis of RNA, proteins, and glycoproteins. 17 references, 3 figures, 2 tables.« less

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.

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

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.

Curcumin Modulates α-Synuclein Aggregation and Toxicity

PubMed Central

2012-01-01

In human beings, Parkinson’s disease (PD) is associated with the oligomerization and amyloid formation of α-synuclein (α-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of α-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric α-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of α-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration of aggregation by curcumin may decrease the population of toxic oligomeric intermediates of α-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases. PMID:23509976

Cartilage Delamination Flap Mimicking a Torn Medial Meniscus

PubMed Central

Bin Abd Razak, Hamid Rahmatullah; Amit Kanta, Mitra

2016-01-01

We report a case of a chondral delamination lesion due to medial parapatellar plica friction syndrome involving the medial femoral condyle. This mimicked a torn medial meniscus in clinical and radiological presentation. Arthroscopy revealed a chondral delamination flap, which was debrided. Diagnosis of chondral lesions in the knee can be challenging. Clinical examination and MRI have good accuracy for diagnosis and should be used in tandem. Early diagnosis and treatment of chondral lesions are important to prevent progression to early osteoarthritis. PMID:28070434

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

Parasite prevalence, infection intensity and richness in an endangered population, the Atlantic-Gaspésie caribou.

PubMed

Turgeon, Geneviève; Kutz, Susan J; Lejeune, Manigandan; St-Laurent, Martin-Hugues; Pelletier, Fanie

2018-04-01

The Atlantic-Gaspésie caribou ( Rangifer tarandus caribou ) population is a small isolated relict herd considered endangered according to the Canadian Species at Risk Act (SARA). This population has low recruitment and survival rates but the potential role of parasites on individual fitness is unknown. In this context, we explored the parasite status of this population with the aim of 1) assessing the occurrence and intensity of parasite infections and the spatial, temporal and individual variations, 2) quantifying parasite richness and investigating factors such as sex and host body condition that may be associated with this variable and 3) evaluating the effects of parasite infections on survival in the Atlantic-Gaspésie caribou population. We examined fecal samples from 32 animals captured in 2013-2014 for eggs, oocysts and larvae of parasites and detected 7 parasite species: dorsal-spined larvae protostrongylids, presumably Parelaphostrongylus andersoni based on PCR identification of a subset, Nematodirus odocoilei and other unidentified Strongyles, Trichuris sp., Capillaria sp., Moniezia sp. and Eimeria sp. For each caribou, mean parasite species richness was 1.8 ± 1.1 (SD). Sex, body condition, year and capture location did not explain parasite prevalence, intensity of infection or richness except for intensity of infection of Capillaria sp. that was positively influenced by body condition. Parasites did not influence survival although mortality was higher for males than for females. We suggest that the relatively low and common gastrointestinal and protostrongylid parasite infections will not be a short-term threat leading to extinction.

Helminth Fauna Associated with Three Neotropical Bat Species (Chiroptera: Mormoopidae) in Veracruz, México.

PubMed

Clarke-Crespo, Emilio; de León, Gerardo Pérez-Ponce; Montiel-Ortega, Salvador; Rubio-Godoy, Miguel

2017-08-01

Bats are recognized as potential hosts of pathogens exploiting the food chain to reach them as definitive hosts. However, very little is known about their endoparasites, especially for Neotropical bats. In this study, we assessed the helminth fauna associated with 3 insectivorous bat species roosting in the same single hot cave in central Veracruz, México: Mormoops megalophylla, Pteronotus davyi, and Pteronotus personatus. During a period of 1 yr (April 2007-2008), 135 mormoopid bats in total were collected and examined for helminths. Six parasite species representing 3 types of intestinal helminths were found: 1 cestode Vampirolepis elongatus; 2 trematodes Maxbraunium tubiporum and Ochoterenatrema labda; and 3 nematodes Linustrongylus pteronoti, Molineidae gen. sp., and Capillaria sp. Overall, trematodes were the most abundant parasite group (72.4%), followed by nematodes (20.7%) and cestodes (6.9%). Species-accumulation curves suggest that the worms collected (n = 1,331) from these 6 parasite species comprise the helminth fauna associated with the 3 bat populations studied. The only species shared by the 3 bat species was Capillaria sp. Most (5/6) of the helminth species recorded use Lepidoptera and Diptera as intermediate hosts; therefore, diet is likely the main source of infection. Although insectivorous bats are considered dietary generalist species, the differences found in helminth diversity in these sympatric populations of closely related bat species, suggest that diet partitioning occurs in mormoopid bat communities. Helminths tend to exploit the food chain to reach their final hosts; therefore, studying these parasites can provide useful information to further understand the biology of bats.

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

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-NNE) at the roof of the Cycladic Eclogite Nappe, consistent with the Eocene extrusion of the high-pressure rocks in the Cyclades.

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-only planning and treatment for prostate radiotherapy.

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 Latreille, 1797 of Mydas Fabricius, 1794, n. syn. [Mydidae]; Nemestrina Latreille, 1809 of Nemestrinus Latreille, 1802, n. syn. [Nemestrinidae]; Pangonia Latreille, 1809 of Pangonius Latreille, 1802, n. syn. [Tabanidae]; Scatophaga Wiedemann, 1828 of Scathophaga Meigen, 1803, n. syn. [Scathophagidae]; Threneste Wiedemann, 1830 of Penthetria Meigen, 1803, n. syn. [Bibionidae].

Family-group names in Coleoptera (Insecta)

PubMed Central

Bouchard, Patrice; Bousquet, Yves; Davies, Anthony E.; Alonso-Zarazaga, Miguel A.; Lawrence, John F.; Lyal, Chris H. C.; Newton, Alfred F.; Reid, Chris A. M.; Schmitt, Michael; Ślipiński, S. Adam; Smith, Andrew B. T.

2011-01-01

Abstract We synthesize data on all known extant and fossil Coleoptera family-group names for the first time. A catalogue of 4887 family-group names (124 fossil, 4763 extant) based on 4707 distinct genera in Coleoptera is given. A total of 4492 names are available, 183 of which are permanently invalid because they are based on a preoccupied or a suppressed type genus. Names are listed in a classification framework. We recognize as valid 24 superfamilies, 211 families, 541 subfamilies, 1663 tribes and 740 subtribes. For each name, the original spelling, author, year of publication, page number, correct stem and type genus are included. The original spelling and availability of each name were checked from primary literature. A list of necessary changes due to Priority and Homonymy problems, and actions taken, is given. Current usage of names was conserved, whenever possible, to promote stability of the classification. New synonymies (family-group names followed by genus-group names): Agronomina Gistel, 1848 syn. nov. of Amarina Zimmermann, 1832 (Carabidae), Hylepnigalioini Gistel, 1856 syn. nov. of Melandryini Leach, 1815 (Melandryidae), Polycystophoridae Gistel, 1856 syn. nov. of Malachiinae Fleming, 1821 (Melyridae), Sclerasteinae Gistel, 1856 syn. nov. of Ptilininae Shuckard, 1839 (Ptinidae), Phloeonomini Ádám, 2001 syn. nov. of Omaliini MacLeay, 1825 (Staphylinidae), Sepedophilini Ádám, 2001 syn. nov. of Tachyporini MacLeay, 1825 (Staphylinidae), Phibalini Gistel, 1856 syn. nov. of Cteniopodini Solier, 1835 (Tenebrionidae); Agronoma Gistel 1848 (type species Carabus familiaris Duftschmid, 1812, designated herein) syn. nov. of Amara Bonelli, 1810 (Carabidae), Hylepnigalio Gistel, 1856 (type species Chrysomela caraboides Linnaeus, 1760, by monotypy) syn. nov. of Melandrya Fabricius, 1801 (Melandryidae), Polycystophorus Gistel, 1856 (type species Cantharis aeneus Linnaeus, 1758, designated herein) syn. nov. of Malachius Fabricius, 1775 (Melyridae), Sclerastes Gistel, 1856 (type species Ptilinus costatus Gyllenhal, 1827, designated herein) syn. nov. of Ptilinus Geoffroy, 1762 (Ptinidae), Paniscus Gistel, 1848 (type species Scarabaeus fasciatus Linnaeus, 1758, designated herein) syn. nov. of Trichius Fabricius, 1775 (Scarabaeidae), Phibalus Gistel, 1856 (type species Chrysomela pubescens Linnaeus, 1758, by monotypy) syn. nov. of Omophlus Dejean, 1834 (Tenebrionidae). The following new replacement name is proposed: Gompeliina Bouchard, 2011 nom. nov. for Olotelina Báguena Corella, 1948 (Aderidae). Reversal of Precedence (Article 23.9) is used to conserve usage of the following names (family-group names followed by genus-group names): Perigonini Horn, 1881 nom. protectum over Trechicini Bates, 1873 nom. oblitum (Carabidae), Anisodactylina Lacordaire, 1854 nom. protectum over Eurytrichina LeConte, 1848 nom. oblitum (Carabidae), Smicronychini Seidlitz, 1891 nom. protectum over Desmorini LeConte, 1876 nom. oblitum (Curculionidae), Bagoinae Thomson, 1859 nom. protectum over Lyprinae Gistel 1848 nom. oblitum (Curculionidae), Aterpina Lacordaire, 1863 nom. protectum over Heliomenina Gistel, 1848 nom. oblitum (Curculionidae), Naupactini Gistel, 1848 nom. protectum over Iphiini Schönherr, 1823 nom. oblitum (Curculionidae), Cleonini Schönherr, 1826 nom. protectum over Geomorini Schönherr, 1823 nom. oblitum (Curculionidae), Magdalidini Pascoe, 1870 nom. protectum over Scardamyctini Gistel, 1848 nom. oblitum (Curculionidae), Agrypninae/-ini Candèze, 1857 nom. protecta over Adelocerinae/-ini Gistel, 1848 nom. oblita and Pangaurinae/-ini Gistel, 1856 nom. oblita (Elateridae), Prosternini Gistel, 1856 nom. protectum over Diacanthini Gistel, 1848 nom. oblitum (Elateridae), Calopodinae Costa, 1852 nom. protectum over Sparedrinae Gistel, 1848 nom. oblitum (Oedemeridae), Adesmiini Lacordaire, 1859 nom. protectum over Macropodini Agassiz, 1846 nom. oblitum (Tenebrionidae), Bolitophagini Kirby, 1837 nom. protectum over Eledonini Billberg, 1820 nom. oblitum (Tenebrionidae), Throscidae Laporte, 1840 nom. protectum over Stereolidae Rafinesque, 1815 nom. oblitum (Throscidae) and Lophocaterini Crowson, 1964 over Lycoptini Casey, 1890 nom. oblitum (Trogossitidae); Monotoma Herbst, 1799 nom. protectum over Monotoma Panzer, 1792 nom. oblitum (Monotomidae); Pediacus Shuckard, 1839 nom. protectum over Biophloeus Dejean, 1835 nom. oblitum (Cucujidae), Pachypus Dejean, 1821 nom. protectum over Pachypus Billberg, 1820 nom. oblitum (Scarabaeidae), Sparrmannia Laporte, 1840 nom. protectum over Leocaeta Dejean, 1833 nom. oblitum and Cephalotrichia Hope, 1837 nom. oblitum (Scarabaeidae). PMID:21594053

Biophysics of α-Synuclein Membrane Interactions

PubMed Central

Pfefferkorn, Candace M.; Jiang, Zhiping; Lee, Jennifer C.

2011-01-01

Membrane proteins participate in nearly all cellular processes; however, because of experimental limitations, their characterization lags far behind that of soluble proteins. Peripheral membrane proteins are particularly challenging to study because of their inherent propensity to adopt multiple and/or transient conformations in solution and upon membrane association. In this review, we summarize useful biophysical techniques for the study of peripheral membrane proteins and their application in the characterization of the membrane interactions of the natively unfolded and Parkinson’s disease (PD) related protein, α-synuclein (α-syn). We give particular focus to studies that have led to the current understanding of membrane-bound α-syn structure and the elucidation of specific membrane properties that affect α-syn-membrane binding. Finally, we discuss biophysical evidence supporting a key role for membranes and α-syn in PD pathogenesis. PMID:21819966

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.

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

Alpha-Synuclein Produces Early Behavioral Alterations via Striatal Cholinergic Synaptic Dysfunction by Interacting With GluN2D N-Methyl-D-Aspartate Receptor Subunit.

PubMed

Tozzi, Alessandro; de Iure, Antonio; Bagetta, Vincenza; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Costa, Cinzia; Di Filippo, Massimiliano; Ghiglieri, Veronica; Latagliata, Emanuele Claudio; Wegrzynowicz, Michal; Decressac, Mickael; Giampà, Carmela; Dalley, Jeffrey W; Xia, Jing; Gardoni, Fabrizio; Mellone, Manuela; El-Agnaf, Omar Mukhtar; Ardah, Mustafa Taleb; Puglisi-Allegra, Stefano; Björklund, Anders; Spillantini, Maria Grazia; Picconi, Barbara; Calabresi, Paolo

2016-03-01

Advanced Parkinson's disease (PD) is characterized by massive degeneration of nigral dopaminergic neurons, dramatic motor and cognitive alterations, and presence of nigral Lewy bodies, whose main constituent is α-synuclein (α-syn). However, the synaptic mechanisms underlying behavioral and motor effects induced by early selective overexpression of nigral α-syn are still a matter of debate. We performed behavioral, molecular, and immunohistochemical analyses in two transgenic models of PD, mice transgenic for truncated human α-synuclein 1-120 and rats injected with the adeno-associated viral vector carrying wild-type human α-synuclein. We also investigated striatal synaptic plasticity by electrophysiological recordings from spiny projection neurons and cholinergic interneurons. We found that overexpression of truncated or wild-type human α-syn causes partial reduction of striatal dopamine levels and selectively blocks the induction of long-term potentiation in striatal cholinergic interneurons, producing early memory and motor alterations. These effects were dependent on α-syn modulation of the GluN2D-expressing N-methyl-D-aspartate receptors in cholinergic interneurons. Acute in vitro application of human α-syn oligomers mimicked the synaptic effects observed ex vivo in PD models. We suggest that striatal cholinergic dysfunction, induced by a direct interaction between α-syn and GluN2D-expressing N-methyl-D-aspartate receptors, represents a precocious biological marker of the disease. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Extracellular alpha-synuclein oligomers modulate synaptic transmission and impair LTP via NMDA-receptor activation.

PubMed

Diógenes, Maria José; Dias, Raquel B; Rombo, Diogo M; Vicente Miranda, Hugo; Maiolino, Francesca; Guerreiro, Patrícia; Näsström, Thomas; Franquelim, Henri G; Oliveira, Luís M A; Castanho, Miguel A R B; Lannfelt, Lars; Bergström, Joakim; Ingelsson, Martin; Quintas, Alexandre; Sebastião, Ana M; Lopes, Luísa V; Outeiro, Tiago Fleming

2012-08-22

Parkinson's disease (PD) is the most common representative of a group of disorders known as synucleinopathies, in which misfolding and aggregation of α-synuclein (a-syn) in various brain regions is the major pathological hallmark. Indeed, the motor symptoms in PD are caused by a heterogeneous degeneration of brain neurons not only in substantia nigra pars compacta but also in other extrastriatal areas of the brain. In addition to the well known motor dysfunction in PD patients, cognitive deficits and memory impairment are also an important part of the disorder, probably due to disruption of synaptic transmission and plasticity in extrastriatal areas, including the hippocampus. Here, we investigated the impact of a-syn aggregation on AMPA and NMDA receptor-mediated rat hippocampal (CA3-CA1) synaptic transmission and long-term potentiation (LTP), the neurophysiological basis for learning and memory. Our data show that prolonged exposure to a-syn oligomers, but not monomers or fibrils, increases basal synaptic transmission through NMDA receptor activation, triggering enhanced contribution of calcium-permeable AMPA receptors. Slices treated with a-syn oligomers were unable to respond with further potentiation to theta-burst stimulation, leading to impaired LTP. Prior delivery of a low-frequency train reinstated the ability to express LTP, implying that exposure to a-syn oligomers drives the increase of glutamatergic synaptic transmission, preventing further potentiation by physiological stimuli. Our novel findings provide mechanistic insight on how a-syn oligomers may trigger neuronal dysfunction and toxicity in PD and other synucleinopathies.

Synthesising acid mine drainage to maintain and exploit indigenous mining micro-algae and microbial assemblies for biotreatment investigations.

PubMed

Orandi, Sanaz; Lewis, David M

2013-02-01

The stringent regulations for discharging acid mine drainage (AMD) has led to increased attention on traditional or emerging treatment technologies to establish efficient and sustainable management for mine effluents. To assess new technologies, laboratory investigations on AMD treatment are necessary requiring a consistent supply of AMD with a stable composition, thus limiting environmental variability and uncertainty during controlled experiments. Additionally, biotreatment systems using live cells, particularly micro-algae, require appropriate nutrient availability. Synthetic AMD (Syn-AMD) meets these requirements. However, to date, most of the reported Syn-AMDs are composed of only a few selected heavy metals without considering the complexity of actual AMD. In this study, AMD was synthesised based on the typical AMD characteristics from a copper mine where biotreatment is being considered using indigenous AMD algal-microbes. Major cations (Ca, Na, Cu, Zn, Mg, Mn and Ni), trace metals (Al, Fe, Ag, Na, Co, Mo, Pb and Cr), essential nutrients (N, P and C) and high SO(4) were incorporated into the Syn-AMD. This paper presents the preparation of chemically complex Syn-AMD and the challenges associated with combining metal salts of varying solubility that is not restricted to one particular mine site. The general approach reported and the particular reagents used can produce alternative Syn-AMD with varying compositions. The successful growth of indigenous AMD algal-microbes in the Syn-AMD demonstrated its applicability as appropriate generic media for cultivation and maintenance of mining microorganisms for future biotreatment studies.

Enhanced motivation to alcohol in transgenic mice expressing human α-synuclein.

PubMed

Rotermund, Carola; Reolon, Gustavo K; Leixner, Sarah; Boden, Cindy; Bilbao, Ainhoa; Kahle, Philipp J

2017-11-01

α-Synuclein (αSYN) is the neuropathological hallmark protein of Parkinson's disease (PD) and related neurodegenerative disorders. Moreover, the gene encoding αSYN (SNCA) is a major genetic contributor to PD. Interestingly, independent genome-wide association studies also identified SNCA as the most important candidate gene for alcoholism. Furthermore, single-nucleotide-polymorphisms have been associated with alcohol-craving behavior and alcohol-craving patients showed augmented αSYN expression in blood. To investigate the effect of αSYN on the addictive properties of chronic alcohol use, we examined consumption, motivation, and seeking responses induced by environmental stimuli and relapse behavior in transgenic mice expressing the human mutant [A30P]αSYN throughout the brain. The primary reinforcing effects of alcohol under operant self-administration conditions were increased, while consumption and the alcohol deprivation effect were not altered in the transgenic mice. The same mice were subjected to immunohistochemical measurements of immediate-early gene inductions in brain regions involved in addiction-related behaviors. Acute ethanol injection enhanced immunostaining for the phosphorylated form of cAMP response element binding protein in both amygdala and nucleus accumbens of αSYN transgenic mice, while in wild-type mice no effect was visible. However, at the same time, levels of cFos remain unchanged in both genotypes. These results provide experimental confirmation of SNCA as a candidate gene for alcoholism in addition to its known link to PD. © 2017 International Society for Neurochemistry.

SU-F-303-12: Implementation of MR-Only Simulation for Brain Cancer: A Virtual Clinical Trial

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

Glide-Hurst, C; Zheng, W; Kim, J

2015-06-15

Purpose: To perform a retrospective virtual clinical trial using an MR-only workflow for a variety of brain cancer cases by incorporating novel imaging sequences, tissue segmentation using phase images, and an innovative synthetic CT (synCT) solution. Methods: Ten patients (16 lesions) were evaluated using a 1.0T MR-SIM including UTE-DIXON imaging (TE = 0.144/3.4/6.9ms). Bone-enhanced images were generated from DIXON-water/fat and inverted UTE. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating intersection and Dice similarity coefficients (DSC) using CT-SIM as ground truth. SynCTs were generated using voxel-based weighted summation incorporating T2, FLAIR, UTE1,more » and bone-enhanced images. Mean absolute error (MAE) characterized HU differences between synCT and CT-SIM. Dose was recalculated on synCTs; differences were quantified using planar gamma analysis (2%/2 mm dose difference/distance to agreement) at isocenter. Digitally reconstructed radiographs (DRRs) were compared. Results: On average, air maps intersected 80.8 ±5.5% (range: 71.8–88.8%) between MR-SIM and CT-SIM yielding DSCs of 0.78 ± 0.04 (range: 0.70–0.83). Whole-brain MAE between synCT and CT-SIM was 160.7±8.8 HU, with the largest uncertainty arising from bone (MAE = 423.3±33.2 HU). Gamma analysis revealed pass rates of 99.4 ± 0.04% between synCT and CT-SIM for the cohort. Dose volume histogram analysis revealed that synCT tended to yield slightly higher doses. Organs at risk such as the chiasm and optic nerves were most sensitive due to their proximities to air/bone interfaces. DRRs generated via synCT and CT-SIM were within clinical tolerances. Conclusion: Our approach for MR-only simulation for brain cancer treatment planning yielded clinically acceptable results relative to the CT-based benchmark. While slight dose differences were observed, reoptimization of treatment plans and improved image registration can address this limitation. Future work will incorporate automated registration between setup images (cone-beam CT and kilovoltage images) for synCT and CT-SIM. Submitting institution holds research agreements with Philips HealthCare, Best, Netherlands and Varian Medical Systems, Palo Alto, CA. Research partially sponsored via an Internal Mentored Research Grant.« less

A new species of Voria Robineau-Desvoidy (Diptera: Tachinidae) from Area de Conservación Guanacaste in northwestern Costa Rica.

PubMed

Fleming, A J; Wood, D Monty; Smith, M Alex; Dapkey, Tanya; Hallwachs, Winnie; Janzen, Daniel

2017-01-01

We describe a new species in the genus Voria Robineau-Desvoidy, 1830 (Diptera: Tachinidae: Voriini) from Area de Conservación Guanacaste (ACG) in northwestern Costa Rica. It was reared as part of an ongoing inventory of wild-caught caterpillars spanning a variety of moth and butterfly families (Lepidoptera). Our study provides a concise description of the new species using morphology, life history, molecular data, and photographic documentation. In addition to the new species, we provide a diagnosis of the genus as well as new data relating to host use. The following new species of Voria is described: Voria erasmocoronadoi Fleming & Wood sp. n. The following are proposed by Fleming & Wood as new synonyms of Voria : Xenoplagia Townsend, 1914 syn. n. , Hystricovoria Townsend, 1928 syn. n. , Afrovoria Curran, 1938 syn. n. , and Anavoria Mesnil, 1953 syn. n. , and Itavoria Townsend, 1931 syn. n. The following new combinations are proposed as a result of the new synonymies: Voria bakeri (Townsend, 1928), comb. n. and Voria setosa (Townsend, 1914), comb. n. The authors also propose Voria pollyclari (Rocha-e-Silva, Lopes & Della Lucia, 1999), comb. n. based on the morphology of the holotype.

Ice recrystallization kinetics in the presence of synthetic antifreeze glycoprotein analogues using the framework of LSW theory.

PubMed

Budke, C; Heggemann, C; Koch, M; Sewald, N; Koop, T

2009-03-05

The Ostwald ripening of polycrystalline ice in aqueous sucrose solutions was investigated experimentally. The kinetics of this ice recrystallization process was studied at temperatures between -6 and -10 degrees C and varying ice volume fractions. Using the theory of Lifshitz, Slyozov, and Wagner (LSW), the diffusion-limited rate constant for ice recrystallization was determined. Also, the effects of synthetic analogues of natural antifreeze glycoproteins (AFGP) were studied. These analogues synAFGPmi (i = 3-5) contained monosaccharide side groups instead of disaccharide side groups that occur in natural AFGP. In order to account for the inhibition effect of the synAFGPmi, we have modified classical LSW theory, allowing for the derivation of inhibition rate constants. It was found that the investigated synAFGPmi inhibit ice recrystallization at concentrations down to approximately 3 microg mL(-1) or, equivalently, approximately 1 micromol L(-1) for the largest synAFGPmi investigated: synAFGPm5. Hence, our new method is capable of quantitatively assessing the efficiency of very similar AFGP with a sensitivity that is at least 2 orders of magnitude larger than that typical for quantitative thermal hysteresis measurements.

α-Synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models.

PubMed

Mazzulli, Joseph R; Zunke, Friederike; Isacson, Ole; Studer, Lorenz; Krainc, Dimitri

2016-02-16

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the accumulation of protein aggregates comprised of α-synuclein (α-syn). A major barrier in treatment discovery for PD is the lack of identifiable therapeutic pathways capable of reducing aggregates in human neuronal model systems. Mutations in key components of protein trafficking and cellular degradation machinery represent important risk factors for PD; however, their precise role in disease progression and interaction with α-syn remains unclear. Here, we find that α-syn accumulation reduced lysosomal degradation capacity in human midbrain dopamine models of synucleinopathies through disrupting hydrolase trafficking. Accumulation of α-syn at the cell body resulted in aberrant association with cis-Golgi-tethering factor GM130 and disrupted the endoplasmic reticulum-Golgi localization of rab1a, a key mediator of vesicular transport. Overexpression of rab1a restored Golgi structure, improved hydrolase trafficking and activity, and reduced pathological α-syn in patient neurons. Our work suggests that enhancement of lysosomal hydrolase trafficking may prove beneficial in synucleinopathies and indicates that human midbrain disease models may be useful for identifying critical therapeutic pathways in PD and related disorders.

Synthetic biology: ensuring the greatest global value.

PubMed

Hollis, Aidan

2013-09-01

Synthetic biology (SynBio) has tremendous, transformative potential. Like other technologies, it can be used for good or ill. Currently, the structure of the allocation of potential benefits and risks is biased in favor of richer countries. The underlying problem is simple: most risks from SynBio are universal and affect both the rich and the poor with equal force; but benefits from SynBio can be expected to accrue chiefly to the rich. The risk/benefit balance is therefore skewed in a way that may lead to inefficient and unfair decisions. One potential solution is presented in this paper, using the principles that underlie the Health Impact Fund (HIF). The HIF is designed to reward companies based on assessed health impact, no matter where it occurs in the world, so that extending the life of a poor person is as profitable as extending the life of a rich person. This paper considers both the potential benefits and costs of SynBio; examines how the current global pharmaceutical industry is structured; introduces the HIF proposal; and finally explores how the principles underlying the HIF could be used productively with SynBio for global health.

The Interplay between Alpha-Synuclein Clearance and Spreading

PubMed Central

Lopes da Fonseca, Tomás; Villar-Piqué, Anna; Outeiro, Tiago Fleming

2015-01-01

Parkinson’s Disease (PD) is a complex neurodegenerative disorder classically characterized by movement impairment. Pathologically, the most striking features of PD are the loss of dopaminergic neurons and the presence of intraneuronal protein inclusions primarily composed of alpha-synuclein (α-syn) that are known as Lewy bodies and Lewy neurites in surviving neurons. Though the mechanisms underlying the progression of PD pathology are unclear, accumulating evidence suggests a prion-like spreading of α-syn pathology. The intracellular homeostasis of α-syn requires the proper degradation of the protein by three mechanisms: chaperone-mediated autophagy, macroautophagy and ubiquitin-proteasome. Impairment of these pathways might drive the system towards an alternative clearance mechanism that could involve its release from the cell. This increased release to the extracellular space could be the basis for α-syn propagation to different brain areas and, ultimately, for the spreading of pathology and disease progression. Here, we review the interplay between α-syn degradation pathways and its intercellular spreading. The understanding of this interplay is indispensable for obtaining a better knowledge of the molecular basis of PD and, consequently, for the design of novel avenues for therapeutic intervention. PMID:25874605

Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum.

PubMed

Luan, Yanan; Ren, Xiangpeng; Zheng, Wu; Zeng, Zhenhai; Guo, Yingzi; Hou, Zhidong; Guo, Wei; Chen, Xingjun; Li, Fei; Chen, Jiang-Fan

2018-01-01

Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils. We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. Importantly, chronic caffeine treatment did not affect autophagy processes in the normal striatum, but selectively reversed α-Syn-induced defects in macroautophagy (by enhancing microtubule-associated protein 1 light chain 3, and reducing the receptor protein sequestosome 1, SQSTM1/p62) and chaperone-mediated autophagy (CMA, by enhancing LAMP2A). These findings support that caffeine-a strongly protective environment factor as suggested by epidemiological evidence-may represent a novel pharmacological therapy for PD by targeting autophagy pathway.

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.

Gastrointestinal parasites of owls (Strigiformes) kept in captivity in the Southern region of Brazil.

PubMed

da Silva, Aleksandro S; Zanette, Régis A; Lara, Valéria M; Gressler, Luciane T; Carregaro, Adriano B; Santurio, Janio M; Monteiro, Silvia G

2009-01-01

The aim of this research was to study the gastrointestinal parasitism in 12 adult owls kept in captivity in the Southern region of Brazil. Cloacal contents of the species Rhinoptynx clamator, Tyto alba, Athene cunicularia, Megascops spp., and Bubo virginianus were evaluated. Feces and urine were collected and analyzed by the zinc sulfate centrifugal-flotation method and stained by the modified Ziehl-Neelsen technique. Eggs of Capillaria spp. and Strongylida, oocysts of Cryptosporidium spp., Eimeria spp., and Isospora spp. were observed. The birds showed no clinical signs, probably due to the mild nature of the infection.

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 containing site-specific cis–syn, trans–syn-I, (6-4), and Dewar pyrimi- done photoproducts of thymidylyl...Bypass of a site-specific cis–syn thymine dimer in a SV40 vector during in vitro replication by HeLa and XPV cell-free extracts, Biochemistry, 1998

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

A taxonomic monograph of the assassin bug genus Zelus Fabricius (Hemiptera: Reduviidae): 71 species based on 10,000 specimens

PubMed Central

Hart, Elwood R; Weirauch, Christiane

2016-01-01

Abstract The New World assassin bug genus Zelus Fabricius, 1803 (Insecta: Hemiptera: Heteroptera: Reduviidae: Harpactorinae: Harpactorini) is revised based on more than 10,000 specimens. Seventy-one species are recognized and twenty-four described as new: Zelus aithaleos sp. n., Zelus amblycephalus sp. n., Zelus antiguensis sp. n., Zelus auralanus sp. n., Zelus bahiaensis sp. n., Zelus banksi sp. n., Zelus casii sp. n., Zelus championi sp. n., Zelus cordazulus sp. n., Zelus fuliginatus sp. n., Zelus gilboventris sp. n., Zelus gracilipes sp. n., Zelus grandoculus sp. n., Zelus kartaboides sp. n., Zelus lewisi sp. n., Zelus panamensis sp. n., Zelus paracephalus sp. n., Zelus rosulentus sp. n., Zelus russulumus sp. n., Zelus spatulosus sp. n., Zelus truxali sp. n., Zelus umbraculoides sp. n., Zelus umbraculus sp. n., and Zelus xouthos sp. n. Five species, Zelus araneiformis Haviland, 1931, Zelus gradarius Bergroth, 1905, Zelus modestus (Stål, 1862), Zelus subfasciatus Stål, 1860 and Zelus vittaticeps Stål, 1866, are removed from Zelus and placed incertae sedis within Harpactorini. Nine new synonyms are recognized (senior synonym in parentheses): Zelus atripes Champion, 1898 syn. nov. (=Zelus conjungens [Stål, 1860]), Zelus dispar Fabricius, 1803 syn. nov. (=Zelus pedestris Fabricius, 1803), Zelus formosus Haviland, 1931 syn. nov. (=Zelus laticornis Herrich-Schaeffer, 1853), Zelus obscuridorsis (Stål, 1860) syn. nov. (=Zelus pedestris), Zelus pallidinervus Haviland, 1931 syn. nov. (=Zelus kartabensis Haviland, 1931), Zelus personatus Berg, 1879 syn. nov. (=Zelus versicolor Herrich-Schaeffer, 1848), Zelus trimaculatus Champion, 1898 syn. nov. (=Zelus means Fabricius, 1803), Zelus trimaculicollis (Stål, 1855) syn. nov. (=Zelus means), and Zelus tristis Haviland, 1931 syn. nov. (=Zelus laticornis). Zelus conjungens (Stål, 1860) stat. rev. Is resurrected from junior synonymy with zealous armillatus (Lepeletier & Seville, 1825). Zelus ambulans Stål, 1862 stat. rev. and Zelus cognatus (Costa, 1862) stat. rev. are resurrected from synonymy with Zelus exsanguis Stål, 1862. Iquitozelus Bérenger syn. nov. is synonymized with Zelus and its only species transferred to Zelus, hence resulting in a new combination, Zelus couturieri (Bérenger, 2003) comb. nov. Lectotypes, paralectotypes or neotypes are designated for a number of species. Habitus images, illustrations of male genitalia, distribution maps and measurements are provided for nearly all species. The three previously recognized subgenera of Zelus are found to be based upon superficial characters and these divisions do not reflect natural groupings. Using sets of characters, especially those of the male genitalia, eleven species groups are proposed. It is also hypothesized that Zelus is closely related to three other New World genera: Atopozelus Elkins, Ischnoclopius Stål and an undescribed genus "Hartzelus" [manuscript name]. Zelus is endemic to the New World, occurring naturally in the Caribbean and all but one of the continental countries, with introductions to Pacific islands, Europe and Chile. PMID:27651730

A taxonomic monograph of the assassin bug genus Zelus Fabricius (Hemiptera: Reduviidae): 71 species based on 10,000 specimens.

PubMed

Zhang, Guanyang; Hart, Elwood R; Weirauch, Christiane

2016-01-01

The New World assassin bug genus Zelus Fabricius, 1803 (Insecta: Hemiptera: Heteroptera: Reduviidae: Harpactorinae: Harpactorini) is revised based on more than 10,000 specimens. Seventy-one species are recognized and twenty-four described as new: Zelus aithaleos sp. n., Zelus amblycephalus sp. n., Zelus antiguensis sp. n., Zelus auralanus sp. n., Zelus bahiaensis sp. n., Zelus banksi sp. n., Zelus casii sp. n., Zelus championi sp. n., Zelus cordazulus sp. n., Zelus fuliginatus sp. n., Zelus gilboventris sp. n., Zelus gracilipes sp. n., Zelus grandoculus sp. n., Zelus kartaboides sp. n., Zelus lewisi sp. n., Zelus panamensis sp. n., Zelus paracephalus sp. n., Zelus rosulentus sp. n., Zelus russulumus sp. n., Zelus spatulosus sp. n., Zelus truxali sp. n., Zelus umbraculoides sp. n., Zelus umbraculus sp. n., and Zelus xouthos sp. n. Five species, Zelus araneiformis Haviland, 1931, Zelus gradarius Bergroth, 1905, Zelus modestus (Stål, 1862), Zelus subfasciatus Stål, 1860 and Zelus vittaticeps Stål, 1866, are removed from Zelus and placed incertae sedis within Harpactorini. Nine new synonyms are recognized (senior synonym in parentheses): Zelus atripes Champion, 1898 syn. nov. (=Zelus conjungens [Stål, 1860]), Zelus dispar Fabricius, 1803 syn. nov. (=Zelus pedestris Fabricius, 1803), Zelus formosus Haviland, 1931 syn. nov. (=Zelus laticornis Herrich-Schaeffer, 1853), Zelus obscuridorsis (Stål, 1860) syn. nov. (=Zelus pedestris), Zelus pallidinervus Haviland, 1931 syn. nov. (=Zelus kartabensis Haviland, 1931), Zelus personatus Berg, 1879 syn. nov. (=Zelus versicolor Herrich-Schaeffer, 1848), Zelus trimaculatus Champion, 1898 syn. nov. (=Zelus means Fabricius, 1803), Zelus trimaculicollis (Stål, 1855) syn. nov. (=Zelus means), and Zelus tristis Haviland, 1931 syn. nov. (=Zelus laticornis). Zelus conjungens (Stål, 1860) stat. rev. Is resurrected from junior synonymy with zealous armillatus (Lepeletier & Seville, 1825). Zelus ambulans Stål, 1862 stat. rev. and Zelus cognatus (Costa, 1862) stat. rev. are resurrected from synonymy with Zelus exsanguis Stål, 1862. Iquitozelus Bérenger syn. nov. is synonymized with Zelus and its only species transferred to Zelus, hence resulting in a new combination, Zelus couturieri (Bérenger, 2003) comb. nov. Lectotypes, paralectotypes or neotypes are designated for a number of species. Habitus images, illustrations of male genitalia, distribution maps and measurements are provided for nearly all species. The three previously recognized subgenera of Zelus are found to be based upon superficial characters and these divisions do not reflect natural groupings. Using sets of characters, especially those of the male genitalia, eleven species groups are proposed. It is also hypothesized that Zelus is closely related to three other New World genera: Atopozelus Elkins, Ischnoclopius Stål and an undescribed genus "Hartzelus" [manuscript name]. Zelus is endemic to the New World, occurring naturally in the Caribbean and all but one of the continental countries, with introductions to Pacific islands, Europe and Chile.

Reduction of Phosphorylated Synapsin I (Ser-553) Leads to Spatial Memory Impairment by Attenuating GABA Release after Microwave Exposure in Wistar Rats

PubMed Central

Qiao, Simo; Peng, Ruiyun; Yan, Haitao; Gao, Yabing; Wang, Changzhen; Wang, Shuiming; Zou, Yong; Xu, Xinping; Zhao, Li; Dong, Ji; Su, Zhentao; Feng, Xinxin; Wang, Lifeng; Hu, Xiangjun

2014-01-01

Background Abnormal release of neurotransmitters after microwave exposure can cause learning and memory deficits. This study investigated the mechanism of this effect by exploring the potential role of phosphorylated synapsin I (p-Syn I). Methods Wistar rats, rat hippocampal synaptosomes, and differentiated (neuronal) PC12 cells were exposed to microwave radiation for 5 min at a mean power density of 30 mW/cm2. Sham group rats, synaptosomes, and cells were otherwise identically treated and acted as controls for all of the following post-exposure analyses. Spatial learning and memory in rats was assessed using the Morris Water Maze (MWM) navigation task. The protein expression and presynaptic distribution of p-Syn I and neurotransmitter transporters were examined via western blotting and immunoelectron microscopy, respectively. Levels amino acid neurotransmitter release from rat hippocampal synaptosomes and PC12 cells were measured using high performance liquid chromatograph (HPLC) at 6 hours after exposure, with or without synapsin I silencing via shRNA transfection. Results In the rat experiments, there was a decrease in spatial memory performance after microwave exposure. The expression of p-Syn I (ser-553) was decreased at 3 days post-exposure and elevated at later time points. Vesicular GABA transporter (VGAT) was significantly elevated after exposure. The GABA release from synaptosomes was attenuated and p-Syn I (ser-553) and VGAT were both enriched in small clear synaptic vesicles, which abnormally assembled in the presynaptic terminal after exposure. In the PC12 cell experiments, the expression of p-Syn I (ser-553) and GABA release were both attenuated at 6 hours after exposure. Both microwave exposure and p-Syn I silencing reduced GABA release and maximal reduction was found for the combination of the two, indicating a synergetic effect. Conclusion p-Syn I (ser-553) was found to play a key role in the impaired GABA release and cognitive dysfunction that was induced by microwave exposure. PMID:24743689

Reduction of phosphorylated synapsin I (ser-553) leads to spatial memory impairment by attenuating GABA release after microwave exposure in Wistar rats.

PubMed

Qiao, Simo; Peng, Ruiyun; Yan, Haitao; Gao, Yabing; Wang, Changzhen; Wang, Shuiming; Zou, Yong; Xu, Xinping; Zhao, Li; Dong, Ji; Su, Zhentao; Feng, Xinxin; Wang, Lifeng; Hu, Xiangjun

2014-01-01

Abnormal release of neurotransmitters after microwave exposure can cause learning and memory deficits. This study investigated the mechanism of this effect by exploring the potential role of phosphorylated synapsin I (p-Syn I). Wistar rats, rat hippocampal synaptosomes, and differentiated (neuronal) PC12 cells were exposed to microwave radiation for 5 min at a mean power density of 30 mW/cm2. Sham group rats, synaptosomes, and cells were otherwise identically treated and acted as controls for all of the following post-exposure analyses. Spatial learning and memory in rats was assessed using the Morris Water Maze (MWM) navigation task. The protein expression and presynaptic distribution of p-Syn I and neurotransmitter transporters were examined via western blotting and immunoelectron microscopy, respectively. Levels amino acid neurotransmitter release from rat hippocampal synaptosomes and PC12 cells were measured using high performance liquid chromatograph (HPLC) at 6 hours after exposure, with or without synapsin I silencing via shRNA transfection. In the rat experiments, there was a decrease in spatial memory performance after microwave exposure. The expression of p-Syn I (ser-553) was decreased at 3 days post-exposure and elevated at later time points. Vesicular GABA transporter (VGAT) was significantly elevated after exposure. The GABA release from synaptosomes was attenuated and p-Syn I (ser-553) and VGAT were both enriched in small clear synaptic vesicles, which abnormally assembled in the presynaptic terminal after exposure. In the PC12 cell experiments, the expression of p-Syn I (ser-553) and GABA release were both attenuated at 6 hours after exposure. Both microwave exposure and p-Syn I silencing reduced GABA release and maximal reduction was found for the combination of the two, indicating a synergetic effect. p-Syn I (ser-553) was found to play a key role in the impaired GABA release and cognitive dysfunction that was induced by microwave exposure.

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 diverse array of cyclopropyl alcohol building blocks with high enantio- and diastereoselectivities. PMID:19954146

Biophysics of α-synuclein membrane interactions.

PubMed

Pfefferkorn, Candace M; Jiang, Zhiping; Lee, Jennifer C

2012-02-01

Membrane proteins participate in nearly all cellular processes; however, because of experimental limitations, their characterization lags far behind that of soluble proteins. Peripheral membrane proteins are particularly challenging to study because of their inherent propensity to adopt multiple and/or transient conformations in solution and upon membrane association. In this review, we summarize useful biophysical techniques for the study of peripheral membrane proteins and their application in the characterization of the membrane interactions of the natively unfolded and Parkinson's disease (PD) related protein, α-synuclein (α-syn). We give particular focus to studies that have led to the current understanding of membrane-bound α-syn structure and the elucidation of specific membrane properties that affect α-syn-membrane binding. Finally, we discuss biophysical evidence supporting a key role for membranes and α-syn in PD pathogenesis. This article is part of a Special Issue entitled: Membrane protein structure and function. Copyright © 2011. Published by Elsevier B.V.

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.

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

High-speed atomic force microscopy reveals structural dynamics of α -synuclein monomers and dimers

NASA Astrophysics Data System (ADS)

Zhang, Yuliang; Hashemi, Mohtadin; Lv, Zhengjian; Williams, Benfeard; Popov, Konstantin I.; Dokholyan, Nikolay V.; Lyubchenko, Yuri L.

2018-03-01

α-Synuclein (α-syn) is the major component of the intraneuronal inclusions called Lewy bodies, which are the pathological hallmark of Parkinson's disease. α-Syn is capable of self-assembly into many different species, such as soluble oligomers and fibrils. Even though attempts to resolve the structures of the protein have been made, detailed understanding about the structures and their relationship with the different aggregation steps is lacking, which is of interest to provide insights into the pathogenic mechanism of Parkinson's disease. Here we report the structural flexibility of α-syn monomers and dimers in an aqueous solution environment as probed by single-molecule time-lapse high-speed AFM. In addition, we present the molecular basis for the structural transitions using discrete molecular dynamics (DMD) simulations. α-Syn monomers assume a globular conformation, which is capable of forming tail-like protrusions over dozens of seconds. Importantly, a globular monomer can adopt fully extended conformations. Dimers, on the other hand, are less dynamic and show a dumbbell conformation that experiences morphological changes over time. DMD simulations revealed that the α-syn monomer consists of several tightly packed small helices. The tail-like protrusions are also helical with a small β-sheet, acting as a "hinge". Monomers within dimers have a large interfacial interaction area and are stabilized by interactions in the non-amyloid central (NAC) regions. Furthermore, the dimer NAC-region of each α-syn monomer forms a β-rich segment. Moreover, NAC-regions are located in the hydrophobic core of the dimer.

Vitamins K interact with N-terminus α-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and α-synuclein.

PubMed

da Silva, Fernanda Luna; Coelho Cerqueira, Eduardo; de Freitas, Mônica Santos; Gonçalves, Daniela Leão; Costa, Lilian Terezinha; Follmer, Cristian

2013-01-01

In the last decades, a series of compounds, including quinones and polyphenols, has been described as having anti-fibrillogenic action on α-synuclein (α-syn) whose aggregation is associated to the pathogenesis of Parkinson's disease (PD). Most of these molecules act as promiscuous anti-amyloidogenic agents, interacting with the diverse amyloidogenic proteins (mostly unfolded) through non-specific hydrophobic interactions. Herein we investigated the effect of the vitamins K (phylloquinone, menaquinone and menadione), which are 1,4-naphthoquinone (1,4-NQ) derivatives, on α-syn aggregation, comparing them with other anti-fibrillogenic molecules such as quinones, polyphenols and lipophilic vitamins. Vitamins K delayed α-syn fibrillization in substoichiometric concentrations, leading to the formation of short, sheared fibrils and amorphous aggregates, which are less prone to produce leakage of synthetic vesicles. In seeding conditions, menadione and 1,4-NQ significantly inhibited fibrils elongation, which could be explained by their ability to destabilize preformed fibrils of α-syn. Bidimensional NMR experiments indicate that a specific site at the N-terminal α-syn (Gly31/Lys32) is involved in the interaction with vitamins K, which is corroborated by previous studies suggesting that Lys is a key residue in the interaction with quinones. Together, our data suggest that 1,4-NQ, recently showed up by our group as a potential scaffold for designing new monoamine oxidase inhibitors, is also capable to modulate α-syn fibrillization in vitro. Copyright © 2012 Elsevier Ltd. All rights reserved.

On the photoisomerization of 5-hydroxytropolone: An ab initio and nuclear wave function study

NASA Astrophysics Data System (ADS)

Paz, Juan J.; Moreno, Miquel; Lluch, José M.

1997-10-01

In this paper we perform ab initio calculations for the stable conformations and the transition states for the isomerization processes in 5-hydroxytropolone in both the ground (S0) and first excited (S1) singlet electronic states. The Hartree-Fock self-consistent field (SCF) level and a complete active space SCF (CASSCF) level for S0 are considered, whereas the configuration interaction all single excitation method (CIS) and the CASSCF levels are used to deal with the S1 state. Energies are reevaluated at all levels through perturbation theory up to second order: Møller-Plesset for the Hartree-Fock and CIS methods, and the CASPT2 method for CAS results. The ab initio results are then used to perform different monodimensional fits to the potential energy surfaces in order to analyze the wave functions for the nuclear motions in both electronic states. Our best results predict that for the S0 state two stable conformers, syn and anti, can exist in thermal equilibrium. In accordance with experimental expectations the syn isomer is the most stable. As for the S1 state, and again in accord with experimental spectroscopical data, the order of stability reverses, the anti being the most stable. A more interesting result is that analysis of the nuclear wave functions shows an important syn-anti mixing in the S1 state that does not appear in S0. This result explains the appearance of syn-anti and anti-syn crossover transitions observed in the electronic spectra of 5-hydroxytropolone so that syn-anti reaction may take place through photoisomerization.

Registration of Azov meadow fescue

USDA-ARS?s Scientific Manuscript database

'Azov' meadow fescue [Schedonorus pratensis (Huds.) P. Beauv.; syn. Festuca pratensis Huds.; syn. Lolium pratense (Huds.) Darbysh.] is a synthetic population originating from 1000 parental genotypes. The parents of Azov were selected from ten Russian plant introductions, mostly originating from the...

Assessment of brain metabolite correlates of adeno-associated virus-mediated over-expression of human alpha-synuclein in cortical neurons by in vivo (1) H-MR spectroscopy at 9.4 T.

PubMed

Cuellar-Baena, Sandra; Landeck, Natalie; Sonnay, Sarah; Buck, Kerstin; Mlynarik, Vladimir; In 't Zandt, René; Kirik, Deniz

2016-06-01

In this study, we used proton-localized spectroscopy ((1) H-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild-type alpha-synuclein (α-syn) over-expression. Our goal was to find out if the increased α-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human α-syn formed the experimental group, whereas green fluorescent protein expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naïve controls. Data were acquired at 2, 4, and 8 month time points. Nineteen metabolites were quantified in the MR spectra using LCModel software. On the basis of 92 spectra, we evaluated any potential gender effect and found that lactate (Lac) levels were lower in males compared to females, while the opposite was observed for ascorbate (Asc). Next, we assessed the effect of age and found increased levels of GABA, Tau, and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lac levels (p = 0.005) were specifically lower in the α-syn group compared to the green fluorescent protein and control groups. In addition, Asc levels (p = 0.05) were increased in the vector-injected groups, whereas glucose levels remained unchanged. This study indicates that the metabolic switch between glucose-lactate could be detectable in vivo and might be modulated by Asc. No concomitant changes were found in markers of neuronal integrity (e.g., N-acetylaspartate) consistent with the fact that α-syn over-expression in cortical neurons did not result in neurodegeneration in this model. We acquired the neurochemical profile longitudinally in a rat model of human wild-type alpha-synuclein (α-syn) over-expression in cortical neurons. We found that Lactate levels were reduced in the α-syn group compared to the control groups and Ascorbate levels were increased in the vector-injected groups. No changes were found in markers of neuronal integrity consistent with the fact that α-syn over-expression did not result in frank neurodegeneration. © 2016 International Society for Neurochemistry.

Magnetic resonance imaging of the knee

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

Mink, J.H.; Reicher, M.A.; Crues, J.V.

1987-01-01

Introducing a comprehensive, practical guide to the use of magnetic resonance imaging (MRI) in detecting and evaluating knee disorders and planning arthroscopic surgery) This book integrates MRI findings with pertinent anatomy, physiology, and clinical signs to assist radiologists in selecting imaging protocols and interpreting scans. Detailed chapters focus on magnetic resonance imaging of the menisci and ligaments and evaluation of osteonecrosis, osteochondrosis, and osteochondritis. The authors demonstrate the potential of MRI for diagnosing various knee disorders such as arthritis, fractures, popliteal cysts, synovial disease, plicae, popliteal artery aneurysms, tumors, and bone marrow disorders.

Registration of 'Hidden Valley' meadow fescue

USDA-ARS?s Scientific Manuscript database

'Hidden Valley' (Reg. No. CV-xxxx, PI xxxxxx) meadow fescue [Schedonorus pratensis (Huds.) P. Beauv.; syn. Festuca pratensis Huds.; syn. Lolium pratense (Huds.) Darbysh.] is a synthetic population originating from 561 parental genotypes. The original germplasm is of unknown central or northern Europ...

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).

Alpha-Synuclein: From Early Synaptic Dysfunction to Neurodegeneration.

PubMed

Ghiglieri, Veronica; Calabrese, Valeria; Calabresi, Paolo

2018-01-01

Over the last two decades, many experimental and clinical studies have provided solid evidence that alpha-synuclein (α-syn), a small, natively unfolded protein, is closely related to Parkinson's disease (PD) pathology. To provide an overview on the different roles of this protein, here we propose a synopsis of seminal and recent studies that explored the many aspects of α-syn. Ranging from the physiological functions to its neurodegenerative potential, the relationship with the possible pathogenesis of PD will be discussed. Close attention will be paid on early cellular and molecular alterations associated with the presence of α-syn aggregates.

Taxonomic identity of the ghost ant, Tapinoma melanocephalum (Fabricius, 1793) (Formicidae: Dolichoderinae).

PubMed

Guerrero, Roberto J

2018-04-18

This paper revises the taxonomy of Tapinoma melanocephalum (Fabricius, 1793) as follows: T. melanocephalum = Tapinoma luffae (Kuriam, 1955) syn. nov., = Tapinoma melanocephalum coronatum Forel, 1908 syn. nov., = Tapinoma melanocephalum malesianum Forel, 1913 syn. nov. A neotype of Tapinoma melanocephalum (Fabricius, 1793) is designed here. Lectotypes of Tapinoma melanocephalum coronatum Forel, 1908 and T. melanocephalum malesianum Forel, 1913 are designated. Formica wallacei is proposed as a replacement name for Formica familiaris (= T. melanocephalum senior synonym). The worker, queen and male are redescribed and diagnosed. The morphological variability of populations is discussed. All castes are included in full color images.

Text Categorization Using Weight Adjusted k-Nearest Neighbor Classification

DTIC Science & Technology

1999-05-17

Experimental Results In this section, we compare kNN -mut which uses the weight vector obtained using mutual information as the fi- nal weight vector and...WAKNN against kNN , C4.5 [Qui93], RIPPER [Coh95], PEBLS [CS93], Rainbow [McC96], VSM [Low95] on several synthetic and real data sets. VSM is another k...obtained without this option. 3 C4.5 RIPPER PEBLS Rainbow kNN WAKNN Syn-1 100.0 100.0 100.0 100.0 77.3 100.0 Syn-2 67.5 69.5 62.0 50.0 66.0 68.8 Syn

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.

Molecular Details of α-Synuclein Membrane Association Revealed by Neutrons and Photons

PubMed Central

Jiang, Zhiping; Hess, Sara K.; Heinrich, Frank; Lee, Jennifer C.

2015-01-01

α-Synuclein (α-syn) is an abundant neuronal protein associated with Parkinson’s disease that is disordered in solution, but exists in equilibrium between a bent- and an elongated-helix on negatively charged membranes. Here, neutron reflectometry (NR) and fluorescence spectroscopy were employed to uncover molecular details of the interaction between α-syn and two anionic lipids, phosphatidic acid (PA) and phosphatidylserine (PS). Both NR and site-specific Trp measurements indicate that penetration depth of α-syn is similar for either PA- or PS-containing membranes (~9–11 Å from bilayer center) even though there is a preference for α-syn binding to PA. However, closer examination of the individual Trp quenching profiles by brominated lipids reveal differences into local membrane interactions especially at position 39 where conformational heterogeneity was observed. The data also indicate that while W94 penetrates the bilayer as deeply as W4, W94 resides in a more polar surrounding. Taken together, we suggest the N- and C-terminal regions near positions 4 and 94 are anchored to the membrane, while the putative linker spanning residue 39 samples multiple conformations, which are sensitive to the chemical nature of the membrane surface. This flexibility may enable α-syn to bind diverse biomembranes in vivo. PMID:25790164

Evidence of conformational exchange averaging in the thermal rotational spectrum of ethyl cyanoformate.

PubMed

True, Nancy S

2006-06-15

The Stark modulated low resolution microwave spectrum of ethyl cyanoformate between 21.5 and 24.0 GHz at 210, 300, and 358 K, which shows the J + 1 <-- J = 8 <-- 7 bands of three species, is compared to simulations based on electronic structure calculations at the MP2/6-311++G theory level. Calculations at this theory level reproduce the relative energies of the syn-anti and syn-gauche conformers, obtained in a previous study, and indicate that the barrier to conformer exchange is approximately 360 cm(-1) higher in energy than the syn-anti minimum. Simulated spectra of the eigenstates of the calculated O-ethyl torsional potential function reproduce the relative intensities and shapes of the lower and higher frequency bands which correspond to transitions of the syn-anti and syn-gauche conformers, respectively, but fail to reproduce the intense center band in the experimental spectra. A model incorporating exchange averaging reproduces the intensity of the center band and its temperature dependence. These simulations indicate that a large fraction of the thermal population at all three temperatures undergoes conformational exchange with an average energy specific rate constant, , of approximately 25 GHz. This model can explain anomalies present in rotational spectra of many other compounds composed of mixtures of conformers.

Multiple levels of redundant processes inhibit Caenorhabditis elegans vulval cell fates.

PubMed

Andersen, Erik C; Saffer, Adam M; Horvitz, H Robert

2008-08-01

Many mutations cause obvious abnormalities only when combined with other mutations. Such synthetic interactions can be the result of redundant gene functions. In Caenorhabditis elegans, the synthetic multivulva (synMuv) genes have been grouped into multiple classes that redundantly inhibit vulval cell fates. Animals with one or more mutations of the same class undergo wild-type vulval development, whereas animals with mutations of any two classes have a multivulva phenotype. By varying temperature and genetic background, we determined that mutations in most synMuv genes within a single synMuv class enhance each other. However, in a few cases no enhancement was observed. For example, mutations that affect an Mi2 homolog and a histone methyltransferase are of the same class and do not show enhancement. We suggest that such sets of genes function together in vivo and in at least some cases encode proteins that interact physically. The approach of genetic enhancement can be applied more broadly to identify potential protein complexes as well as redundant processes or pathways. Many synMuv genes are evolutionarily conserved, and the genetic relationships we have identified might define the functions not only of synMuv genes in C. elegans but also of their homologs in other organisms.

Multiple Levels of Redundant Processes Inhibit Caenorhabditis elegans Vulval Cell Fates

PubMed Central

Andersen, Erik C.; Saffer, Adam M.; Horvitz, H. Robert

2008-01-01

Many mutations cause obvious abnormalities only when combined with other mutations. Such synthetic interactions can be the result of redundant gene functions. In Caenorhabditis elegans, the synthetic multivulva (synMuv) genes have been grouped into multiple classes that redundantly inhibit vulval cell fates. Animals with one or more mutations of the same class undergo wild-type vulval development, whereas animals with mutations of any two classes have a multivulva phenotype. By varying temperature and genetic background, we determined that mutations in most synMuv genes within a single synMuv class enhance each other. However, in a few cases no enhancement was observed. For example, mutations that affect an Mi2 homolog and a histone methyltransferase are of the same class and do not show enhancement. We suggest that such sets of genes function together in vivo and in at least some cases encode proteins that interact physically. The approach of genetic enhancement can be applied more broadly to identify potential protein complexes as well as redundant processes or pathways. Many synMuv genes are evolutionarily conserved, and the genetic relationships we have identified might define the functions not only of synMuv genes in C. elegans but also of their homologs in other organisms. PMID:18689876

A new species of Voria Robineau-Desvoidy (Diptera: Tachinidae) from Area de Conservación Guanacaste in northwestern Costa Rica

PubMed Central

Wood, D. Monty; Smith, M. Alex; Dapkey, Tanya; Hallwachs, Winnie; Janzen, Daniel

2017-01-01

Abstract Background We describe a new species in the genus Voria Robineau-Desvoidy, 1830 (Diptera: Tachinidae: Voriini) from Area de Conservación Guanacaste (ACG) in northwestern Costa Rica. It was reared as part of an ongoing inventory of wild-caught caterpillars spanning a variety of moth and butterfly families (Lepidoptera). Our study provides a concise description of the new species using morphology, life history, molecular data, and photographic documentation. In addition to the new species, we provide a diagnosis of the genus as well as new data relating to host use. New information The following new species of Voria is described: Voria erasmocoronadoi Fleming & Wood sp. n. The following are proposed by Fleming & Wood as new synonyms of Voria: Xenoplagia Townsend, 1914 syn. n., Hystricovoria Townsend, 1928 syn. n., Afrovoria Curran, 1938 syn. n., and Anavoria Mesnil, 1953 syn. n., and Itavoria Townsend, 1931 syn. n. The following new combinations are proposed as a result of the new synonymies: Voria bakeri (Townsend, 1928), comb. n. and Voria setosa (Townsend, 1914), comb. n.The authors also propose Voria pollyclari (Rocha-e-Silva, Lopes & Della Lucia, 1999), comb. n. based on the morphology of the holotype. PMID:29391853

Prevalence of gastrointestinal helminth infections in free-range laying hens under mountain farming production conditions.

PubMed

Wuthijaree, K; Lambertz, C; Gauly, M

2017-12-01

1. A cross-sectional study was conducted from September 2015 to July 2016 in South Tyrol, Northern Italy to examine the prevalence of gastrointestinal helminths in free-range laying hens under mountain farming production conditions. 2. A total of 280 laying hens from 14 free-range mountain farms (4 organic, 10 conventional) were randomly collected at the end of the laying period. Faecal samples were taken to analyse faecal egg counts (FEC) and faecal oocyst counts (FOC). The gastrointestinal tracts were removed post mortem and examined for the presence of helminths. 3. In faeces, FEC values averaged 258 eggs per g of faeces, which were dominated by Ascaridia galli and Heterakis gallinarum. Mean FOC was 80 oocysts/g. In the gastrointestinal tract, at least one nematode species was found in 99.3% of the examined hens. H. gallinarum was the most prevalent nematode (95.7%), followed by Capillaria spp. (66.8%) and A. galli (63.6%). Thirty per cent of the chickens were infected with cestodes (tapeworms). Correlation coefficients between worm counts of H. gallinarum, Capillaria spp. and A. galli ranged from 0.41 to 0.51. 5. The helminth prevalence did not differ between conventional and organic farms, whereas total worm burden was higher in organic compared with conventional farms (318.9 vs. 112.0). Prevalence and infection intensity did not differ between farms that used anthelmintic treatments and those that did not. 6. In conclusion, free-range laying hens under the studied mountain farming conditions are at high risk of nematode infection, especially in organic systems. The vast majority of hens are subclinical infected with at least one helminth species.

Community-based primary prevention programs decrease the rate of metabolic syndrome among socioeconomically disadvantaged women.

PubMed

Gilstrap, Lauren Gray; Malhotra, Rajeev; Peltier-Saxe, Donna; Slicas, Donna; Pineda, Eliana; Culhane-Hermann, Catherine; Cook, Nakela; Fernandez-Golarz, Carina; Wood, Malissa

2013-04-01

Metabolic Syndrome (MetSyn) is one of the strongest predictors of type 2 diabetes (DM2) and cardiovascular disease (CVD). It is associated with a 4- to 10-fold increased risk of DM2 and a 2- to 3-fold increased risk of CVD. Low income and minority women have some of the highest rates of MetSyn. This study examines the effect of a unique, community based, primary prevention program on the rates of MetSyn and health habits. Sixty-four low income and minority women were enrolled in the HAPPY (Health Awareness and Primary Prevention in Your neighborhood) Heart Program in an eastern suburb of Boston. Over these 2 years, patients were evaluated by an interdisciplinary medical team: their primary physician, cardiologist, nutritionist, physical therapist, and health coach. The rate of MetSyn was measured at baseline, year 1, and year 2. Comparisons were made either using the paired t test for normally distributed variables or the Wilcoxon Sign test for non-normal variables. The rate of MetSyn fell from 64.7% at baseline to 34.9% at year 1 (p=0.01) and 28.2% at year 2 (p<0.001). This was driven by increases in high-density lipoprotein (HDL-C) (p<0.001) and decreases in blood pressure (p=0.05). Fasting blood glucose trended down, but the hemoglobin A1c (HbA1c) reached significance (decreasing from 6 to 5.8, p<0.01). Nutrition and exercise habits trended toward improvement. There were significant decreases in anxiety (p<0.001), depression (p=0.006) and stress (p=0.002). This lifestyle intervention program is effective at decreasing MetSyn in a socioeconomically disadvantaged, largely minority, female population. This program also decreases anxiety, stress, and depression among participants.

SYNTHESIS OF NOVEL CROWN ETHERS BEARING THE exo-cis-2,3-NORBORNYL GROUP AS POTENTIAL Na+ AND K+ EXTRACTANTS

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

Robeson, R.M.; Bonnesen, P.

2007-01-01

The synthesis of a series of novel dinorbornyl-16-crown-5 and dinorbornyl-18-crown-6 ethers that incorporate the exo-cis-2,3-norbornyl moiety within the macrocycle framework is described. The key starting material for the crown ethers, exo-cis-2,3-norbornanediol, was successfully prepared on a large (>30g) scale in 88% yield from norbornylene by osmium tetroxide-catalyzed hydroxylation. The syn and anti isomers of the dinorbornyl-16-crown-5 ether family were prepared using diethylene glycol with ring closure achieved using a methallyl linkage. The isomers cis-syn-cis and cis-anti-cis di-norbornano-15-methyleno-16-crown-5 (6A and 6B) could be separated using column chromatography, and a single crystal of the syn isomer 6A suitable for X-ray crystal structuremore » analysis was obtained, thereby confi rming the syn orientation. The syn and anti isomers of the dinorbornyl-18-crown-6 ether family were successfully prepared employing a different synthetic strategy, involving the potassium–templated cyclization of two bis-hydroxyethoxy-substituted exo-cis-2,3-norbornyl groups under high dilution conditions. Attempts to fully separate cis-syn-cis di-norbornano-18-crown-6 (10A) and cis-anti-cis di-norbornano-18-crown-6 (10B) from one another using column chromatography were unsuccessful. All intermediates and products were checked for purity using either thin layer chromatography or gas chromatography, and characterized by proton and carbon NMR. Crown ethers 6AB and 10AB are to our knowledge the fi rst crown ethers to incorporate the exo-cis-2,3-norbornyl moiety into the crown ring to be successfully synthesized and characterized.« less

The Protein Phosphatases of Synechocystis sp. Strain PCC 6803: Open Reading Frames sll1033 and sll1387 Encode Enzymes That Exhibit both Protein-Serine and Protein-Tyrosine Phosphatase Activity In Vitro.

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

Li, Ruiliang; Potters, M B.; Shi, Liang

2005-09-01

The open reading frames (ORFs) encoding two potential protein-serine/threonine phosphatases from the cyanobacterium Synechocystis sp. strain PCC 6803 were cloned and their protein products expressed in Escherichia coli cells. The product of ORF sll1033, SynPPM3, is a homologue of the PPM family of protein-serine/threonine phosphatases found in all eukaryotes as well as many members of the Bacteria. Surprisingly, the recombinant protein phosphatase dephosphorylated phosphotyrosine- as well as phosphoserine-containing proteins in vitro. While kinetic analyses indicate that the enzyme was more efficient at dephosphorylating the latter, replacement of Asp(608) by asparagine enhanced activity toward a phosphotyrosine-containing protein fourfold. The product ofmore » ORF sll1387, SynPPP1, is the sole homolog of the PPP family of protein phosphatases encoded by the genome of Synechocystis sp. strain PCC 6803. Like many other bacterial PPPs, the enzyme dephosphorylated phosphoserine- and phosphotyrosine-containing proteins with comparable efficiencies. However, while previously described PPPs from prokaryotic organisms required the addition of exogenous metal ion cofactors, such as Mg(2+) or Mn(2+), for activity, recombinantly produced SynPPP1 displayed near-maximal activity in the absence of added metals. Inductively coupled plasma mass spectrometry indicated that recombinant SynPPP1 contained significant quantities, 0.32 to 0.44 mol/mole total, of Mg and Mn. In this respect, the cyanobacterial enzyme resembled eukaryotic members of the PPP family, which are metalloproteins. mRNA encoding SynPPP1 or SynPPM3 could be detected in cells grown under many, but not all, environmental conditions.« less

New synonymies and new records of Afrotropical and Madagascan Pentatominae (Hemiptera: Heteroptera: Pentatomidae).

PubMed

Kment, Petr; Jindra, Zdeněk; Rider, David A

2014-09-24

The following new synonymies within the family Pentatomidae, subfamily Pentatominae, are established: Aesula Stål, 1876 = Pseudacrosternum Day, 1965, syn. nov. (Nezarini), Aesula viridissima (Signoret, 1861) = Aesula signoretiana Kirkaldy, 1909, syn. nov. = Pseudacrosternum cachani Day, 1965, syn. nov. = Pseudacrosternum cachani var. scutellatum Day, 1965, syn. nov., and Andocides vittaticeps (Stål, 1858) = Andocides vittaticeps var. viridescens Schumacher, 1913, syn. nov. Afrania brachyptera (Schaum, 1853), stat. restit., is restored as the oldest available name for that species, with Afrania wahlbergi Stål, 1854, syn. restit., being its junior synonym. Lectotype of Pentatoma viridissima Signoret, 1861 is designated, and lectotype designation of Pseudolerida incerta (Schouteden, 1909) is commented. The following new or confirmed state records are provided: Cappaeini: Leridella kenyensis Jeannel, 1913 (Cameroon), Paralerida bolivari (Schouteden, 1904) (Republic of the Congo, Uganda), P. niokana Linnavuori, 1982 (Uganda), Tripanda (Tripanda) dispar Schouteden, 1964 (Cameroon, Ghana, Liberia), T. (T.) horacekorum Kment & Jindra, 2009 (Cameroon, Guinea), T. (T.) jurickorum Kment & Jindra, 2009 (Gabon, Ivory Coast), T. (T.) longiceps (Villiers, 1967) (Democratic Republic of the Congo, Gabon), T. (T.) signitenens (Distant, 1898) (Democratic Republic of the Congo, Mozambique), T. (Tenerva) decorata (Jensen-Haarup, 1937) (Kenya, Oman, Tanzania); Carpocorini: Andocides vittaticeps (Angola); Diploxyini: Acoloba lanceolata (Fabricius, 1803) (Angola, Central African Republic, Zambia, Zimbabwe); Eysarcorini: Pseudolerida bitalensis Schouteden, 1958 (Cameroon), Pseudolerida incerta (Equatorial Guinea: Bioko Island, Tanzania, Uganda); Myrocheini: Humria bimaculicollis Linnavuori, 1975 (Botswana, Democratic Republic of the Congo, Guinea, Kenya, Mozambique, Namibia, South Africa, Zambia, Zimbabwe); Strachiini: Afrania brachyptera (Schaum, 1853) (Botswana, Democratic Republic of the Congo; Tanzania: Tanganyika, Zanzibar; Uganda). Variability of Tripanda jurickorum, Pseudolerida incerta and Humria bimaculicollis is discussed.

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

Psychosocial Factors in the Relationship between Socioeconomic Status and Cardiometabolic Risk: the HCHS/SOL Sociocultural Ancillary Study.

PubMed

McCurley, Jessica L; Penedo, Frank; Roesch, Scott C; Isasi, Carmen R; Carnethon, Mercedes; Sotres-Alvarez, Daniela; Schneiderman, Neil; Gonzalez, Patricia; Chirinos, Diana A; Camacho, Alvaro; Teng, Yanping; Gallo, Linda C

2017-08-01

U.S. Hispanics/Latinos display a high prevalence of metabolic syndrome (MetSyn), a group of co-occurring cardiometabolic risk factors (abdominal obesity, impaired fasting glucose, dyslipidemia, elevated blood pressure) associated with higher cardiovascular disease and mortality risk. Low socioeconomic status (SES) is associated with higher risk for MetSyn in Hispanics/Latinos, and psychosocial factors may play a role in this relationship. This cross-sectional study examined psychosocial factors in the association of SES and MetSyn components in 4,996 Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study. MetSyn components were measured at the baseline examination. Participants completed interviews to determine psychosocial risks (e.g., depression) and resources (e.g., social support) within 9 months of baseline (< 4 months in 72.6% of participants). Confirmatory factor analysis (CFA) and structural equation modeling (SEM) were used to identify latent constructs and examine associations. Participant mean age was 41.7 years (SE = 0.4) and 62.7% were female. CFA identified single latent factors for SES and psychosocial indicators, and three factors for MetSyn [blood pressure, lipids, metabolic factors]. SEMs showed that lower SES was related to MetSyn factors indirectly through higher psychosocial risk/lower resources (Y-Bχ 2 (df = 420) = 4412.90, p < .05, RMSEA = .042, SRMR = .051). A statistically significant effect consistent with mediation was found from lower SES to higher metabolic risk (glucose/waist circumference) via psychosocial risk/resource variables (Mackinnon's 95% asymmetric CI = -0.13 to -0.02). SES is related to metabolic variables indirectly through psychosocial factors in U.S. Hispanics/Latinos of diverse ancestries.

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.

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

Deep tunneling in the unimolecular decay of CH 3CHOO Criegee intermediates to OH radical products

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

Fang, Yi; Liu, Fang; Barber, Victoria P.

Unimolecular decay of Criegee intermediates produced in alkene ozonolysis is known to be a significant source of OH radicals in the troposphere. In this work, unimolecular decay of the methyl-substituted Criegee intermediate, syn-CH 3CHOO, to OH products is shown to occur at energies significantly below the transition state barrier for a 1,4 hydrogen transfer that leads to these products [Y. Fang et al., J. Chem. Phys. 144, 061102 (2016)]. The rate of appearance of OH products arising from tunneling through the barrier is obtained through direct time-domain measurements following the vibrational activation of syn-CH 3CHOO. IR excitation of syn-CH 3CHOOmore » at energies nearly 2000 cm -1 below the barrier is achieved through combination bands involving CH stretch and another lower frequency mode, and the resultant OH products are detected by UV laser-induced fluorescence. The observed syn-CH 3CHOO combination bands in the 4100–4350 cm -1 region are identified by comparison with the computed IR absorption spectrum. The experimental decay rates are found to be ca. 106 s -1 in this deep tunneling regime, which is approximately 100-times slower than that in the vicinity of the barrier.The experimental results are consistent with statistical Rice-Ramsperger-Kassel-Marcus (RRKM) calculations of the microcanonical decay rates with tunneling through the barrier, and notable deviations may originate from the sparsity in the density of states for syn-CH 3CHOO at lower energies. Thermal unimolecular decay of syn-CH 3CHOO is predicted to have significant contribution from microcanonical rates at energies that are much below the barrier.« less

Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies.

PubMed

Mazzulli, Joseph R; Xu, You-Hai; Sun, Ying; Knight, Adam L; McLean, Pamela J; Caldwell, Guy A; Sidransky, Ellen; Grabowski, Gregory A; Krainc, Dimitri

2011-07-08

Parkinson's disease (PD), an adult neurodegenerative disorder, has been clinically linked to the lysosomal storage disorder Gaucher disease (GD), but the mechanistic connection is not known. Here, we show that functional loss of GD-linked glucocerebrosidase (GCase) in primary cultures or human iPS neurons compromises lysosomal protein degradation, causes accumulation of α-synuclein (α-syn), and results in neurotoxicity through aggregation-dependent mechanisms. Glucosylceramide (GlcCer), the GCase substrate, directly influenced amyloid formation of purified α-syn by stabilizing soluble oligomeric intermediates. We further demonstrate that α-syn inhibits the lysosomal activity of normal GCase in neurons and idiopathic PD brain, suggesting that GCase depletion contributes to the pathogenesis of sporadic synucleinopathies. These findings suggest that the bidirectional effect of α-syn and GCase forms a positive feedback loop that may lead to a self-propagating disease. Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies. Copyright © 2011 Elsevier Inc. All rights reserved.

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

R Vasquez-Del Carpio; T Silverstein; S Lone

Exposure of DNA to UV radiation causes covalent linkages between adjacent pyrimidines. The most common lesion found in DNA from these UV-induced linkages is the cis-syn cyclobutane pyrimidine dimer. Human DNA polymerase {Kappa} (Pol{Kappa}), a member of the Y-family of DNA polymerases, is unable to insert nucleotides opposite the 3'T of a cis-syn T-T dimer, but it can efficiently extend from a nucleotide inserted opposite the 3'T of the dimer by another DNA polymerase. We present here the structure of human Pol{Kappa} in the act of inserting a nucleotide opposite the 5'T of the cis-syn T-T dimer. The structure revealsmore » a constrained active-site cleft that is unable to accommodate the 3'T of a cis-syn T-T dimer but is remarkably well adapted to accommodate the 5'T via Watson-Crick base pairing, in accord with a proposed role for Pol{Kappa} in the extension reaction opposite from cyclobutane pyrimidine dimers in vivo.« less

Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology.

PubMed

Ngolab, Jennifer; Trinh, Ivy; Rockenstein, Edward; Mante, Michael; Florio, Jazmin; Trejo, Margarita; Masliah, Deborah; Adame, Anthony; Masliah, Eliezer; Rissman, Robert A

2017-06-09

Proteins implicated in neurodegenerative conditions such as Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) have been identified in bodily fluids encased in extracellular vesicles called exosomes. Whether exosomes found in DLB patients can transmit pathology is not clear. In this study, exosomes were successfully harvested through ultracentrifugation from brain tissue from DLB and AD patients as well as non-diseased brain tissue. Exosomes extracted from brains diagnosed with either AD or DLB contained aggregate-prone proteins. Furthermore, injection of brain-derived exosomes from DLB patients into the brains of wild type mice induced α-synuclein (α-syn) aggregation. As assessed through immunofluorescent double labeling, α-syn aggregation was observed in MAP2 + , Rab5 + neurons. Using a neuronal cell line, we also identified intracellular α-syn aggregation mediated by exosomes is dependent on recipient cell endocytosis. Together, these data suggest that exosomes from DLB patients are sufficient for seeding and propagating α-syn aggregation in vivo.

Comparison of alpha-synuclein immunoreactivity in the spinal cord between the adult and aged beagle dog

PubMed Central

Ahn, Ji-Hyeon; Choi, Jung-Hoon; Park, Joon-Ha; Yan, Bing-Chun; Kim, In-Hye; Lee, Jae-Chul; Lee, Dae-Hwan; Kim, Jin-Sang

2012-01-01

Alpha-synuclein (α-syn) is a presynaptic protein that is richly expressed in the central and peripheral nervous systems of mammals, and it is related to the pathogenesis of Parkinson's disease and other neurodegenerative disorders. In the present study, we compared the distribution of the immunoreactivity of α-syn and its related gliosis in the spinal cord of young adult (2-3 years) and aged (10-12 years) beagle dogs. We discovered that α-syn immunoreactivity was present in many neurons in the thoracic level of the aged spinal cord, however, its protein level was not distinct inform that of the adult spinal cord. In addition, ionized calcium-binding adapter molecule-1 (a marker for microglia) immunoreactivity, and not glial fibrillary acidic protein (a marker for astrocytes) immunoreactivity, was somewhat increased in the aged group compared to the adult group. These results indicate that α-syn immunoreactivity was not dramatically changed in the dog spinal cord during aging. PMID:23091516

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.

Bimane Derivatives as Fluorescent Probes for Biological Macromolecules.

DTIC Science & Technology

1985-12-01

Kosower and Kosower three brcmobimanes for fluorescent labeling of biological systems. The three *: bromobimanes,2 6 mBBr (1), bBBr (2) and q8Br (3...3 CH j)CH 3 CH3 28r BrCH2 CH2Br(CH 3 NCH 2 - H2Br Br- ! 2 3 mBBr bBBr q8Br syn-(BrCH2 ,CH3 )(CH 3 ,CH3)B syn-(BrCH2,CH3 )B syn-(BrCH2 ,CH3 )((CH3...soluble fluorescent deriva- tive, which also has an absorption spectrum different from that of the agent. (1) mBBr + RS- ----) mBSR + Br- (2) bBBr

β-asarone increases MEF2D and TH levels and reduces α-synuclein level in 6-OHDA-induced rats via regulating the HSP70/MAPK/MEF2D/Beclin-1 pathway: Chaperone-mediated autophagy activation, macroautophagy inhibition and HSP70 up-expression.

PubMed

Huang, Liping; Deng, Minzhen; He, Yuping; Lu, Shiyao; Liu, Shu; Fang, Yongqi

2016-10-15

Inactive myocyte enhancer factor 2D (MEF2D) and alpha-synuclein (α-syn) aggregation will cause neuronal death. MEF2D or α-syn degradation is also associated with macroautophagy, chaperone-mediated autophagy (CMA) and heat-shock protein 70 (HSP70). We found that β-asarone had positive effects on treating 6-hydroxydopamine (6-OHDA)-induced rats, but mechanisms of β-asarone affecting on MEF2D and α-syn via regulating the HSP70/MAPK/MEF2D/Beclin-1 pathway remain unclear. Unilateral 6-OHDA injection into the medial forebrain bundle was used to create PD rats, which were divided into four groups and administered for 30days: 6-OHDA model group, MEF2D inhibitor-treated group (SB203580, 0.5mg/kg, i.p.), MEF2D activator-treated group (LiCl, 100mg/kg, i.p.), β-asarone-treated group (15mg/kg, p.o.). Expressions of tyrosine hydroxylase (TH), α-syn, heat-shock cognate protein 70 (HSC70), lysosome-associated membrane protein type 2a (LAMP-2A), MEF2D, HSP70, Beclin-1, light chain 3B (LC3B) and p62 in the mesencephalon were measured after 30-day administration. α-syn, Beclin-1 and LC3B levels were higher in the 6-OHDA model group, while TH, MEF2D, HSC70, LAMP-2A, p62 levels were lower compared to the sham-operated group. Our results also showed thatβ-asarone treatment reduced protein and mRNA levels of α-syn, Beclin-1 and LC3B, but increased HSP70, TH, MEF2D, HSC70, LAMP-2A and p62 levels compared to the 6-OHDA model group. Additionally, certain correlations among α-syn, TH, Beclin-1, LC3B, p62, HSP70, LAMP-2A and MEF2D were also discovered in this study. These findings suggested that β-asarone treatment could increase MEF2D and TH as well as reduce α-syn to protect against 6-OHDA induced damage in PD rat mesencephalon via modulating the HSP70/MAPK/MEF2D/Beclin-1 pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Fibrillar α-Synuclein and Huntingtin Exon 1 Assemblies Are Toxic to the Cells

PubMed Central

Pieri, Laura; Madiona, Karine; Bousset, Luc; Melki, Ronald

2012-01-01

The aggregation of alpha-synuclein (α-syn) and huntingtin (htt) into fibrillar assemblies in nerve and glial cells is a molecular hallmark of Parkinson's and Huntington's diseases. Within the aggregation process, prefibrillar and fibrillar oligomeric species form. Prefibrillar assemblies rather than fibrils are nowadays considered cytotoxic. However, recent reports describing spreading of fibrillar assemblies from one cell to another, in cell cultures, animal models, and brains of grafted patients suggest a critical role for fibrillar assemblies in pathogenesis. Here we compare the cytotoxic effect of defined and comparable particle concentrations of on-assembly pathway oligomeric and fibrillar α-syn and Htt fragment corresponding to the first exon of the protein (HttEx1). We show that homogeneous populations of α-syn and HttEx1 fibrils, rather than their precursor on-assembly pathway oligomers, are highly toxic to cultured cells and induce apoptotic cell death. We document the reasons that make fibrils toxic. We show that α-syn and HttEx1 fibrils bind and permeabilize lipid vesicles. We also show that fibrils binding to the plasma membrane in cultured cells alter Ca2+ homeostasis. Overall, our data indicate that fibrillar α-syn and HttEx1, rather than their precursor oligomers, are highly cytotoxic, the toxicity being associated to their ability to bind and permeabilize the cell membranes. PMID:22735540

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.

Sawflies of Ethiopia (Hymenoptera: Argidae, Tenthredinidae).

PubMed

Koch, Frank; Pauly, Alain; Hora, Zewdu A; Boevé, Jean-Luc

2015-09-24

Sawflies were collected in Ethiopia during 2010-2013. Three species represent new records for the country: Arge deckerti Koch, 2005, Athalia excisa Koch, 2006 and Xenapates nigrifrons Koch, 2012. Arge flavifrons Mocsáry, 1909, syn. n. and A. transvaalensis Cameron, 1911, syn. n. are subjective synonyms of A. micheli (Buysson, 1900) that is re-described here. Athalia fumosa Gribodo, 1879 sp. rev. is recognized as a valid species and is removed from synonymy with A. scioensis Gribodo, 1879. Distega braunsi Enslin, 1911 syn. n. and D. brunniventris Enslin, 1913 syn. n. are subjective synonyms of D. montium Konow, 1907. Pseudoneacidiophora Koch, 1998 is a new junior synonym of Kivua Forsius, 1934 (syn. n.), resulting in the new combination Kivua pleuritica (comb. n.) for Athalia pleuritica Forsius, 1927. Kivua camerunensis nom. n. is proposed for P. bicolor Koch, 1998 (preoccupied in Kivua by K. bicolor (Pasteels, 1949) (Bicrista bicolor Pasteels)), the second species formerly included in Pseudoneacidiophora. The female of Distega abyssinica Pasteels, 1955 is described for the first time. An annotated and illustrated list including six distribution maps is given for Ethiopian sawflies. It is composed of 34 species belonging to the genus Arge (Argidae), and seven genera of Tenthredinidae: Athalia (Athaliinae), Kivua, Neacidiophora, Xenapates (Allantinae), Distega, Trisodontophyes (Blennocampinae), and Dulophanes (Selandriinae). Some ecological aspects of Athalia species are discussed, especially for the most abundantly collected A. vollenhoveni Gribodo, 1879.

High-performance liquid chromatographic assay for the determination of novel triazole antifungal agents in tissue. Application to tissue distribution studies.

PubMed

Khan, J K; Montaseri, H; Poglod, M; Bu, H Z; Daneshtalab, M; Micetich, R G

2000-08-01

A simple and rugged reversed-phase high-performance liquid chromatographic method with ultraviolet absorbance detection at 263 nm was developed and validated for the analysis of novel triazole antifungal agents SYN-2869 and its derivatives in tissues. The method involved homogenization with 0.01 M phosphate buffer (pH 7.8) for lung, brain and spleen tissues. The liver and kidneys were homogenized with acetonitrile:acetone (1:1). The plasma proteins were precipitated with ice-cold acetonitrile and supernatent was evaporated to dryness. The reconstituted samples were injected onto an HPLC system. SYN-2869 was separated from the matrix components on a symmetry C(18) column using a aqueous mobile phase of acetonitrile and water with a flow rate of 1 mL/min. A step gradient of 40-80% acetonitrile eluted SYN-2869 and the internal standard (SYN-2506). The linear range was 0.5-10 microgram/g (r(2) > 0.99). The limit of quantitation was 0.5 microgram/g. The inter-day precision and accuracy for SYN 2869 standard concentration were from 2.6 to 7.4% and from -1.56 to +3.29%, respectively. The method was applied to tissue samples collected from single intravenous administration to mice to evaluate the distribution of these novel antifungal agents to different tissues. Copyright 2000 John Wiley & Sons, Ltd.

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.

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

Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

PubMed

Chang, Joseph; Yung, Katherine C

2014-11-01

This case report is the first documentation of dysphonia and vocal fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia (HHT). Case report of a 40-year-old man with HHT presenting with 2 years of worsening hoarseness. Hoarseness corresponded with a period of anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold telangiectasias, and plica ventricular is suggestive of previous submucosal vocal fold hemorrhage and subsequent counterproductive compensation with ventricular phonation. Hereditary hemorrhagic telangiectasia may present as dysphonia with vocal fold telangiectasias and place patients at risk of vocal fold hemorrhage. © The Author(s) 2014.

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.

Introducing Synchrotrons Into the Classroom

ScienceCinema

Bloch, Ashley; Lanzirotti, Tony

2018-06-08

Brookhaven's Introducing Synchrotrons Into the Classroom (InSynC) program gives teachers and their students access to the National Synchrotron Light Source through a competitive proposal process. The first batch of InSynC participants included a group of students from Islip Middle School, who used the massive machine to study the effectiveness of different what filters.

General Urban Warfare Amphibious Logistics Applications. Volume 4. Operational Plans.

DTIC Science & Technology

1983-06-23

region. b. Enemy Forces (1) Enem Situation. Survivors and stragglers from the MRB (Rein) that originally defended SYN City are still present in the city in...requirements and priorities in this region. b. Enemy Forces (1) Enem Situation. Survivors and stragglers from the MRB (Rein) that originally defended SYN City

76 FR 3135 - Pesticide Experimental Use Permit; Receipt of Extension Application;

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2009-0608; FRL-8855-3] Pesticide Experimental Use... (PIP) [Event 5307] Bacillus thuringiensis eCry3.1Ab protein and the genetic material necessary for its production (vector pSYN12274) in Event 5307 corn (SYN-[Oslash]53[Oslash]7-1) and combined and single trait...

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.

Insecticidal activity of two proteases against Spodoptera frugiperda larvae infected with recombinant baculoviruses

PubMed Central

2010-01-01

Background Baculovirus comprise the largest group of insect viruses most studied worldwide, mainly because they efficiently kill agricutural insect pests. In this study, two recombinant baculoviruses containing the ScathL gene from Sarcophaga peregrina (vSynScathL), and the Keratinase gene from the fungus Aspergillus fumigatus (vSynKerat), were constructed. and their insecticidal properties analysed against Spodoptera frugiperda larvae. Results Bioassays of third-instar and neonate S. frugiperda larvae with vSynScathL and vSynKerat showed a decrease in the time needed to kill the infected insects when compared to the wild type virus. We have also shown that both recombinants were able to increase phenoloxidase activity in the hemolymph of S. frugiperda larvae. The expression of proteases in infected larvae resulted in destruction of internal tissues late in infection, which could be the reason for the increased viral speed of kill. Conclusions Baculoviruses and their recombinant forms constitute viable alternatives to chemical insecticides. Recombinant baculoviruses containing protease genes can be added to the list of engineered baculoviruses with great potential to be used in integrated pest management programs. PMID:20587066

Five-year trends of selected halogenated flame retardants in the atmosphere of Northeast China.

PubMed

Li, Wen-Long; Liu, Li-Yan; Song, Wei-Wei; Zhang, Zi-Feng; Qiao, Li-Na; Ma, Wan-Li; Li, Yi-Fan

2016-01-01

This study collected 227 pairs of gas phase and particle phase air samples in a typical urban city of Northeast China from 2008 to 2013. Four alternative halogenated flame retardants for polybrominated diphenyl ethers (PBDEs) were analyzed, namely 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EHTBB), bis (2-ethylhexyl) tetrabromophthalate (BEHTBP), syn-dechlorane plus (syn-DP) and anti-dechlorane plus (anti-DP). The average concentrations for EHTBB and BEHTBP were 5.2 ± 20 and 30 ± 200 pg/m3, respectively, while for syn-DP and anti-DPwere 1.9±5.1 and 5.8±18 pg/m3, respectively. Generally, they were frequently detected in the particle phase, and the gas/particle partitioning suggested they were the maximum partition chemicals. The fractional abundance of EHTBB (fEHTBB) and syn-DP (fsyn)were comparablewith those in other studies. Strong local sources were identified based on the air parcel backward trajectories and the potential source contribution function. The concentrations of these chemicals were significantly increased during this sampling campaign, possibly suggesting their increasing usages from 2008 to 2013 in China.

Efficient Data Transfer Rate and Speed of Secured Ethernet Interface System.

PubMed

Ghanti, Shaila; Naik, G M

2016-01-01

Embedded systems are extensively used in home automation systems, small office systems, vehicle communication systems, and health service systems. The services provided by these systems are available on the Internet and these services need to be protected. Security features like IP filtering, UDP protection, or TCP protection need to be implemented depending on the specific application used by the device. Every device on the Internet must have network interface. This paper proposes the design of the embedded Secured Ethernet Interface System to protect the service available on the Internet against the SYN flood attack. In this experimental study, Secured Ethernet Interface System is customized to protect the web service against the SYN flood attack. Secured Ethernet Interface System is implemented on ALTERA Stratix IV FPGA as a system on chip and uses the modified SYN flood attack protection method. The experimental results using Secured Ethernet Interface System indicate increase in number of genuine clients getting service from the server, considerable improvement in the data transfer rate, and better response time during the SYN flood attack.

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

Efficient Data Transfer Rate and Speed of Secured Ethernet Interface System

PubMed Central

Ghanti, Shaila

2016-01-01

Embedded systems are extensively used in home automation systems, small office systems, vehicle communication systems, and health service systems. The services provided by these systems are available on the Internet and these services need to be protected. Security features like IP filtering, UDP protection, or TCP protection need to be implemented depending on the specific application used by the device. Every device on the Internet must have network interface. This paper proposes the design of the embedded Secured Ethernet Interface System to protect the service available on the Internet against the SYN flood attack. In this experimental study, Secured Ethernet Interface System is customized to protect the web service against the SYN flood attack. Secured Ethernet Interface System is implemented on ALTERA Stratix IV FPGA as a system on chip and uses the modified SYN flood attack protection method. The experimental results using Secured Ethernet Interface System indicate increase in number of genuine clients getting service from the server, considerable improvement in the data transfer rate, and better response time during the SYN flood attack. PMID:28116350

Review of subtribe Singilina Jeannel, 1949, of the Middle East and Central Asia (Coleoptera, Carabidae, Lebiini)

PubMed Central

Anichtchenko, Alexander

2011-01-01

Abstract Species of the genus Singilis Rambur, 1837 (Phloeozeteus Peyron, 1856, syn. n., Agatus Motschulsky, 1845, syn. n.), occurring in the Middle East and Central Asia are reviewed, with 24 species now recognized in the region, including ten species described as new: Singilis makarovi sp. n. (Tajikistan), Singilis jedlickai sp. n. (Afghanistan), Singilis kolesnichenkoi sp. n. (Iran), Singilis kabakovi sp. n. (Afghanistan, Iran), Singilis timuri sp. n. (Uzbekistan), Singilis klimenkoi sp. n. (Iran), Singilis saeedi sp. n. (Iran), Singilis felixi sp. n. (UAE), Singilis kryzhanovskii sp. n. (Iran, Turkmenistan), and Singilis timidus sp. n. (Iran); Singilis libani (Sahlberg, 1913) is recognized as a valid species; and Singilis solskyi nom. n. is proposed as a replacement name for Agatus bicolor (Solsky, 1874, not Rambur 1837), now placed in Singilis as junior homonym. New synonymies include: Singilis cingulatus (Gebler, 1843) = Singilis jakeschi Jedlička, 1967, syn. n.; Singilis mesopotamicus Pic, 1901 = Singilis apicalis Jedlička, 1956, syn. n. A key to species is provided. Habitus and aedeagal illustrations are provided for all species. Distributional data include many new country records. PMID:22291510

Crystal structure, matrix-isolation FTIR, and UV-induced conformational isomerization of 3-quinolinecarboxaldehyde.

PubMed

Kuş, Nihal; Henriques, Marta Sofia; Paixão, José António; Lapinski, Leszek; Fausto, Rui

2014-09-25

The crystal structure of 3-quinolinecarboxaldehyde (3QC) has been solved, and the compound has been shown to crystallize in the space group P21/c (monoclinic) with a = 6.306(4), b = 18.551(11), c = 6.999(4) Å, β = 106.111(13)°, and Z = 4. The crystals were found to exhibit pseudomerohedral twinning with a twin law corresponding to a two-fold rotation around the monoclinic (100) reciprocal lattice axis (or [4 0 1] in direct space). Individual molecules adopt the syn conformation in the crystal, with the oxygen atom of the aldehyde substituent directed toward the same side of the ring nitrogen atom. In the gas phase, the compound exists in two nearly isoenergetic conformers (syn and anti), which could be successfully trapped in solid argon at 10 K, and their infrared spectra are registered and interpreted. Upon in situ irradiation of matrix-isolated 3QC with UV light (λ > 315 nm), significant reduction of the population of the less stable anti conformer was observed, while that of the conformational ground state (syn conformer) increased, indicating occurrence of the anti → syn isomerization. Upon irradiation at higher energy (λ > 235 nm), the syn → anti reverse photoreaction was observed. Interpretation of the structural, spectroscopic, and photochemical experimental data received support from quantum chemical theoretical results obtained at both DFT/B3LYP (including TD-DFT investigation of excited states) and MP2 levels, using the 6-311++G(d,p) basis set.

Oral Exposure to Paraquat Triggers Earlier Expression of Phosphorylated α-Synuclein in the Enteric Nervous System of A53T Mutant Human α-Synuclein Transgenic Mice

PubMed Central

Naudet, Nicolas; Antier, Emilie; Gaillard, Damien; Morignat, Eric; Lakhdar, Latifa; Baron, Thierry; Bencsik, Anna

2017-01-01

Abstract The misfolded α-synuclein protein, phosphorylated at serine 129 (pSer129 α-syn), is the hallmark of Parkinson disease (PD). Detected also in the enteric nervous system (ENS), it supports the recent theory that PD could start in the gut, rather than the brain. In a previous study, using a transgenic mouse model of human synucleinopathies expressing the A53T mutant α-synuclein (TgM83), in which a neurodegenerative process associated with α-synuclein occurs spontaneously in the brain, we have shown earlier onset of pSer129 α-syn in the ENS. Here, we used this model to study the impact of paraquat (PQ) a neurotoxic herbicide incriminated in PD in agricultural workers) on the enteric pSer129 α-syn expression in young mice. Orally delivered in the drinking water at 10 mg/kg/day for 6–8 weeks, the impact of PQ was measured in a time-dependent manner on weight, locomotor abilities, pSer129 α-syn, and glial fibrillary acidic protein (GFAP) expression levels in the ENS. Remarkably, pSer129 α-syn was detected in ENS earlier under PQ oral exposure and enteric GFAP expression was also increased. These findings bring additional support to the theory that neurotoxic agents such as PQ initiate idiopathic PD after oral delivery. PMID:29040593

Oral Exposure to Paraquat Triggers Earlier Expression of Phosphorylated α-Synuclein in the Enteric Nervous System of A53T Mutant Human α-Synuclein Transgenic Mice.

PubMed

Naudet, Nicolas; Antier, Emilie; Gaillard, Damien; Morignat, Eric; Lakhdar, Latifa; Baron, Thierry; Bencsik, Anna

2017-12-01

The misfolded α-synuclein protein, phosphorylated at serine 129 (pSer129 α-syn), is the hallmark of Parkinson disease (PD). Detected also in the enteric nervous system (ENS), it supports the recent theory that PD could start in the gut, rather than the brain. In a previous study, using a transgenic mouse model of human synucleinopathies expressing the A53T mutant α-synuclein (TgM83), in which a neurodegenerative process associated with α-synuclein occurs spontaneously in the brain, we have shown earlier onset of pSer129 α-syn in the ENS. Here, we used this model to study the impact of paraquat (PQ) a neurotoxic herbicide incriminated in PD in agricultural workers) on the enteric pSer129 α-syn expression in young mice. Orally delivered in the drinking water at 10 mg/kg/day for 6-8 weeks, the impact of PQ was measured in a time-dependent manner on weight, locomotor abilities, pSer129 α-syn, and glial fibrillary acidic protein (GFAP) expression levels in the ENS. Remarkably, pSer129 α-syn was detected in ENS earlier under PQ oral exposure and enteric GFAP expression was also increased. These findings bring additional support to the theory that neurotoxic agents such as PQ initiate idiopathic PD after oral delivery. © 2017 American Association of Neuropathologists, Inc.

Rethinking risk assessment for emerging technology first-in-human trials.

PubMed

Genske, Anna; Engel-Glatter, Sabrina

2016-03-01

Recent progress in synthetic biology (SynBio) has enabled the development of novel therapeutic opportunities for the treatment of human disease. In the near future, first-in-human trials (FIH) will be indicated. FIH trials mark a key milestone in the translation of medical SynBio applications into clinical practice. Fostered by uncertainty of possible adverse events for trial participants, a variety of ethical concerns emerge with regards to SynBio FIH trials, including 'risk' minimization. These concerns are associated with any FIH trial, however, due to the novelty of the approach, they become more pronounced for medical applications of emerging technologies (emTech) like SynBio. To minimize potential harm for trial participants, scholars, guidelines, regulations and policy makers alike suggest using 'risk assessment' as evaluation tool for such trials. Conversely, in the context of emTech FIH trials, we believe it to be at least questionable to contextualize uncertainty of potential adverse events as 'risk' and apply traditional risk assessment methods. Hence, this issue needs to be discussed to enable alterations of the evaluation process before the translational phase of SynBio applications begins. In this paper, we will take the opportunity to start the debate and highlight how a misunderstanding of the concept of risk, and the possibilities and limitations of risk assessment, respectively, might impair decision-making by the relevant regulatory authorities and research ethics committees, and discuss possible solutions to tackle the issue.

Coeval emplacement and orogen-parallel transport of gold in oblique convergent orogens

NASA Astrophysics Data System (ADS)

Upton, Phaedra; Craw, Dave

2016-12-01

Varying amounts of gold mineralisation is occurring in all young and active collisional mountain belts. Concurrently, these syn-orogenic hydrothermal deposits are being eroded and transported to form placer deposits. Local extension occurs in convergent orogens, especially oblique orogens, and facilitates emplacement of syn-orogenic gold-bearing deposits with or without associated magmatism. Numerical modelling has shown that extension results from directional variations in movement rates along the rock transport trajectory during convergence, and is most pronounced for highly oblique convergence with strong crustal rheology. On-going uplift during orogenesis exposes gold deposits to erosion, transport, and localised placer concentration. Drainage patterns in variably oblique convergent orogenic belts typically have an orogen-parallel or sub-parallel component; the details of which varies with convergence obliquity and the vagaries of underlying geological controls. This leads to lateral transport of eroded syn-orogenic gold on a range of scales, up to > 100 km. The presence of inherited crustal blocks with contrasting rheology in oblique orogenic collision zones can cause perturbations in drainage patterns, but numerical modelling suggests that orogen-parallel drainage is still a persistent and robust feature. The presence of an inherited block of weak crust enhances the orogen-parallel drainage by imposition of localised subsidence zones elongated along a plate boundary. Evolution and reorientation of orogen-parallel drainage can sever links between gold placer deposits and their syn-orogenic sources. Many of these modelled features of syn-orogenic gold emplacement and varying amounts of orogen-parallel detrital gold transport can be recognised in the Miocene to Recent New Zealand oblique convergent orogen. These processes contribute little gold to major placer goldfields, which require more long-term recycling and placer gold concentration. Most eroded syn-orogenic gold becomes diluted by abundant lithic debris in rivers and sedimentary basins except where localised concentration occurs, especially on beaches.

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.

A dynamic structural model of expanded RNA CAG repeats: A refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations

PubMed Central

Yildirim, Ilyas; Park, Hajeung; Disney, Matthew D.; Schatz, George C.

2013-01-01

One class of functionally important RNA is repeating transcripts that cause disease through various mechanisms. For example, expanded r(CAG) repeats can cause Huntington’s and other disease through translation of toxic proteins. Herein, crystal structure of r[5ʹUUGGGC(CAG)3GUCC]2, a model of CAG expanded transcripts, refined to 1.65 Å resolution is disclosed that show both anti-anti and syn-anti orientations for 1×1 nucleotide AA internal loops. Molecular dynamics (MD) simulations using Amber force field in explicit solvent were run for over 500 ns on model systems r(5ʹGCGCAGCGC)2 (MS1) and r(5ʹCCGCAGCGG)2 (MS2). In these MD simulations, both anti-anti and syn-anti AA base pairs appear to be stable. While anti-anti AA base pairs were dynamic and sampled multiple anti-anti conformations, no syn-anti↔anti-anti transformations were observed. Umbrella sampling simulations were run on MS2, and a 2D free energy surface was created to extract transformation pathways. In addition, over 800 ns explicit solvent MD simulation was run on r[5ʹGGGC(CAG)3GUCC]2, which closely represents the refined crystal structure. One of the terminal AA base pairs (syn-anti conformation), transformed to anti-anti conformation. The pathway followed in this transformation was the one predicted by umbrella sampling simulations. Further analysis showed a binding pocket near AA base pairs in syn-anti conformations. Computational results combined with the refined crystal structure show that global minimum conformation of 1×1 nucleotide AA internal loops in r(CAG) repeats is anti-anti but can adopt syn-anti depending on the environment. These results are important to understand RNA dynamic-function relationships and develop small molecules that target RNA dynamic ensembles. PMID:23441937

Measurement of Hemoglobin Synthesis Rate in Vivo Using a Stable Isotope Method

PubMed Central

Hibbert, Jacqueline M.; Sutherland, George B.; Wright, Luther L.; Wolfe, Luke G.; Wolfe, Kimberly A.; Gao, Shi Ping; Gore, Dennis C.; Abd-Elfattah, Anwar S.

2015-01-01

We developed a method to measure hemoglobin synthesis rate (SynHb) in humans, assuming that free glycine in the red blood cell (RBC) represents free glycine in bone marrow for hemoglobin synthesis. The present rat study examines this assumption of the method and quantifies SynHb in rats. Sprague–Dawley rats (n = 9) were studied, [2-13C]glycine was intravenously infused over 24 h (2.5 mg kg−1 h−1), blood was drawn for glycine and heme isolation, and bone marrow was harvested for glycine isolation. Isotopic enrichments of glycine and heme were measured, fractional hemoglobin synthesis rate (fSynHb% day−1) was calculated, and from this a value for SynHb (mg g−1 day−1) was derived. Mean body weight was 446 ± 10 g (mean ± SE) and hemoglobin concentration was 14 ± 0.5 g dl−1. At 24 h, the mean isotopic enrichment, atom percentage excess (APE), of the RBC free glycine (1.56 ± 0.18 APE) was similar to the bone marrow (1.68 ± 0.15 APE). The rate of incorporation of 13C into heme increased over time from 0.0004 APE/h between 6 and 12 h, to 0.0014 APE/h between 12 and 18 h, and 0.0024 APE/h between 18 and 24 h. Consequently, fSynHb (1.19 ± 0.32, 2.92 ± 0.66, and 4.22 ± 0.56% day−1, respectively) and SynHb (0.11 ± 0.03, 0.28 ± 0.05, and 0.42 ± 0.05 mg g−1 day−1, respectively) showed similar patterns over the 24-h study period. We conclude that (1) enrichment of free glycine in the circulating RBC approximates enrichment of bone marrow free glycine for heme formation and (2) this pattern of hemoglobin synthesis rate is reflecting the characteristic release and gradual maturation of reticulocytes in the circulation. PMID:11262164

Effects of rituximab in connective tissue disorders related interstitial lung disease.

PubMed

Lepri, Gemma; Avouac, Jerome; Airò, Paolo; Anguita Santos, Francisco; Bellando-Randone, Silvia; Blagojevic, Jelena; Garcia Hernàndez, Francisco; Gonzalez Nieto, Jose Antonio; Guiducci, Serena; Jordan, Suzana; Limaye, Vidya; Maurer, Britta; Selva-O'Callaghan, Albert; Riccieri, Valeria; Distler, Oliver; Matucci-Cerinic, Marco; Allanore, Yannick

2016-01-01

Interstitial lung disease (ILD) is a key prognostic factor in connective tissue disorders (CTDs). The aim of our study was to assess the changes in pulmonary functional tests (PFTs) in various CTDs, including anti-synthetase syndrome (SYN), systemic sclerosis (SSc) and mixed connective tissue disorder (MCTD), following the use of rituximab therapy. A multicentre retrospective analysis of patients with ILD secondary to SYN (n=15), MCTD (n=6) and SSc (n=23). PFTs were performed at baseline and at 1 and 2 years of follow-up. The primary outcome was the change in forced vital capacity (FVC) at 1 year. In the SYN population, median FVC changed from 53.0% (42.0-90.0) at baseline to 51.4% (45.6-85.0) at 1 year and 63.0 (50-88) (p=0.6) at 2 years (p=0.14). In SSc, FVC changed from 81.0% (66.0-104.0) at baseline to 89.0% (65.0-113.0) at 1 year (p=0.1) and 74.5 (50-91) at 2 years (p=0.07). In the MCTD population, FVC changed from 64.5% (63.0-68.0) at baseline to 63.0% (59.0-71.0) at 1 year (p=0.6) and 61 (59-71) after 2 years (p=0.8). DLCO showed a trend for improvement in the SYN population (p=0.06 at 1 year and 0.2 at years) while changes remain non-significant in the SSc and MCTD patients. In SYN patients, the percentage of responders at 1 year for FVC (33.3%) was greater than in SSc (9.5%) (p=0.07) and MCTD (17%) (p=0.45). RTX showed a satisfactory safety profile. A trend of improvement of PFTs was observed in SYN patients although not reaching significance, while SSc and MCTD patients were stabilised.

The case for metamorphic base metal mineralization: pyrite chemical, Cu and S isotope data from the Cu-Zn deposit at Kupferberg in Bavaria, Germany

NASA Astrophysics Data System (ADS)

Höhn, S.; Frimmel, H. E.; Debaille, V.; Pašava, J.; Kuulmann, L.; Debouge, W.

2017-12-01

The stratiform Cu-Zn sulfide deposit at Kupferberg in Germany represents Bavaria's largest historic base metal producer. The deposit is hosted by Early Paleozoic volcano-sedimentary strata at the margin of a high-grade allochthonous metamorphic complex. The present paper reports on the first Cu and S isotope data as well as trace element analyses of pyrite from this unusual deposit. The new data point to syn-orogenic mineralization that was driven by metamorphic fluids during nappe emplacement. Primary Cu ore occurs as texturally late chalcopyrite within stratiform laminated pyrite in black shale in two different tectonostratigraphic units of very low and low metamorphic grade, respectively, that were juxtaposed during the Variscan orogeny. Trace element contents of different pyrite types suggest the presence of at least one hydrothermal pyrite generation (mean Co/Ni = 35), with the other pyrite types being syn-sedimentary/early diagenetic (mean Co/Ni = 3.7). Copper isotope analyses yielded a narrow δ65Cu range of -0.26 to 0.36‰ for all ore types suggesting a hypogene origin for the principal chalcopyrite mineralization. The ore lenses in the two different tectonostratigraphic units differ with regard to their δ34S values, but little difference exists between poorly and strongly mineralized domains within a given locality. A genetic model is proposed in which syn-sedimentary/early diagenetic pyrite with subordinate chalcopyrite and sphalerite formed in black shale beds in the two different stratigraphic units, followed by late-tectonic strata-internal, hydrothermal mobilization of Fe, Cu, and Zn during syn-orogenic thrusting, which concentrated especially Cu to ore grade. In agreement with this model, Cu distribution in stream sediments in this region shows distinct enrichments bound to the margin of the allochthonous complex. Thus, Kupferberg can be considered a rare example of a syn-orogenic Cu deposit with the Cu probably being derived from syn-sedimentary/early diagenetic pyrite contained in Early Paleozoic shale units.

Poster — Thur Eve — 64: Preliminary investigation of arc configurations for optimal sparing of normal tissue in hypofractionated stereotactic radiotherapy (HF-SRT) of multiple brain metastases using a 5mm interdigitating micro-multileaf collimator

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

Leavens, C; Wronski, M; Lee, YK

2014-08-15

Purpose: To evaluate normal tissue sparing in intra-cranial HF-SRT, comparing various arc configurations with the Synergy Beam Modulator (SynBM) and Agility linacs, the latter incorporating leaf interdigitation and backup jaws. Methods: Five patients with multiple brain metastases (BMs), (5 BMs (n=2), 3 BMs (n=3)) treated with HF-SRT using 25 Gy (n=2) or 30 Gy (n=3) in 5 fractions, were investigated. Clinical treatment plans used the SynBM. Each patient was retrospectively re-planned on Agility, employing three planning strategies: (A) one isocenter and dedicated arc for each BM; (B) a single isocenter, centrally placed with respect to BMs; (C) the isocenter andmore » arc configuration used in the SynBM plan, where closely spaced (<5cm) BMs used a dedicated isocenter and arcs. Agility plans were normalized for PTV coverage and heterogeneity. Results and Conclusion: Strategy A obtained the greatest improvements over the SynBM plan, where the maximum OAR dose, and mean dose to normal brain (averaged for all patients) were reduced by 55cGy and 25cGy, respectively. Strategy B was limited by having a single isocenter, hence less jaw shielding and increased MLC leakage. The maximum OAR dose was reduced by 13cGy, however mean dose to normal brain increased by 84cGy. Strategy C reduced the maximum OAR dose and mean dose to normal brain by 32cGy and 9cGy, respectively. The results from this study indicate that, for intra-cranial HF-SRT of multiple BMs, Agility plans are equal or better than SynBM plans. Further planning is needed to investigate dose sparing using Strategy A and the SynBM.« less

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 westward migration; structural type's transformation from effusive magma and polygonal faults to magmatic diapirs and gas chimney. This study has an enlightening significance of the recognition of structural characteristics in the northern continental margin of the South China Sea during the post-rift period.

Recurrent selection for increased seed germination in sand bluestem (Andropogon hallii)

USDA-ARS?s Scientific Manuscript database

Water is essential for plant growth and under field conditions is often inadequate for satisfactory seed germination and seedling growth. The objective of this research was to improve the seed germination of sand bluestem (Andropogon hallii Hack.) lines ‘AB-medium Syn-0’ and ‘CD-tall Syn-0’ at low ...

77 FR 26547 - Amendment/Extension of an Experimental Use Permit

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-04

...-incorporated protectant (PIP) [Event 5307] Bacillus thuringiensis eCry3.1Ab protein and the genetic material necessary for its production (vector pSYN12274) in Event 5307 corn (SYN-[Oslash]53[Oslash]7-1) and combined and single trait hybrids with one or more of the following additional PIPs: (1) [Bt11] Bacillus...

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.

Medial abrasion syndrome: a neglected cause of knee pain in middle and old age.

PubMed

Lyu, Shaw-Ruey; Lee, Ching-Chih; Hsu, Chia-Chen

2015-04-01

Knee pain is a prevailing health problem of middle and old age. Medial plica-related medial abrasion syndrome (MAS), although a well-known cause of knee pain in younger individuals, has rarely been investigated in older individuals. This prospective study was conducted to investigate the prevalence and clinical manifestations of this syndrome as a cause of knee pain in middle and old age. The outcomes of arthroscopic treatment for this syndrome were also evaluated.A total of 232 knees of 169 patients >40 years of age (41-82, median: 63 years old) suffering from chronic knee pain were analyzed. The clinical diagnosis, predisposing factors, presenting symptoms, and physical signs were investigated. The sensitivity and specificity of each parameter of the clinical presentation for the diagnosis of MAS were evaluated after confirmation by arthroscopy. For patients with MAS, the roentgenographic and arthroscopic manifestations were investigated, and arthroscopic medial release (AMR) was performed. The outcomes were evaluated by the changes in the pain domain of the Knee Society scoring system and by patient satisfaction. The prevalence of medial plica was 95%, and osteoarthritis (OA) was the most common clinical diagnosis. Symptoms of pain and crepitus in motion and local tenderness during physical examination were the most sensitive parameters for the diagnosis. A history of a single knee injury combined with local tenderness and a palpable band found during physical examination were the most specific parameters for the diagnosis. The majority of patients suffering from this syndrome were successfully treated using AMR, yielding a satisfaction rate of 85.5% after a minimum of 3 years.MAS is a common cause of knee pain in middle and old age and can be effectively treated by AMR. Its concomitance with OA warrants further investigation.

Serratospiculosis in Captive Peregrine Falcons (Falco peregrinus) in Switzerland.

PubMed

Veiga, Inês B; Schediwy, Marion; Hentrich, Brigitte; Frey, Caroline F; Marreros, Nelson; Stokar-Regenscheit, Nadine

2017-09-01

Infection with Serratospiculum species was identified in a captive peregrine falcon (Falco peregrinus) in Switzerland. Pathologic and parasitologic examination results revealed generalized severe granulomatous airsacculitis, with intralesional adults, larvae, and eggs of Serratospiculum species. Subsequently, an individual coprological analysis of the remaining 15 falcons (peregrine falcons and gyrfalcons [Falco rusticolus]) from the same owner was performed. Eggs of Serratospiculum species (4 birds) and Capillaria species (11 birds), and oocysts of Caryospora species (1 bird) were detected. Treatment with ivermection (2 mg/kg SC) was effective, as none of the falcons excreted Serratospiculum species eggs 10 days after one dose. To our knowledge, this is the first report of infection with Serratospiculum species in captive falcons in Europe.

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.

Black women with polycystic ovary syndrome (PCOS) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with PCOS [corrected].

PubMed

Hillman, Jennifer K; Johnson, Lauren N C; Limaye, Meghana; Feldman, Rebecca A; Sammel, Mary; Dokras, Anuja

2014-02-01

To determine the prevalence of metabolic syndrome (MetSyn) and Framingham cardiovascular disease (CVD) risk in white and black adolescents and adult women with polycystic ovary syndrome (PCOS) compared with controls. Retrospective cohort study. Center for PCOS. Subjects with PCOS with data on race and cardiometabolic risk (n = 519). Controls were age and race matched from the National Health and Nutrition Examination Survey (NHANES) population (1999-2006). None. MetSyn, coronary heart disease risk, and general CVD risk. Black adolescents and young adults with PCOS had an increased prevalence of MetSyn compared with their white counterparts (adolescents relative risk 2.65 [95% confidence interval 1.29-5.4], adults relative risk 1.44 [95% confidence interval 1.21-2.6]). In contrast, there was no difference in risk of MetSyn between black and white adolescents and adult women in the NHANES dataset. After controlling for age and body mass index, black women with PCOS had a significantly increased prevalence of low high-density lipoprotein and high glucose. The general CVD risk was significantly increased in black adults with PCOS. This is the first study to comprehensively demonstrate increased risk of MetSyn in both black adolescents and adult women with PCOS compared with white subjects with PCOS. This racial disparity was not present in the NHANES controls. Longitudinal studies are needed to assess the independent impact of PCOS and race on CVD risk in women. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

Rycyna, R.E.; Wallace, J.C.; Sharma, M.

Acetone-photosensitized UV irradiation of three thymine oligomers, d(TpT), d(TpTpT), and d(TpTpTpT), forms predominantly cis-syn cyclobutyl photodimers. C-18 reverse-phase high-performance liquid chromatography is used to purify the following positional isomers: d(TpT(p)T), d(T(p)TpT), d-(TpTpT(p)T), d(TpT(p)TpT), d(T(p)TpTpT), and d(T(p)TpT(p)T), where T(p)T represents the cis-syn photodimer. Conformational properties of the cis-syn dimers and adjacent thymine nucleotides have been investigated in solution by using /sup 1/H, /sup 13/C, and /sup 31/P NMR spectroscopy. These studies show that (1) the photodimer conformation in longer oligothymidylates is similar to that in the dinucleoside monophosphate and (2) the cis-syn dimer induces alterations to a greater degree on themore » 5' side than on the 3' side of the photodimer. Specifically, the photodimer distorts the exocyclic bonds epsilon (C3'-O3') in Tp- and ..gamma..(C5'-C4') in -pT(p)- on the 5' side and slightly alters the furanose equilibrium of the -pT nucleotide on the 3' side of the dimer.« less

Characteristic Evaluation of Synchronous Motors Using an Universal Drive System with a Real-Time Interface

NASA Astrophysics Data System (ADS)

Amano, Yoko; Ogasawara, Satoshi

In this paper, a new universal drive system of synchronous motors used Real-Time Interface (RTI) performs characteristic evaluation of Synchronous Reluctance (SynR) motors and Surface Permanent Magnet (SPM) synchronous motors. The RTI connects directly a simulation model with experimental equipment, and makes it possible to use the simulation model for an experiment. The RTI is very effective in the early detection of an actual problem and examination of solution technique. Moreover, it concentrates on examination of control algorithm, and efficient research and development are enabled. A measuring system of synchronous motors is built by the universal drive system. The examination of various synchronous motors is possible for the measurement system using the same control algorithm. Characteristic evaluation of a SynR motor and a SPM synchronous motor that are the same gap length and stator was performed using the measuring system. The measurement result shows experimentally that motor loss of the SynR motor is smaller rather than the SPM synchronous motor, at the time of high speed and low load operation. For example, the SynR motor is suitable to hybrid cars with the comparatively long time of low load and high-speed operation.

Structural Effects of Two Camelid Nanobodies Directed to Distinct C-Terminal Epitopes on α-Synuclein.

PubMed

El-Turk, Farah; Newby, Francisco N; De Genst, Erwin; Guilliams, Tim; Sprules, Tara; Mittermaier, Anthony; Dobson, Christopher M; Vendruscolo, Michele

2016-06-07

α-Synuclein is an intrinsically disordered protein whose aggregation is associated with Parkinson's disease and other related neurodegenerative disorders. Recently, two single-domain camelid antibodies (nanobodies) were shown to bind α-synuclein with high affinity. Herein, we investigated how these two nanobodies (NbSyn2 and NbSyn87), which are directed to two distinct epitopes within the C-terminal domain of α-synuclein, affect the conformational properties of this protein. Our results suggest that nanobody NbSyn2, which binds to the five C-terminal residues of α-synuclein (residues 136-140), does not disrupt the transient long-range interactions that generate a degree of compaction within the native structural ensemble of α-synuclein. In contrast, the data that we report indicate that NbSyn87, which targets a central region within the C-terminal domain (residues 118-128), has more substantial effects on the fluctuating secondary and tertiary structure of the protein. These results are consistent with the different effects that the two nanobodies have on the aggregation behavior of α-synuclein in vitro. Our findings thus provide new insights into the type of effects that nanobodies can have on the conformational ensemble of α-synuclein.

HP LT Variscan metamorphism in the Cubito-Moura schists (Ossa-Morena Zone, southern Iberia)

NASA Astrophysics Data System (ADS)

Booth-Rea, Guillermo; Simancas, José Fernando; Azor, Antonio; Azañón, José Miguel; González-Lodeiro, Francisco; Fonseca, Paulo

2006-12-01

Multi-equilibrium thermobarometry shows that low-grade metapelites (Cubito-Moura schists) from the Ossa-Morena Zone underwent HP-LT metamorphism from 340-370 °C at 1.0-0.9 GPa to 400-450 °C at 0.8-0.7 GPa. These HP-LT equilibriums were reached by parageneses including white K mica, chlorite and chloritoid, which define the earliest schistosity (S 1) in these rocks. The main foliation in the schists is a crenulation cleavage (S 2), which developed during decompression from 0.8-0.7 to 0.4-0.3 GPa at increasing temperatures from 400-450 °C to 440-465 °C. Fe 3+ in chlorite decreased greatly during prograde metamorphism from molar fractions of 0.4 determined in syn-S 1 chlorites down to 0.1 in syn-S 2 chlorites. These new data add to previous findings of eclogites in the Moura schists indicating that a pile of allochtonous rocks situated next to the Beja-Acebuches oceanic amphibolites underwent HP-LT metamorphism during the Variscan orogeny. To cite this article: G. Booth-Rea et al., C. R. Geoscience 338 (2006).

North Polar Radiative Flux Variability from 2002 Through 2014

NASA Technical Reports Server (NTRS)

Rutan, David; Rose, Fred; Doelling, David; Kato, Seiji; Smith, Bill, Jr.

2017-01-01

NASA's Clouds and the Earth's Radiant Energy System (CERES) project produces the SYN1Deg data product. SYN1deg provides global, 1deg gridded, hourly estimates of Top of Atmosphere (TOA) (CERES observations and calculations) and atmospheric and surface radiative flux (calculations). Examples of 12 year North Polar averages of some variables are shown to the right. Given recent interest in polar science we focus here on TOA and Surface validation of calculated irradiant fluxes. TOA upward longwave irradiance calculations match the CERES observations well both spatially and temporally with correlations remaining strong through PC 6. Compare SYN1Deg Calculations & Meteorological Teleconnections. TOA reflected shortwave irradiance calculations match the CERES observations well both spatially and temporally with correlations remaining string through PC 7. Comparing SYN1Deg calculations to teleconnection patterns requires expanding the area to 30N for EOF analyses. Correlating the Principal Components of various variables to teleconnection time series indicates which variable is most highly correlated with which teleconnection signal. The tables indicate the Pacific North American Oscillation is most correlated to the OLR EOF 1, and the North American Oscillation is correlated most closely to surface LW flux down EOF 1.

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).

Combination therapies - the next logical step for the treatment of synucleinopathies?

PubMed Central

Valera, E.; Masliah, E.

2015-01-01

Currently there are no disease-modifying alternatives for the treatment of most neurodegenerative disorders. The available therapies for diseases such as Parkinson’s disease (PD), PD dementia (PDD), Dementia with Lewy bodies (DLB) and Multiple system atrophy (MSA), in which the protein alpha-synuclein (α-syn) accumulates within neurons and glial cells with toxic consequences, are focused on managing the disease symptoms. However, utilizing strategic drug combinations and/or multi-target drugs might increase the treatment efficiency when compared to monotherapies. Synucleinopathies are complex disorders that progress through several stages, and toxic α-syn aggregates exhibit prion-like behavior spreading from cell to cell. Therefore, it follows that these neurodegenerative disorders might require equally complex therapeutic approaches in order to obtain significant and long-lasting results. Hypothetically, therapies aimed at reducing α-syn accumulation and cell-to-cell transfer, such as immunotherapy against α-syn, could be combined with agents that reduce neuroinflammation with potential synergistic outcomes. Here we review the current evidence supporting this type of approach, suggesting that such rational therapy combinations, together with the use of multi-target drugs, may hold promise as the next logical step for the treatment of synucleinopathies. PMID:26388203

Thylakoid potassium channel is required for efficient photosynthesis in cyanobacteria.

PubMed

Checchetto, Vanessa; Segalla, Anna; Allorent, Guillaume; La Rocca, Nicoletta; Leanza, Luigi; Giacometti, Giorgio Mario; Uozumi, Nobuyuki; Finazzi, Giovanni; Bergantino, Elisabetta; Szabò, Ildikò

2012-07-03

A potassium channel (SynK) of the cyanobacterium Synechocystis sp. PCC 6803, a photoheterotrophic model organism for the study of photosynthesis, has been recently identified and demonstrated to function as a potassium selective channel when expressed in a heterologous system and to be located predominantly to the thylakoid membrane in cyanobacteria. To study its physiological role, a SynK-less knockout mutant was generated and characterized. Fluorimetric experiments indicated that SynK-less cyanobacteria cannot build up a proton gradient as efficiently as WT organisms, suggesting that SynK might be involved in the regulation of the electric component of the proton motive force. Accordingly, measurements of flash-induced cytochrome b(6)f turnover and respiration pointed to a reduced generation of ΔpH and to an altered linear electron transport in mutant cells. The lack of the channel did not cause an altered membrane organization, but decreased growth and modified the photosystem II/photosystem I ratio at high light intensities because of enhanced photosensitivity. These data shed light on the function of a prokaryotic potassium channel and reports evidence, by means of a genetic approach, on the requirement of a thylakoid ion channel for optimal photosynthesis.

Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients.

PubMed

Mackawy, Amal M H; Badawi, Mohammed E H

2014-12-01

To date the published data concerning the possible interplay between vitamin D (VitD) and Vit D receptor (VDR) gene polymorphism with the immune/inflammatory mediators in type 2 diabetes mellitus (DM) is insufficient. Some of the immune non-classical actions of vitamin D may point to its role in the pathogenesis of type 2 DM through down-regulation of cytokines (IL-6). Although there is evidence to support a relationship among vitamin D status, chronic inflammation and insulin resistance, the underlying mechanism requires further exploration. We aimed to investigate the role of vitamin D in chronic inflammation and insulin resistance in type 2 DM. Moreover, to examine the association of VDR gene polymorphisms [VDR 2228570 C > T (FokI); VDR 1544410 A > G (BsmI)] with the components of metabolic syndrome (MetSyn) in type 2 diabetic Egyptian patients . A total of 190 subjects were enrolled in this study, 60 controls and 130 type 2 diabetic patients (Group II). Group II was subdivided into 63 patients without MetSyn (subgroup IIa) and 67 patients with MetSyn (subgroup IIb). Genetic analysis for VDR gene polymorphisms was done in all subjects. VitD and IL-6 plasma levels were estimated. The TT genotype for the VDR FokI was significantly more frequent in subgroup IIb than in subgroup IIa and controls (X (2) = 6.83, P = 0.03 and X (2) = 16.592, P = 0.000) respectively. The T allele was more frequent in the MetSyn group as compared to diabetics without MetSyn (p = 0.001), odds ratio (OR) and 95% CI for the T allele of C > T (FokI) = 2.30 (1.37-3.86). We did not detect any significant difference in VDR BsmI genotypes between patients and control groups (P = 0.947). FokI VDR was significantly associated with the lipid profile parameters, VitD and IL-6 plasma levels in subgroup IIa and associated with HOMA-IR, insulin, VitD, IL-6 levels, waist circumference (WC) and body mass index (BMI) in subgroup IIb while BsmI VDR variant was associated only with VitD values in both subgroups. The present study suggests an interaction between VDR polymorphisms and important components of MetSyn, VitD and pro-inflammatory cytokines (IL-6). FokI VDR polymorphisms may be linked to mild inflammation and insulin resistance and might represent a genetic determinant for developing MetSyn in type 2 diabetic Egyptian patients. The challenge is determining the mechanisms of VitD action for recommendation of VitD supplementation that reduces the risks of MetSyn, insulin resistance and progression to type 2 diabetes.

Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients

PubMed Central

Mackawy, Amal M.H.; Badawi, Mohammed E.H.

2014-01-01

Background To date the published data concerning the possible interplay between vitamin D (VitD) and Vit D receptor (VDR) gene polymorphism with the immune/inflammatory mediators in type 2 diabetes mellitus (DM) is insufficient. Some of the immune non-classical actions of vitamin D may point to its role in the pathogenesis of type 2 DM through down-regulation of cytokines (IL-6). Although there is evidence to support a relationship among vitamin D status, chronic inflammation and insulin resistance, the underlying mechanism requires further exploration. We aimed to investigate the role of vitamin D in chronic inflammation and insulin resistance in type 2 DM. Moreover, to examine the association of VDR gene polymorphisms [VDR 2228570 C > T (FokI); VDR 1544410 A > G (BsmI)] with the components of metabolic syndrome (MetSyn) in type 2 diabetic Egyptian patients . Subjects and methods A total of 190 subjects were enrolled in this study, 60 controls and 130 type 2 diabetic patients (Group II). Group II was subdivided into 63 patients without MetSyn (subgroup IIa) and 67 patients with MetSyn (subgroup IIb). Genetic analysis for VDR gene polymorphisms was done in all subjects. VitD and IL-6 plasma levels were estimated. Results The TT genotype for the VDR FokI was significantly more frequent in subgroup IIb than in subgroup IIa and controls (X2 = 6.83, P = 0.03 and X2 = 16.592, P = 0.000) respectively. The T allele was more frequent in the MetSyn group as compared to diabetics without MetSyn (p = 0.001), odds ratio (OR) and 95% CI for the T allele of C > T (FokI) = 2.30 (1.37–3.86). We did not detect any significant difference in VDR BsmI genotypes between patients and control groups (P = 0.947). FokI VDR was significantly associated with the lipid profile parameters, VitD and IL-6 plasma levels in subgroup IIa and associated with HOMA-IR, insulin, VitD, IL-6 levels, waist circumference (WC) and body mass index (BMI) in subgroup IIb while BsmI VDR variant was associated only with VitD values in both subgroups. Conclusion The present study suggests an interaction between VDR polymorphisms and important components of MetSyn, VitD and pro-inflammatory cytokines (IL-6). FokI VDR polymorphisms may be linked to mild inflammation and insulin resistance and might represent a genetic determinant for developing MetSyn in type 2 diabetic Egyptian patients. The challenge is determining the mechanisms of VitD action for recommendation of VitD supplementation that reduces the risks of MetSyn, insulin resistance and progression to type 2 diabetes. PMID:25606437

Host-Parasite Interactions and Population Dynamics of Rock Ptarmigan.

PubMed

Stenkewitz, Ute; Nielsen, Ólafur K; Skírnisson, Karl; Stefánsson, Gunnar

2016-01-01

Populations of rock ptarmigan (Lagopus muta) in Iceland fluctuate in multiannual cycles with peak numbers c. every 10 years. We studied the ptarmigan-parasite community and how parasites relate to ptarmigan age, body condition, and population density. We collected 632 ptarmigan in northeast Iceland in early October from 2006 to 2012; 630 (99.7%) were infected with at least one parasite species, 616 (98%) with ectoparasites, and 536 (85%) with endoparasites. We analysed indices for the combined parasite community (16 species) and known pathogenic parasites, two coccidian protozoans Eimeria muta and Eimeria rjupa, two nematodes Capillaria caudinflata and Trichostrongylus tenuis, one chewing louse Amyrsidea lagopi, and one skin mite Metamicrolichus islandicus. Juveniles overall had more ectoparasites than adults, but endoparasite levels were similar in both groups. Ptarmigan population density was associated with endoparasites, and in particular prevalence of the coccidian parasite Eimeria muta. Annual aggregation level of this eimerid fluctuated inversely with prevalence, with lows at prevalence peak and vice versa. Both prevalence and aggregation of E. muta tracked ptarmigan population density with a 1.5 year time lag. The time lag could be explained by the host specificity of this eimerid, host density dependent shedding of oocysts, and their persistence in the environment from one year to the next. Ptarmigan body condition was negatively associated with E. muta prevalence, an indication of their pathogenicity, and this eimerid was also positively associated with ptarmigan mortality and marginally inversely with fecundity. There were also significant associations between fecundity and chewing louse Amyrsidea lagopi prevalence (negative), excess juvenile mortality and nematode Capillaria caudinflata prevalence (positive), and adult mortality and skin mite Metamicrolichus islandicus prevalence (negative). Though this study is correlational, it provides strong evidence that E. muta through time-lag in prevalence with respect to host population size and by showing significant relations with host body condition, mortality, and fecundity could destabilize ptarmigan population dynamics in Iceland.

Three-Dimensional Structural and Hydrologic Evolution of Sant Corneli Anticline, a Fault-Cored Fold in the Central Spanish Pyrenees

NASA Astrophysics Data System (ADS)

Shackleton, J. R.; Cooke, M. L.

2005-12-01

The Sant Corneli Anticline is a well-exposed example of a fault-cored fold whose hydrologic evolution and structural development are directly linked. The E-W striking anticline is ~ 5 km wide with abrupt westerly plunge, and formed in response to thrusting associated with the upper Cretaceous to Miocene collision of Iberia with Europe. The fold's core of fractured carbonates contains a variety of west dipping normal faults with meter to decameter scale displacement and abundant calcite fill. This carbonate unit is capped by a marl unit with low angle, calcite filled normal faults. The marl unit is overlain by clastic syn-tectonic strata whose sedimentary architecture records limb rotation during the evolution of the fold. The syn-tectonic strata contain a variety of joint sets that record the stresses before, during, and possibly after fold growth. Faulting in the marl and calcite-filled joints in the syn-tectonic strata suggest that normal faults within the carbonate core of the fold eventually breached the overlying marl unit. This breach may have connected the joints of the syn-tectonic strata to the underlying carbonate reservoir and eliminated previous compartmentalization of fluids. Furthermore, breaching of the marl units probably enhanced joint formation in the overlying syn-tectonic strata. Future geochemical studies of calcite compositions in the three units will address this hypothesis. Preliminary mapping of joint sets in the syn-tectonic strata reveal a multistage history of jointing. Early bed-perpendicular joints healed by calcite strike NE-SW, parallel to normal faults in the underlying carbonates, and may be related to an early regional extensional event. Younger healed bed-perpendicular joints cross cut the NE-SW striking set, and are closer to N-S in strike: these joints are interpreted to represent the initial stages of folding. Decameter scale, bed perpendicular, unfilled fractures that are sub-parallel to strike probably represent small joints and faults that formed in response to outer arc extension during folding. Many filled, late stage joints strike sub-parallel to, and increase in frequency near, normal faults and transverse structures observed in the carbonate fold core. This suggests that faulting in the underlying carbonates and marls significantly affected the joint patterns in the syn-tectonic strata. Preliminary three-dimensional finite element restorations using Dynel have allowed us to test our hypotheses and constrain the timing of jointing and marl breach.

Antimycobacterial, antimicrobial activity, experimental (FT-IR, FT-Raman, NMR, UV-Vis, DSC) and DFT (transition state, chemical reactivity, NBO, NLO) studies on pyrrole-isonicotinyl hydrazine

NASA Astrophysics Data System (ADS)

Rawat, Poonam; Singh, R. N.; Ranjan, Alok; Ahmad, Sartaj; Saxena, Rajat

2017-05-01

As part of a study of pyrrole hydrazone, we have investigated quantum chemical calculations, molecular geometry, relative energy, vibrational properties and antimycobacterial/antimicrobial activity of pyrrole-2-carboxaldehyde isonicotinyl hydrazone (PCINH), by applying the density functional theory (DFT) and Hartree Fock (HF). Good reproduction of experimental values is obtained and with small percentage error in majority of the cases in comparison to theoretical result (DFT). The experimental FT-IR and Raman wavenumbers were compared with the respective theoretical values obtained from DFT calculations and found to agree well. In crystal structure studies the hydrated PCINH (syn-syn conformer) shows different conformation than from anhydrous form (syn-anti conformer). The rotational barrier between syn-syn and syn-anti conformers of PCINH is 12.7 kcal/mol in the gas phase. In this work, use of FT-IR, FT-Raman, 1H NMR, 13C NMR and UV-Vis spectroscopies has been made for full characterization of PCINH. A detailed interpretation of the vibrational spectrum was carried out with the aid of normal coordinate analysis using single scaling factor. Our results support the hydrogen bonding pattern proposed by reported crystalline structure. The calculated nature of electronic transitions within molecule found to be π → π*. The electronic descriptors study indicates that PCINH can be used as robust synthon for synthesis of new heterocyclic compounds. The first static hyperpolarizability (β0) of PCINH is calculated as 33.89 × 10- 30 esu, (gas phase); 68.79 × 10- 30 (CHCl3), esu; 76.76 × 10- 30 esu (CH2Cl2), 85.16 × 10- 30 esu (DMSO). The solvent induced effects on the first static hyperpolarizability were studied and found to increase as dielectric constants of the solvents increases. Investigated molecule shows better NLO value than Para nitroaniline (PNA). The compound PCINH shows good antifungal and antibacterial activity against Aspergillus niger and gram-positive bacteria Bacillus subtilis, respectively. The compound also shows good antituberculosis activity against Mycobacterium tuberculosis H37Rv using the microplate alamar blue assay (MABA).

A revision of the spider genus Selenops Latreille, 1819 (Arachnida, Araneae, Selenopidae) in North America, Central America and the Caribbean.

PubMed

Crews, Sarah C

2011-01-01

The spider genus Selenops Latreille, 1819 occurs in both the Old World and New World tropics and subtropics and contains nearly half of the species in the family Selenopidae Simon, 1897. In this paper the members of the genus Selenops found in North America, Central America, and on islands of the Caribbean are revised, excluding Cuban endemics. No taxonomic changes are currently made to the species from the southwestern United States. In total, 21 new species are described, including Selenops arikoksp. n., Selenops chamelasp. n., Selenops amonasp. n., Selenops bawekasp. n., Selenops bocacanadensissp. n., Selenops enriquillosp. n, Selenops ixchelsp. n., Selenops huetocatlsp. n., Selenops kalinagosp. n., Selenops oviedosp. n., Selenops morrosp. n., Selenops deniasp. n., Selenops duansp. n., Selenops malinalxochitlsp. n., Selenops oricuajosp. n., Selenops petenajtoysp. n., Selenops guerrerosp. n., Selenops makimakisp. n., Selenops souligasp. n., Selenops wilmotorumsp. n., and Selenops wilsonisp. n. Six species names were synonymized: Selenops lunatus Muma, 1953 syn. n. =Selenops candidus Muma, 1953; Selenops tehuacanus Muma 1953 syn. n., Selenops galapagoensis Banks, 1902 syn. n. and Selenops vagabundus Kraus, 1955 syn. n. = Selenops mexicanus Keyserling, 1880; Selenops santibanezi Valdez-Mondragón, 2010 syn. n. = Selenops nigromaculatus Keyserling, 1880; and Selenops salvadoranus Chamberlin, 1925 syn. n. = Selenops bifurcatus Banks, 1909. Lectotypes are designated for the following three species: Selenops marginalis F. O. Pickard-Cambridge, 1900 (♂), Selenops morosus Banks, 1898 (♂), and Selenops mexicanus Keyserling, 1880 (♀). The female neotype is designated for Selenops aissus Walckenaer, 1837. The males of Selenops bani Alayón-García, 1992 and Selenops marcanoi Alayón-García, 1992 are described for the first time, and the females of Selenops phaselus Muma, 1953 and Selenops geraldinae Corronca, 1996 are described for the first time. Almost all species are redescribed, barring Cuban endemics and a few species recently described. New illustrations are provided, including those of the internal female copulatory organs, many of which are illustrated for the first time. A key to species is also provided as are new distributional records.

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' continued innovation that results in more effective products for the advanced biofuel market.« less

Cross dimerization of amyloid-β and αsynuclein proteins in aqueous environment: a molecular dynamics simulations study.

PubMed

Jose, Jaya C; Chatterjee, Prathit; Sengupta, Neelanjana

2014-01-01

Self-assembly of the intrinsically unstructured proteins, amyloid beta (Aβ) and alpha synclein (αSyn), are associated with Alzheimer's Disease, and Parkinson's and Lewy Body Diseases, respectively. Importantly, pathological overlaps between these neurodegenerative diseases, and the possibilities of interactions between Aβ and αSyn in biological milieu emerge from several recent clinical reports and in vitro studies. Nevertheless, there are very few molecular level studies that have probed the nature of spontaneous interactions between these two sequentially dissimilar proteins and key characteristics of the resulting cross complexes. In this study, we have used atomistic molecular dynamics simulations to probe the possibility of cross dimerization between αSyn1-95 and Aβ1-42, and thereby gain insights into their plausible early assembly pathways in aqueous environment. Our analyses indicate a strong probability of association between the two sequences, with inter-protein attractive electrostatic interactions playing dominant roles. Principal component analysis revealed significant heterogeneity in the strength and nature of the associations in the key interaction modes. In most, the interactions of repeating Lys residues, mainly in the imperfect repeats 'KTKEGV' present in αSyn1-95 were found to be essential for cross interactions and formation of inter-protein salt bridges. Additionally, a hydrophobicity driven interaction mode devoid of salt bridges, where the non-amyloid component (NAC) region of αSyn1-95 came in contact with the hydrophobic core of Aβ1-42 was observed. The existence of such hetero complexes, and therefore hetero assembly pathways may lead to polymorphic aggregates with variations in pathological attributes. Our results provide a perspective on development of therapeutic strategies for preventing pathogenic interactions between these proteins.

Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins.

PubMed

Flavin, William P; Bousset, Luc; Green, Zachary C; Chu, Yaping; Skarpathiotis, Stratos; Chaney, Michael J; Kordower, Jeffrey H; Melki, Ronald; Campbell, Edward M

2017-10-01

Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis. We observe that the ability to induce vesicle rupture is a common feature of α-synuclein (α-syn) assemblies, as assemblies derived from WT or familial disease-associated mutant α-syn all exhibited the ability to induce vesicle rupture. Similarly, different conformational strains of WT α-syn assemblies, but not monomeric or oligomeric forms, efficiently induced vesicle rupture following endocytosis. The ability to induce vesicle rupture was not specific to α-syn, as amyloid assemblies of tau and huntingtin Exon1 with pathologic polyglutamine repeats also exhibited the ability to induce vesicle rupture. We also observe that vesicles ruptured by α-syn are positive for the autophagic marker LC3 and can accumulate and fuse into large, intracellular structures resembling Lewy bodies in vitro. Finally, we show that the same markers of vesicle rupture surround Lewy bodies in brain sections from PD patients. These data underscore the importance of this conserved endocytic vesicle rupture event as a damaging mechanism of cellular invasion by amyloid assemblies of multiple neurodegenerative disease-associated proteins, and suggest that proteinaceous inclusions such as Lewy bodies form as a consequence of continued fusion of autophagic vesicles in cells unable to degrade ruptured vesicles and their amyloid contents.

Assay of Calcium Transients and Synapses in Rat Hippocampal Neurons by Kinetic Image Cytometry and High-Content Analysis: An In Vitro Model System for Postchemotherapy Cognitive Impairment.

PubMed

McDonough, Patrick M; Prigozhina, Natalie L; Basa, Ranor C B; Price, Jeffrey H

2017-07-01

Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days. Kinetic Image Cytometry™ (KIC™) methods were developed to quantify spontaneously occurring intracellular calcium transients representing the activity of the neurons, and high-content analysis (HCA) methods were developed to quantify the expression, colocalization, and puncta formed by synaptic proteins (postsynaptic density protein-95 [PSD-95] and presynaptic protein Synapsin-1 [Syn-1]). As quantified by KIC, FSK increased the occurrence and synchronization of the calcium transients indicating stimulatory effects on RHN activity, whereas TAM had inhibitory effects. As quantified by HCA, FSK also increased PSD-95 puncta and PSD-95:Syn-1 colocalization, whereas ES increased the puncta of both PSD-95 and Syn-1 with little effect on colocalization. The estrogen receptor antagonist FUL also increased PSD-95 puncta. In contrast, TAM reduced Syn-1 and PSD-95:Syn-1 colocalization, consistent with its inhibitory effects on the calcium transients. Thus TAM reduced activity and synapse formation by the RHNs, which may relate to the ability of this agent to cause PCCI. The results illustrate that KIC and HCA can be used to quantify neurotoxic and neuroprotective effects of chemicals in RHNs to investigate mechanisms and potential therapeutics for PCCI.

Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Merida (Venezuela).

PubMed

Uzcátegui, Euderruh; Valery, Lenin; Uzcátegui, Lilia; Gómez Pérez, Roald; Marquina, David; Baptista, Trino

2015-06-01

The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged > or =18 years from the Libertador district in Merida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients' self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

Effects of synchronous versus asynchronous mode of propulsion on wheelchair basketball sprinting.

PubMed

Faupin, Arnaud; Borel, Benoit; Meyer, Christophe; Gorce, Philippe; Watelain, Eric

2013-11-01

This study aimed to first investigate synchronous (SYN) versus asynchronous (ASY) mode of propulsion and, second, investigate the wheel camber effects on sprinting performance as well as temporal parameters. Seven wheelchair basketball players performed four maximal eight-second sprints on a wheelchair ergometer. They repeated the test according to two modes of propulsion (SYN and ASY) and two wheel cambers (9° and 15°). The mean maximal velocity and push power output was greater in the synchronous mode compared to the asynchronous mode for both camber angles. However, the fluctuation in the velocity profile is inferior for ASY versus SYN mode for both camber angles. Greater push time/cycle time (Pt/Ct) and arm frequency (AF) for synchronous mode versus asynchronous mode and inversely, lesser Ct and rest time (Rt) values for the synchronous mode, for which greater velocity were observed. SYN mode leads to better performance than ASY mode in terms of maximal propulsion velocity. However, ASY propulsion allows greater continuity of the hand-rim force application, reducing fluctuations in the velocity profile. The camber angle had no effect on ASY and SYN mean maximal velocity and push power output. The study of wheelchair propulsion strategies is important for better understanding physiological and biomechanical impacts of wheelchair propulsion for individuals with disabilities. From a kinematical point of view, this study highlights synchronous mode of propulsion to be more efficient, with regards to mean maximal velocity reaching during maximal sprinting exercises. Even if this study focuses on well-trained wheelchair athletes, results from this study could complement the knowledge on the physiological and biomechanical adaptations to wheelchair propulsion and therefore, might be interesting for wheelchair modifications for purposes of rehabilitation.

CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

PubMed Central

Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S.; Toledo, Jon B.; Weintraub, Daniel; Galasko, Douglas R.; Irwin, David J.; Van Deerlin, Vivianna; Chen-Plotkin, Alice S.; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M.; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Trojanowski, John Q.; Shaw, Leslie M.

2016-01-01

The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.

PubMed

Datta, Dibyadyuti; Bansal, Geetha P; Gerloff, Dietlind L; Ellefsen, Barry; Hannaman, Drew; Kumar, Nirbhay

2017-01-05

Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV). Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms. In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses. DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP). EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine. Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated). Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines. Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Marker-free transgenic rice expressing the vegetative insecticidal protein (Vip) of Bacillus thuringiensis shows broad insecticidal properties.

PubMed

Pradhan, Subrata; Chakraborty, Anirban; Sikdar, Narattam; Chakraborty, Saikat; Bhattacharyya, Jagannath; Mitra, Joy; Manna, Anulina; Dutta Gupta, Snehasish; Sen, Soumitra Kumar

2016-10-01

Genetically engineered rice lines with broad insecticidal properties against major lepidopteran pests were generated using a synthetic, truncated form of vegetative insecticidal protein (Syn vip3BR) from Bacillus thuringiensis. The selectable marker gene and the redundant transgene(s) were eliminated through Cre/ lox mediated recombination and genetic segregation to make consumer friendly Bt -rice. For sustainable resistance against lepidopteran insect pests, chloroplast targeted synthetic version of bioactive core component of a vegetative insecticidal protein (Syn vip3BR) of Bacillus thuringiensis was expressed in rice under the control of green-tissue specific ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit gene promoter. The transgenic plants (in Oryza sativa indica Swarna cultivar) showed high insect mortality rate in vitro against major rice pests, yellow stem borer (Scirpophaga incertulas), rice leaf folder (Cnaphalocrocis medinalis) and rice horn caterpillar (Melanitis leda ismene) in T1 generation, indicating insecticidal potency of Syn vip3BR. Under field conditions, the T1 plants showed considerable resistance against leaf folders and stem borers. The expression cassette (vip-lox-hpt-lox) as well as another vector with chimeric cre recombinase gene under constitutive rice ubiquitin1 gene promoter was designed for the elimination of selectable marker hygromycin phosphotransferase (hptII) gene. Crossing experiments were performed between T1 plants with single insertion site of vip-lox-hpt-lox T-DNA and one T1 plant with moderate expression of cre recombinase with linked bialaphos resistance (syn bar) gene. Marker gene excision was achieved in hybrids with up to 41.18 % recombination efficiency. Insect resistant transgenic lines, devoid of selectable marker and redundant transgene(s) (hptII + cre-syn bar), were established in subsequent generation through genetic segregation.

Revision of the East Mediterranean Orthomus (Coleoptera, Carabidae, Pterostichini), with description of Parorthomus gen. n. socotranus sp. n. from Socotra Island and key to the Old World genera of subtribe Euchroina

PubMed Central

Guéorguiev, Borislav; Wrase, David W.; Farkač, Jan

2014-01-01

Abstract The East Mediterranean species of Orthomus Chaudoir, 1838 are revised. The type series of Feronia longula Reiche & Saulcy, 1855, F. berytensis Reiche & Saulcy, 1855, F. proelonga Reiche & Saulcy, 1855, Orthomus longior Chaudoir, 1873, O. sidonicus Chaudoir, 1873, and O. berytensis akbensis Mateu, 1955 were studied and lectotypes for the first four are designated. Also, the following nomenclatural acts are proposed: Feronia proelonga Reiche & Saulcy, 1855, syn. n. of Orthomus berytensis (Reiche & Saulcy, 1855); Feronia elongata Chaudoir, 1859, syn. n. of Orthomus berytensis (Reiche & Saulcy, 1855); Orthomus sidonicus Chaudoir, 1873, syn. n. of Orthomus longior Chaudoir, 1873; Orthomus velocissimus andalusiacus Mateu, 1957, syn. n. of Orthomus velocissimus akbensis Mateu, 1955, new assignment for Orthomus berytensis akbensis Mateu, 1955. As a result, three species of the genus inhabit the East Mediterranean biogeographical region: O. berytensis, O. longior, and O. longulus. A key to these three species is given. O. longior is recorded for Turkey and Syria for the first time. In addition, a new synonymy of two West Mediterranean taxa is proposed: O. szekessyi (Jedlička, 1956), syn. n. of O. balearicus (Piochard de la Brûlerie, 1868), and a new genus and a species are described: Parorthomus gen. n. socotranus sp. n. (type locality: Republic of Yemen, Socotra Archipelago, Socotra Island, Fimihin env., 530 m.a.s.l.). Illustrations of the species dealt with here are provided including external characters, habitus, mentum and submentum, and genitalia are provided. Nine genera of the “African Series” of subtribe Euchroina Chaudoir, 1874 are keyed for the first time. Checklists of the species of Orthomus and of the Old World euchroine genera are given. PMID:25147463

VPS41, a protein involved in lysosomal trafficking, is protective in C. elegans and mammalian cellular models of Parkinson's disease

PubMed Central

Ruan, Qingmin; Harrington, Adam J.; Caldwell, Kim A.; Caldwell, Guy A.; Standaert, David G.

2009-01-01

VPS41 is a protein identified as a potential therapeutic target for Parkinson's disease (PD) as a result of a high-throughput RNAi screen in C. elegans. VPS41 has a plausible mechanistic link to the pathogenesis of PD, as in yeast it is known to participate in trafficking of proteins to the lysosomal system and several recent lines of evidence have pointed to the importance of lysosomal system dysfunction in the neurotoxicity of alpha-synuclein (α-syn). We found that expression of the human form of VPS41 (hVPS41) prevents dopamine (DA) neuron loss induced by α-syn overexpression and 6-hydroxydopamine (6-OHDA) neurotoxicity in C. elegans. In SH-SY5Y neuroblastoma cell lines stably transfected with hVPS41, we determined that presence of this protein conferred protection against the neurotoxins 6-OHDA and rotenone. Overexpression of hVPS41 did not alter the mitochondrial membrane depolarization induced by these neurotoxins. hVPS41 did, however, block downstream events in the apoptotic cascade including activation of caspase-9 and caspase-3, and PARP cleavage. We also observed that hVPS41 reduced the accumulation of insoluble high molecular weight forms of α-syn in SH-SY5Y cells after treatment with rotenone. These data show that hVPS41 is protective against both α-syn and neurotoxic-mediated injury in invertebrate and cellular models of PD. These protective functions may be related to enhanced clearance of misfolded or aggregated protein, including α-syn. Our studies indicate that hVPS41 may be a useful target for developing therapeutic strategies for human PD. PMID:19850127

Snow Never Falls on Satellite Radiometers: A Compelling Alternative to Ground Observations

NASA Astrophysics Data System (ADS)

Hinkelman, L. M.; Lapo, K. E.; Cristea, N. C.; Lundquist, J. D.

2014-12-01

Snowmelt is an important source of surface water for ecosystems, river flow, drinking water, and production of hydroelectric power. Thus accurate modeling of snow accumulation and melt is needed to improve our understanding of the impact of climate change on mountain snowpack and for use in water resource forecasting and management decisions. One of the largest potential sources of uncertainty in modeling mountain snow is the net radiative flux. This is because while net irradiance makes up the majority of the surface energy balance, it is one of the most difficult forcings to measure at remote mountain locations. Here we investigate the use of irradiances derived from satellite measurements in the place of surface observations. NASA's Clouds and the Earth's Radiant Energy System (CERES) SYN satellite product provides longwave and shortwave irradiances at the ground on three-hourly temporal and one degree spatial resolution.Although the low resolution of these data is a drawback, their availability over the entire globe for the full period of March 2000 through December 2010 (and beyond, as processing continues) makes them an attractive option for use in modeling. We first assessed the accuracy of the SYN downwelling solar and longwave fluxes by comparison to measurements at NOAA's Surface Radiation Network (SURFRAD) reference stations and at remote mountain stations. The performance of several snow models of varying complexity when using SYN irradiances as forcing data was then evaluated. Simulated snow water equivalent and runoff from cases using SYN data fell in the range of those from simulations forced with irradiances from higher quality surface observations or more highly-regarded empirical methods. We therefore judge the SYN irradiances to be suitable for use in snowmelt modeling and preferable to in situ measurements of questionable quality.

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.

Cost of ventral hernia repair using biologic or synthetic mesh.

PubMed

Totten, Crystal F; Davenport, Daniel L; Ward, Nicholas D; Roth, J Scott

2016-06-15

Patients undergoing ventral hernia repair (VHR) with biologic mesh (BioM) have higher hospital costs compared with synthetic mesh (SynM). This study compares 90-d pre- and post-VHR hospital costs (180-d) among BioM and SynM based on infection risk. This retrospective National Surgical Quality Improvement Program study matched patient perioperative risk with resource utilization cost for a consecutive series of VHR repairs. Patient infection risks, clinical and financial outcomes were compared in unmatched SynM (n = 303) and BioM (n = 72) groups. Propensity scores were used to match 35 SynM and BioM pairs of cases with similar infection risk for outcomes analysis. BioM patients in the unmatched group were older with higher American Society of Anesthesiologists (ASA) and wound classification, and they more frequently underwent open repairs for recurrent hernias. Wound surgical site infections were more frequent in unmatched BioM patients (P = 0.001) as were 180-d costs ($43.8k versus $14.0k, P < 0.001). Propensity matching resulted in 31 clean cases. In these low-risk patients, wound occurrences and readmissions were identical, but 180-d costs remained higher ($31.8k versus $15.5k, P < 0.001). There were no differences in hospital 180-d diagnostic, emergency room, intensive care unit, floor, pharmacy, or therapeutic costs. However, 180-d operating room services and supply costs were higher in the BioM group ($21.1k versus $7.1k, P < 0.001). BioM is used more commonly in hernia repairs involving higher wound class and ASA scores and recurrent hernias. Clinical outcomes after low-risk VHRs are similar; SynM utilization in low-risk hernia repairs was more cost-effective. Published by Elsevier Inc.

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.

A spontaneous deletion of α-synuclein is associated with an increase in CB1 mRNA transcript and receptor expression in the hippocampus and amygdala: effects on alcohol consumption

PubMed Central

López-Jiménez, Alejandro; Walter, Nicole A. R.; Giné, Elena; Santos, Ángel; Echeverry-Alzate, Victor; Bühler, Kora-Mareen; Olmos, Pedro; Giezendanner, Stéphanie; Moratalla, Rosario; Montoliu, Lluis; Buck, Kari J.; López-Moreno, Jose Antonio

2014-01-01

α-Synuclein (α-syn) protein and endocannabinoid CB1 receptors are primarily located in presynaptic terminals. An association between α-syn and CB1 receptors has recently been established in Parkinson’s disease, but it is completely unknown whether there is an association between these two proteins in alcohol addiction. Therefore, we aimed to examine the α-syn mRNA transcript and protein expression levels in the prefrontal cortex, striatum, amygdala and hippocampus. These brain regions are the most frequently implicated in alcohol and other drug addiction. In these studies, we used C57BL/6 mice carrying a spontaneous deletion of the α-syn gene (C57BL/6Snca−/−) and their respective controls (C57BL/6Snca+/+). These animals were monitored for spontaneous alcohol consumption (3–10%) and their response to a hypnotic-sedative dose of alcohol (3 g/kg) was also assessed. Compared with the C57BL/6Snca+/+ mice, we found that the C57BL/6Snca−/− mice exhibited a higher expression level of the CB1 mRNA transcript and CB1 receptor in the hippocampus and amygdala. Furthermore, C57BL/6Snca−/− mice showed an increase in alcohol consumption when offered a 10% alcohol solution. There was no significant difference in sleep time after the injection of 3 g/kg alcohol. These results are the first to reveal an association between α-syn and the CB1 receptor in the brain regions that are most frequently implicated in alcohol and other drug addictions. PMID:23345080

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

Derivation of mouse embryonic stem cell lines from tyrosine hydroxylase reporter mice crossed with a human SNCA transgenic mouse model of Parkinson's disease.

PubMed

Chumarina, Margarita; Azevedo, Carla; Bigarreau, Julie; Vignon, Clémentine; Kim, Kwang-Soo; Li, Jia-Yi; Roybon, Laurent

2017-03-01

Mouse embryonic stem cell (mESC) lines were derived by crossing heterozygous transgenic (tg) mice expressing green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase (TH) promoter, with homozygous alpha-synuclein (aSYN) mice expressing human mutant SNCA A53T under the control of the mouse Prion promoter (MoPrP), or wildtype (WT) mice. The expression of GFP and human aSYN was validated by immunocytochemistry in midbrain neuron cultures upon differentiation of mESC lines using stromal cell-derived inducing activity. These mESC lines can help to study the impact of human aSYN expression in neurons and oligodendrocytes, and also trace GFP-expressing midbrain neurons. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

- Wave Spectrum of Carbonyl Diazide in Pursuit of Diazirinone

NASA Astrophysics Data System (ADS)

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

2013-06-01

Pyrolysis of carbonyl diazide (CO(N_3)_2) has been shown to give diazirinone (CON_2). While diazirione decomposes over the course of a few hours under terrestrial conditions, there is the possibility for it to exist in space. In the pursuit of obtaining a rotational spectrum for diazirinone, we have started with the rotational spectroscopy of its immediate precursor, carbonyl diazide. Carbonyl diazide is highly explosive, and requires careful synthesis. Spectra in the range of 260-360 GHz were collected at room temperature and at -60°C. Ab initio calculations at the CCSD/cc-pVDZ level predict that the conformation where both azide groups are syn to the carbonyl is preferred. A second conformation, where one azide is syn and one is anti, is calculated to lie about 2 kcal/ mol higher in energy. Pure rotational transitions for the ground state and multiple low-lying excited vibrational states of the syn- syn conformation are readily observed and assigned. X. Zeng, H. Beckers, H. Willner and J. F. Stanton, Angew. Chem. Int. Ed. 50 (2011), 1720-1723 A. M. Nolan, B. K. Amberger, B. J. Esselman, V. S. Thimmakondu, J. F. Stanton, R. C. Woods, and R. J. McMahon, Inorg. Chem. 51 (2012), 9846-9851

The involvement of dityrosine crosslinking in α-synuclein assembly and deposition in Lewy Bodies in Parkinson’s disease

PubMed Central

Al-Hilaly, Youssra K.; Biasetti, Luca; Blakeman, Ben J. F.; Pollack, Saskia J.; Zibaee, Shahin; Abdul-Sada, Alaa; Thorpe, Julian R.; Xue, Wei-Feng; Serpell, Louise C.

2016-01-01

Parkinson’s disease (PD) is characterized by intracellular, insoluble Lewy bodies composed of highly stable α-synuclein (α-syn) amyloid fibrils. α-synuclein is an intrinsically disordered protein that has the capacity to assemble to form β-sheet rich fibrils. Oxidiative stress and metal rich environments have been implicated in triggering assembly. Here, we have explored the composition of Lewy bodies in post-mortem tissue using electron microscopy and immunogold labeling and revealed dityrosine crosslinks in Lewy bodies in brain tissue from PD patients. In vitro, we show that dityrosine cross-links in α-syn are formed by covalent ortho-ortho coupling of two tyrosine residues under conditions of oxidative stress by fluorescence and confirmed using mass-spectrometry. A covalently cross-linked dimer isolated by SDS-PAGE and mass analysis showed that dityrosine dimer was formed via the coupling of Y39-Y39 to give a homo dimer peptide that may play a key role in formation of oligomeric and seeds for fibril formation. Atomic force microscopy analysis reveals that the covalent dityrosine contributes to the stabilization of α-syn assemblies. Thus, the presence of oxidative stress induced dityrosine could play an important role in assembly and toxicity of α-syn in PD. PMID:27982082

Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products

DOE PAGES

Green, Amy M.; Barber, Victoria P.; Fang, Yi; ...

2017-11-06

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH 3CHOO. IR excitation of selectively deuterated syn-CD 3CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn-CD 3CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, whichmore » is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ~10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. Lastly, at 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn-CH 3CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ~50.« less

Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study.

PubMed

Kruse, Niels; Persson, Staffan; Alcolea, Daniel; Bahl, Justyna M C; Baldeiras, Ines; Capello, Elisabetta; Chiasserini, Davide; Bocchio Chiavetto, Luisella; Emersic, Andreja; Engelborghs, Sebastiaan; Eren, Erden; Fladby, Tormod; Frisoni, Giovanni; García-Ayllón, María-Salud; Genc, Sermin; Gkatzima, Olymbia; Heegaard, Niels H H; Janeiro, André M; Kováčech, Branislav; Kuiperij, H Bea; Leitão, Maria J; Lleó, Alberto; Martins, Madalena; Matos, Mafalda; Mollergard, Hanne M; Nobili, Flavio; Öhrfelt, Annika; Parnetti, Lucilla; de Oliveira, Catarina Resende; Rot, Uros; Sáez-Valero, Javier; Struyfs, Hanne; Tanassi, Julia T; Taylor, Peggy; Tsolaki, Magda; Vanmechelen, Eugeen; Verbeek, Marcel M; Zilka, Norbert; Blennow, Kaj; Zetterberg, Henrik; Mollenhauer, Brit

2015-09-01

Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program - Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given. Copyright © 2015 Elsevier Inc. All rights reserved.

Revision of the subgenus Aleochara Gravenhorst of the parasitoid rove beetle genus Aleochara Gravenhorst of Japan (Coleoptera: Staphylinidae: Aleocharinae).

PubMed

Yamamoto, Shûhei; Maruyama, Munetoshi

2016-04-08

The Japanese members of the subgenus Aleochara Gravenhorst, 1802 of the genus Aleochara Gravenhorst, 1802 are revised. Six species are recognized: Aleochara (Aleochara) coreana Bernhauer, 1926; A. (A.) curtula (Goeze, 1777); A. (A.) lata Gravenhorst, 1802; A. (A.) parens Sharp, 1874; A. (A.) postica Walker, 1858 [= A. (A.) clavigera Sharp, 1874, n. syn.; A. (A.) nitouensis Bernhauer, 1935, n. syn.; A. (A.) marginicollis Cameron, 1942, n. syn.], and; A. (A.) yaeyamensis n. sp. (Yaeyama Islands, the Ryûkyûs). We recognize A. niponensis Sharp, 1888, sp. rev., currently synonymized under A. clavigera, as a valid species and transfer it to the subgenus Xenochara Mulsant & Rey, 1874. "A. (A.)" kochi Bernhauer, 1941 [="A. (A.)" globus Pace, 1999, n. syn.] is excluded from Aleochara and re-assigned instead to Paraleochara Cameron, 1920. Paraleochara is new to the Palearctic region, and Paraleochara kochi (Bernhauer, 1941), n. comb. represents the second species of the genus. Lectotypes of A. niponensis, A. parens, and A.discoidea are designated. All species are described, keyed, and figured, with habitus photographs. Line drawings of the adult mouth parts of A. (A.) curtula (Goeze, 1777) are shown. The diversity, distribution, and phylogenetic relationships of the subgenus in Japan are also discussed.

Insights on the genus Acronymolpus Samuelson with new synonymies and exclusion of Stethotes Baly from the fauna of New Caledonia (Coleoptera, Chrysomelidae, Eumolpinae).

PubMed

Gómez-Zurita, Jesús

2017-01-01

In this work, several taxonomic problems affecting the recently erected genus Acronymolpus Samuelson, 2015, endemic to New Caledonia, are addressed. Two of the three New Caledonian species described in Stethotes Baly are transferred to Acronymolpus and their priority is recognized over the names proposed in the revision of this genus. Moreover, different forms of Acronymolpus always found in sympatry, one reddish and larger, and the other black and smaller, were each given species status in that revision, but they are recognized here as the females and males, respectively, of the same species. The taxonomic summary of these discoveries is: (i) A. bertiae (Jolivet, Verma & Mille, 2007), comb. n. = A. meteorus Samuelson, 2015, syn. n. , and A. turbo Samuelson, 2015, syn. n. ; and (ii) A. jourdani (Jolivet, Verma & Mille, 2013), comb. n. = A. gressitti Samuelson, 2015, syn. n. , and A. joliveti Samuelson, 2015, syn. n. New distribution data and the male genitalia and the spermatheca of the two valid species of Acronymolpus are described for the first time with reference to taxonomically important characters. Finally, the last New Caledonian species described in Stethotes is recognized here as a member of the endemic genus Taophila Heller: T. mandjeliae (Jolivet, Verma & Mille, 2010), comb. n.

Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products

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

Green, Amy M.; Barber, Victoria P.; Fang, Yi

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH 3CHOO. IR excitation of selectively deuterated syn-CD 3CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn-CD 3CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, whichmore » is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ~10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. Lastly, at 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn-CH 3CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ~50.« less

Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products.

PubMed

Green, Amy M; Barber, Victoria P; Fang, Yi; Klippenstein, Stephen J; Lester, Marsha I

2017-11-21

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH 3 CHOO. IR excitation of selectively deuterated syn -CD 3 CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn -CD 3 CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, which is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ∼10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. At 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn -CH 3 CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ∼50.

Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products

PubMed Central

Green, Amy M.; Barber, Victoria P.; Fang, Yi; Klippenstein, Stephen J.; Lester, Marsha I.

2017-01-01

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH3CHOO. IR excitation of selectively deuterated syn-CD3CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn-CD3CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, which is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ∼10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. At 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn-CH3CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ∼50. PMID:29109292

[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

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.

The near-UV absorber OSSO and its isomers.

PubMed

Wu, Zhuang; Wan, Huabin; Xu, Jian; Lu, Bo; Lu, Yan; Eckhardt, André K; Schreiner, Peter R; Xie, Changjian; Guo, Hua; Zeng, Xiaoqing

2018-05-01

Disulfur dioxide, OSSO, has been proposed as the enigmatic "near-UV absorber" in the yellowish atmosphere of Venus. However, the fundamentally important spectroscopic properties and photochemistry of OSSO are scarcely documented. By either condensing gaseous SO or 266 laser photolysis of an S2O2 complex in Ar or N2 at 15 K, syn-OSSO, anti-OSSO, and cyclic OS([double bond, length as m-dash]O)S were identified by IR and UV/Vis spectroscopy for the first time. The observed absorptions (λmax) for OSSO at 517 and 390 nm coincide with the near-UV absorption (320-400 nm) found in the Venus clouds by photometric measurements with the Pioneer Venus orbiter. Subsequent UV light irradiation (365 nm) depletes syn-OSSO and anti-OSSO and yields a fourth isomer, syn-OSOS, with concomitant dissociation into SO2 and elemental sulfur.

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.

Three new species of Ametadoria Townsend (Diptera: Tachinidae) from Area de Conservación Guanacaste, Costa Rica

PubMed Central

Wood, D. Monty; Smith, M. Alex; Hallwachs, Winnie; Janzen, Daniel

2015-01-01

Abstract We describe three new species in the genus Ametadoria Townsend from Area de Conservación Guanacaste (ACG), Costa Rica. All three were reared from wild-caught Zygaenidae and Lacturidae caterpillars. We provide a concise description of each species using morphology, life history and molecular data, with photographic documentation. The new species are authored and described by Fleming and Wood: Ametadoria karolramosae sp. nov., Ametadoria leticiamartinezae sp. nov., and Ametadoria mauriciogurdiani sp. nov. The following are proposed by Wood as new synonyms of Ametadoria Townsend: Adidyma Townsend syn. nov., and Abolodoria Townsend syn. nov. The following new combinations occur as a result of these new synonymies: Ametadoria abdominalis (Townsend) comb. nov., Ametadoria austrina (Coquillett) comb. nov., Ametadoria humilis (Wulp) comb. nov., Ametadoria misella (Wulp) comb. nov. Ametadoria adversa (Townsend) is proposed as a junior synonym of ​Ametadoria unispinosa Townsend, syn. nov​. PMID:26379458

A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands.

PubMed

Das, Samir; Nag, Arundhati; Liang, JingXin; Bunck, David N; Umeda, Aiko; Farrow, Blake; Coppock, Matthew B; Sarkes, Deborah A; Finch, Amethist S; Agnew, Heather D; Pitram, Suresh; Lai, Bert; Yu, Mary Beth; Museth, A Katrine; Deyle, Kaycie M; Lepe, Bianca; Rodriguez-Rivera, Frances P; McCarthy, Amy; Alvarez-Villalonga, Belen; Chen, Ann; Heath, John; Stratis-Cullum, Dimitra N; Heath, James R

2015-11-02

We describe a general synthetic strategy for developing high-affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope of interest is synthesized as a polypeptide, with a detection biotin tag and a strategically placed azide (or alkyne) presenting amino acid. This synthetic epitope (SynEp) is incubated with a library of complementary alkyne or azide presenting peptides. Library elements that bind the SynEp in the correct orientation undergo the Huisgen cycloaddition, and are covalently linked to the SynEp. Hit peptides are tested against the full-length protein to identify the best binder. We describe development of epitope-targeted linear or macrocycle peptide ligands against 12 different diagnostic or therapeutic analytes. The general epitope targeting capability for these low molecular weight synthetic ligands enables a range of therapeutic and diagnostic applications, similar to those of monoclonal antibodies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recovery of choline oxidase activity by in vitro recombination of individual segments.

PubMed

Heinze, Birgit; Hoven, Nina; O'Connell, Timothy; Maurer, Karl-Heinz; Bartsch, Sebastian; Bornscheuer, Uwe T

2008-11-01

Initial attempts to express a choline oxidase from Arthrobacter pascens (APChO-syn) in Escherichia coli starting from a synthetic gene only led to inactive protein. However, activity was regained by the systematic exchange of individual segments of the gene with segments from a choline oxidase-encoding gene from Arthrobacter globiformis yielding a functional chimeric enzyme. Next, a sequence alignment of the exchanged segment with other choline oxidases revealed a mutation in the APChO-syn, showing that residue 200 was a threonine instead of an asparagine, which is, thus, crucial for confering enzyme activity and, hence, provides an explanation for the initial lack of activity. The active recombinant APChO-syn-T200N variant was biochemically characterized showing an optimum at pH 8.0 and at 37 degrees C. Furthermore, the substrate specificity was examined using N,N-dimethylethanolamine, N-methylethanolamine and 3,3-dimethyl-1-butanol.

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

Theoretical study of some nitrososulfamide compounds with antitumor activity.

PubMed

Djameleddine, Khatmi; Soumeya, Seridi; Fatiha, Madi

2004-09-30

The lowest-energy conformations of four 2-chloroethylnitrososulfamides were determined using the MM+ molecular mechanics method as implemented in Hyperchem 6.0. Some of the calculated structural parameters, angles and bonds lengths were compared with the crystal structure data of N-nitroso-N-(2-chloroethyl)-N'-sulfamoyl- proline. Using MM+, AM1 and PM3 the anti conformation was predicted to be more stable than the syn conformation in each of these compounds. With these methods we found that the relative energy of the transition state (TS) was considerably higher, but with the ab initio method using RHF with minimal basic function STO-3G we found that the syn conformation is predicted to be slightly more stable. The determination of some atomic charges of a selection of atoms on the syn, anti and TS structures of the various compounds provided some details about the nature of the transition state.

The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise.

PubMed

Cai, Ming; Wang, Hong; Li, Jing-Jing; Zhang, Yun-Li; Xin, Lei; Li, Feng; Lou, Shu-Jie

2016-10-01

High fat diet (HFD)-induced obesity has been shown to reduce the levels of neuronal plasticity-related proteins, specifically brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN), in the hippocampus. However, the underlying mechanisms are not fully clear. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating gene expression and protein production by affecting stress signaling pathways and ER functions of protein folding and post-translational modification in peripheral tissues of obese rodent models. Additionally, HFD that is associated with hyperglycemia could induce hippocampal ERS, thus impairing insulin signaling and cognitive health in HFD mice. One goal of this study was to determine whether hyperglycemia and hyperlipidemia could cause hippocampal ERS in HFD-induced obese SD rats, and explore the potential mechanisms of ERS regulating hippocampal BDNF and SYN proteins production. Additionally, although regular aerobic exercise could reduce central inflammation and elevate hippocampal BDNF and SYN levels in obese rats, the regulated mechanisms are poorly understood. Nrf2-HO-1 pathways play roles in anti-ERS, anti-inflammation and anti-apoptosis in peripheral tissues. Therefore, the other goal of this study was to determine whether aerobic exercise could activate Nrf2-HO-1 in hippocampus to alleviate obesity-induced hippocampal ERS, which would lead to increased BDNF and SYN levels. Male SD rats were fed on HFD for 8weeks to establish the obese model. Then, 8weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that HFD-induced obesity caused hyperglycemia and hyperlipidemia, and significantly promoted hippocampal glucose transporter 3 (GLUT3) and fatty acid transport protein 1 (FATP1) protein expression. These results were associated with the activation of hippocampal ERS and ERS-mediated apoptosis. At the same time, we found that excessive hippocampal ERS not only significantly decreased proBDNF-the precursor of mature BDNF, but also attenuated p38/ERK-CREB signaling pathways and activated NLRP3-IL-1β pathways in obese rats. These results were associated with reduced BDNF and SYN protein production. However, these adverse changes were obviously reversed by aerobic exercise intervention through activating the Nrf2-HO-1 pathways. These results suggest that dietary obesity could induce hippocampal ERS in male SD rats, and excessive hippocampal ERS plays a critical role in decreasing the levels of BDNF and SYN. Moreover, aerobic exercise could activate hippocampal Nrf2 and HO-1 to relieve ERS and heighten BDNF and SYN production in obese rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Dosimetric evaluation of synthetic CT for magnetic resonance-only based radiotherapy planning of lung cancer.

PubMed

Wang, Hesheng; Chandarana, Hersh; Block, Kai Tobias; Vahle, Thomas; Fenchel, Matthias; Das, Indra J

2017-06-26

Interest in MR-only treatment planning for radiation therapy is growing rapidly with the emergence of integrated MRI/linear accelerator technology. The purpose of this study was to evaluate the feasibility of using synthetic CT images generated from conventional Dixon-based MRI scans for radiation treatment planning of lung cancer. Eleven patients who underwent whole-body PET/MR imaging following a PET/CT exam were randomly selected from an ongoing prospective IRB-approved study. Attenuation maps derived from the Dixon MR Images and atlas-based method was used to create CT data (synCT). Treatment planning for radiation treatment of lung cancer was optimized on the synCT and subsequently copied to the registered CT (planCT) for dose calculation. Planning target volumes (PTVs) with three sizes and four different locations in the lung were planned for irradiation. The dose-volume metrics comparison and 3D gamma analysis were performed to assess agreement between the synCT and CT calculated dose distributions. Mean differences between PTV doses on synCT and CT across all the plans were -0.1% ± 0.4%, 0.1% ± 0.5%, and 0.4% ± 0.5% for D95, D98 and D100, respectively. Difference in dose between the two datasets for organs at risk (OARs) had average differences of -0.14 ± 0.07 Gy, 0.0% ± 0.1%, and -0.1% ± 0.2% for maximum spinal cord, lung V20, and heart V40 respectively. In patient groups based on tumor size and location, no significant differences were observed in the PTV and OARs dose-volume metrics (p > 0.05), except for the maximum spinal-cord dose when the target volumes were located at the lung apex (p = 0.001). Gamma analysis revealed a pass rate of 99.3% ± 1.1% for 2%/2 mm (dose difference/distance to agreement) acceptance criteria in every plan. The synCT generated from Dixon-based MRI allows for dose calculation of comparable accuracy to the standard CT for lung cancer treatment planning. The dosimetric agreement between synCT and CT calculated doses warrants further development of a MR-only workflow for radiotherapy of lung cancer.

Study of the influence of the bridge on the magnetic coupling in cobalt(II) complexes.

PubMed

Fabelo, Oscar; Cañadillas-Delgado, Laura; Pasán, Jorge; Delgado, Fernando S; Lloret, Francesc; Cano, Joan; Julve, Miguel; Ruiz-Pérez, Catalina

2009-12-07

Two new cobalt(II) complexes of formula [Co(2)(bta)(H(2)O)(6)](n) x 2nH(2)O (1) and [Co(phda)(H(2)O)](n) x nH(2)O (2) [H(4)bta = 1,2,4,5-benzenetetracarboxylic acid, H(2)phda = 1,4-phenylenediacetic acid] have been characterized by single crystal X-ray diffraction. Compound 1 is a one-dimensional compound where the bta(4-) ligand acts as 2-fold connector between the cobalt(II) ions through two carboxylate groups in para-conformation. Triply bridged dicobalt(II) units occur within each chain, a water molecule, a carboxylate group in the syn-syn conformation, and an oxo-carboxylate with the mu(2)O(1);kappa(2)O(1),O(2) coordination mode acting as bridges. Compound 2 is a three-dimensional compound, where the phda(2-) group acts as a bridge through its two carboxylate groups, one of them adopting the mu-O,O' coordination mode in the syn-syn conformation and the other exhibiting the single mu(2)-O'' bridging mode. As in 1, chains of cobalt(II) ions occur in 2 with a water molecule, a syn-syn carboxylate group, and an oxo-carboxylate constitute the triply intrachain bridging skeleton. Each chain is linked to other four ones through the phda(2-) ligand, giving rise to the three-dimensional structure. The values of the intrachain cobalt-cobalt separation are 3.1691(4) (1) and 3.11499(2) A (2) whereas those across the phenyl ring of the extended bta(4-) (1) and phda(2-) (2) groups are 10.1120(6) and 11.4805(69 A, respectively. The magnetic properties of 1 and 2 have been investigated in the temperature range 1.9-300 K, and their analysis has revealed the occurrence of moderate intrachain ferromagnetic couplings [J = +5.4 (1) and +2.16 cm(-1) (2), J being the isotropic magnetic coupling parameter], the magnetic coupling through the extended bta(4-) and phda(2-) with cobalt-cobalt separations larger than 10 A being negligible. The nature and magnitude of the magnetic interactions between the high-spin cobalt(II) ions in 1 and 2 are compared to those of related systems and discussed as a function of the complementarity-countercomplementarity effects of the triple bridges.

A revision of the spider genus Selenops Latreille, 1819 (Arachnida, Araneae, Selenopidae) in North America, Central America and the Caribbean

PubMed Central

Crews, Sarah C.

2011-01-01

Abstract The spider genus Selenops Latreille, 1819 occurs in both the Old World and New World tropics and subtropics and contains nearly half of the species in the family Selenopidae Simon, 1897. In this paper the members of the genus Selenops found in North America, Central America, and on islands of the Caribbean are revised, excluding Cuban endemics. No taxonomic changes are currently made to the species from the southwestern United States. In total, 21 new species are described, including Selenops arikok sp. n., Selenops chamela sp. n., Selenops amona sp. n., Selenops baweka sp. n., Selenops bocacanadensis sp. n., Selenops enriquillo sp. n, Selenops ixchel sp. n., Selenops huetocatl sp. n., Selenops kalinago sp. n., Selenops oviedo sp. n., Selenops morro sp. n., Selenops denia sp. n., Selenops duan sp. n., Selenops malinalxochitl sp. n., Selenops oricuajo sp. n., Selenops petenajtoy sp. n., Selenops guerrero sp. n., Selenops makimaki sp. n., Selenops souliga sp. n., Selenops wilmotorum sp. n., and Selenops wilsoni sp. n. Six species names were synonymized: Selenops lunatus Muma, 1953 syn. n. = Selenops candidus Muma, 1953; Selenops tehuacanus Muma 1953 syn. n., Selenops galapagoensis Banks, 1902 syn. n. and Selenops vagabundus Kraus, 1955 syn. n. = Selenops mexicanus Keyserling, 1880; Selenops santibanezi Valdez-Mondragón, 2010 syn. n. = Selenops nigromaculatus Keyserling, 1880; and Selenops salvadoranus Chamberlin, 1925 syn. n. = Selenops bifurcatus Banks, 1909. Lectotypes are designated for the following three species: Selenops marginalis F. O. Pickard-Cambridge, 1900 (♂), Selenops morosus Banks, 1898 (♂), and Selenops mexicanus Keyserling, 1880 (♀). The female neotype is designated for Selenops aissus Walckenaer, 1837. The males of Selenops bani Alayón-García, 1992 and Selenops marcanoi Alayón-García, 1992 are described for the first time, and the females of Selenops phaselus Muma, 1953 and Selenops geraldinae Corronca, 1996 are described for the first time. Almost all species are redescribed, barring Cuban endemics and a few species recently described. New illustrations are provided, including those of the internal female copulatory organs, many of which are illustrated for the first time. A key to species is also provided as are new distributional records. PMID:21852919

Ctenodontina Enderlein, 1914 (Diptera, Asilidae, Asilinae): new combinations, synonyms, new species and new records for Argentina.

PubMed

Vieira, Rodrigo; Landa, José Manuel Ayala; Rafael, José Albertino

2017-01-06

Ctenodontina Enderlein is reported for the first time in Argentina. A new species, C. sagta sp. nov. (Argentina, Salta) is described. New combination is Ctenodontina baleta (Walker), comb. nov. with two synonimies: Pachychoeta caracasae Martin syn. nov. and Pachychoeta inca Martin syn. nov. The male and female terminalia of C. baleta (Walker). comb. nov. is illustrated and described for the first time and a key to species is presented.

Correlation between decreased CSF α-synuclein and Aβ₁₋₄₂ in Parkinson disease.

PubMed

Buddhala, Chandana; Campbell, Meghan C; Perlmutter, Joel S; Kotzbauer, Paul T

2015-01-01

Accumulation of misfolded α-synuclein (α-syn) protein in Lewy bodies and neurites is the cardinal pathologic feature of Parkinson disease (PD), but abnormal deposition of other proteins may also play a role. Cerebrospinal fluid (CSF) levels of proteins known to accumulate in PD may provide insight into disease-associated changes in protein metabolism and their relationship to disease progression. We measured CSF α-syn, amyloid β₁₋₄₂ (Aβ₁₋₄₂), and tau from 77 nondemented PD and 30 control participants. CSF α-syn and Aβ₁₋₄₂ were significantly lower in PD compared with controls. In contrast with increased CSF tau in Alzheimer disease, CSF tau did not significantly differ between PD and controls. CSF protein levels did not significantly correlate with ratings of motor function or performance on neuropsychological testing. As expected, CSF Aβ₁₋₄₂ inversely correlated with [(11)C]-Pittsburgh compound B (PiB) mean cortical binding potential, with PiB(+) PD participants having lower CSF Aβ₁₋₄₂ compared with PiB(-) PD participants. Furthermore, CSF α-syn positively correlated with Aβ₁₋₄₂ in PD participants but not in controls, suggesting a pathophysiologic connection between the metabolisms of these proteins in PD. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Re-Adaptation to 1-G of Pregnant Rats Following Exposure to Spaceflight or Centrifugation

NASA Technical Reports Server (NTRS)

Johnson, K. E.; Ronca, A. E.; Alberts, J. R.

2003-01-01

Late-pregnant rat dams were flown on a 9-day Space Shuttle mission or exposed to 1.5, 1.75 or 2-g centrifugation and compared with 1 .O-g vivarium controls. Exposure to altered gravity began on the 11th day and recovery occurred on the 20th day of the dams' 22-day pregnancy. In the 1 st experiment, comparisons were made between Flight (FLT), Synchronous (SYN; identically-housed) and Vivarium (VIV) controls. In the 2nd experiment, comparisons were made between dams centrifuged at 2-G, 1.75-G, 1.5-G, Rotational controls (1.08-G) or Stationary controls (1 G). Within three hours of recovery from either spaceflight or centrifugation, the dams' locomotor behavior was videotaped for 2 min. FLT dams showed dramatically reduced movement relative to both SYN and VIV control conditions, with significantly greater amounts of locomotor activity observed in SYN as compared to VIV dams. Significantly greater locomotor activity was observed in SYN as compared to VIV controls. In the second experiment, no differences were observed between dams exposed either 1, 1.5, 1.75, or 2-G. In both studies, the dams showed similar patterns of hindlimb rearing. Together, these findings provide quantitative evidence for decreased locomotor activity during re-adaptation to 1-g following spaceflight, but not centrifugation.

Taxonomic revision of New Guinea diving beetles of the Exocelina danae group, with the description of ten new species (Coleoptera, Dytiscidae, Copelatinae)

PubMed Central

Shaverdo, Helena; Sagata, Katayo; Balke, Michael

2016-01-01

Abstract Ten new species of Exocelina Broun, 1886 from New Guinea are described: Exocelina andakombensis sp. n., Exocelina garaina sp. n., Exocelina injiensis sp. n., Exocelina kabwumensis sp. n., Exocelina marawaga sp. n., Exocelina posmani sp. n., Exocelina tekadu sp. n., Exocelina varirata sp. n., Exocelina wareaga sp. n., and Exocelina woitapensis sp. n. All of them together with five already described species are united into the newly defined Exocelina danae-group (with Exocelina miriae-subgroup), a polyphyletic complex of related species with lateral setation on the median lobe. In the light of newly available material, all previously described species of the Exocelina rivulus-group are considered to belong to a single species, Exocelina damantiensis (Balke, 1998), which is now placed into the Exocelina danae-group, and three new synonyms are therefore proposed: Exocelina madangensis (Balke, 2001) syn. n., Exocelina patepensis (Balke, 1998) syn. n., and Exocelina rivulus (Balke, 1998) syn. n. Exocelina tarmluensis (Balke, 1998) syn. n. is a junior synonym of Exocelina danae (Balke, 1998). Redescription of Exocelina atratus (Balfour-Browne, 1939) is provided based on its type material. An identification key to all known species of the group is provided, and important diagnostic characters are illustrated. Data on the species distribution are given, showing that whilst most species are local endemics, Exocelina damantiensis is extremely widely distributed. PMID:27829789

Studies on the π-π stacking features of imidazole units present in a series of 5-amino-1-alkylimidazole-4-carboxamides

NASA Astrophysics Data System (ADS)

Ray, Sibdas; Das, Aniruddha

2015-06-01

Reaction of 2-ethoxymethyleneamino-2-cyanoacetamide with primary alkyl amines in acetonitrile solvent affords 1-substituted-5-aminoimidazole-4-carboxamides. Single crystal X-ray diffraction studies of these imidazole compounds show that there are both anti-parallel and syn-parallel π-π stackings between two imidazole units in parallel-displaced (PD) conformations and the distance between two π-π stacked imidazole units depends mainly on the anti/ syn-parallel nature and to some extent on the alkyl group attached to N-1 of imidazole; molecules with anti-parallel PD-stacking arrangements of the imidazole units have got vertical π-π stacking distance short enough to impart stabilization whereas the imidazole unit having syn-parallel stacking arrangement have got much larger π-π stacking distances. DFT studies on a pair of anti-parallel imidazole units of such an AICA lead to curves for 'π-π stacking stabilization energy vs. π-π stacking distance' which have got similarity with the 'Morse potential energy diagram for a diatomic molecule' and this affords to find out a minimum π-π stacking distance corresponding to the maximum stacking stabilization energy between the pair of imidazole units. On the other hand, a DFT calculation based curve for 'π-π stacking stabilization energy vs. π-π stacking distance' of a pair of syn-parallel imidazole units is shown to have an exponential nature.

Pre-existing oblique transfer zones and transfer/transform relationships in continental margins: New insights from the southeastern Gulf of Aden, Socotra Island, Yemen

NASA Astrophysics Data System (ADS)

Bellahsen, N.; Leroy, S.; Autin, J.; Razin, P.; d'Acremont, E.; Sloan, H.; Pik, R.; Ahmed, A.; Khanbari, K.

2013-11-01

Transfer zones are ubiquitous features in continental rifts and margins, as are transform faults in oceanic lithosphere. Here, we present a structural study of the Hadibo Transfer Zone (HTZ), located in Socotra Island (Yemen) in the southeastern Gulf of Aden. There, we interpret this continental transfer fault zone to represent a reactivated pre-existing structure. Its trend is oblique to the direction of divergence and it has been active from the early up to the latest stages of rifting. One of the main oceanic fracture zones (FZ), the Hadibo-Sharbithat FZ, is aligned with and appears to be an extension of the HTZ and is probably genetically linked to it. Comparing this setting with observations from other Afro-Arabian rifts as well as with passive margins worldwide, it appears that many continental transfer zones are reactivated pre-existing structures, oblique to divergence. We therefore establish a classification system for oceanic FZ based upon their relationship with syn-rift structures. Type 1 FZ form at syn-rift structures and are late syn-rift to early syn-OCT. Type 2 FZ form during the OCT formation and Type 3 FZ form within the oceanic domain, after the oceanic spreading onset. The latter are controlled by far-field forces, magmatic processes, spreading rates, and oceanic crust rheology.

Effects of cell penetrating Notch inhibitory peptide conjugated to elastin-like polypeptide on glioblastoma cells.

PubMed

Opačak-Bernardi, Teuta; Ryu, Jung Su; Raucher, Drazen

2017-07-01

Notch pathway was found to be activated in most glioblastomas (GBMs), underlining the importance of Notch in formation and recurrence of GBM. In this study, a Notch inhibitory peptide, dominant negative MAML (dnMAML), was conjugated to elastin-like polypeptide (ELP) for tumor targeted delivery. ELP is a thermally responsive polypeptide that can be actively and passively targeted to the tumor site by localized application of hyperthermia. This complex was further modified with the addition of a cell penetrating peptide, SynB1, for improved cellular uptake and blood-brain barrier penetration. The SynB1-ELP1-dnMAML was examined for its cellular uptake, cytotoxicity, apoptosis, cell cycle inhibition and the inhibition of target genes' expression. SynB1-ELP1-dnMAML inhibited the growth of D54 and U251 cells by inducing apoptosis and cell cycle arrest, especially in the presence of hyperthermia. Hyperthermia increased overall uptake of the polypeptide by the cells and enhanced the resulting pharmacological effects of dnMAML, showing the inhibition of targets of Notch pathway such as Hes-1 and Hey-L. These results confirm that dnMAML is an effective Notch inhibitor and combination with ELP may allow thermal targeting of the SynB1-ELP1-dnMAML complex in cancer cells while avoiding the dangers of systemic Notch inhibition.

Functional and Structural Characterization of a Cation-dependent O-Methyltransferase from the Cyanobacterium Synechocystis sp. Strain PCC 6803*S⃞

PubMed Central

Kopycki, Jakub Grzegorz; Stubbs, Milton T.; Brandt, Wolfgang; Hagemann, Martin; Porzel, Andrea; Schmidt, Jürgen; Schliemann, Willibald; Zenk, Meinhart H.; Vogt, Thomas

2008-01-01

The coding sequence of the cyanobacterium Synechocystis sp. strain PCC 6803 slr0095 gene was cloned and functionally expressed in Escherichia coli. The corresponding enzyme was classified as a cation- and S-adenosyl-l-methionine-dependent O-methyltransferase (SynOMT), consistent with considerable amino acid sequence identities to eukaryotic O-methyltransferases (OMTs). The substrate specificity of SynOMT was similar with those of plant and mammalian CCoAOMT-like proteins accepting a variety of hydroxycinnamic acids and flavonoids as substrates. In contrast to the known mammalian and plant enzymes, which exclusively methylate the meta-hydroxyl position of aromatic di- and trihydroxy systems, Syn-OMT also methylates the para-position of hydroxycinnamic acids like 5-hydroxyferulic and 3,4,5-trihydroxycinnamic acid, resulting in the formation of novel compounds. The x-ray structure of SynOMT indicates that the active site allows for two alternative orientations of the hydroxylated substrates in comparison to the active sites of animal and plant enzymes, consistent with the observed preferred para-methylation and position promiscuity. Lys3 close to the N terminus of the recombinant protein appears to play a key role in the activity of the enzyme. The possible implications of these results with respect to modifications of precursors of polymers like lignin are discussed. PMID:18502765

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.

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-order DNA architectures. Further, these two small unimolecular G-quadruplexes, which are distinct from each other and from parallel-stranded G-quadruplexes, provide novel targets for ligand recognition. Our results demonstrate that the double chain reversal loop connectivity identified previously by our laboratory within the Tetrahymena telomere d(T2G4)4 quadruplex, is a robust folding topology, since it has now also been observed within the d(G2T4G2CAG2GT4G2T) quadruplex. The identification of a G-(T-T) triad and a T-T-T triple, expands on the available recognition alignments for base triads and triples. Copyright 2001 Academic Press.

Revision of the genus Thyreocephalus and description of Afrus gen. nov. of Africa south of the Sahara (Coleoptera: Staphylinidae: Staphylininae).

PubMed

Janák, Jiří; Bordoni, Arnaldo

2015-11-02

A revision of the genus Thyreocephalus Guérin-Méneville, 1844 of Africa south of the Sahara is presented. A new genus Afrus gen. nov. was described with the type species Thyreocephalus spegazzinii Bernhauer, 1915, which resulted in following new combination: Afrus spegazzinii (Bernhauer, 1915), comb. nov. Eulissus collarti (Cameron, 1932) was transferred to Afrus. Based on a revision of types and of additional material, 32 species of the genus Thyreocephalus and two species of the genus Afrus are recognized in Africa south of the Sahara. All species are described or redescribed and illustrated, seven of them for the first time: Thyreocephalus camerunensis sp. nov., T. manfredi sp. nov., T. marginipennis sp. nov., T. meridioafricanus sp. nov., T. pseudoafricanus sp. nov., T. subcorticalis sp. nov. and T. tsingidianus sp. nov. Neotypes are designated for Eulissus ater Laporte, 1835, Xantholinus coeruleipennis Quedenfeldt, 1881, and X. interocularis Eppelsheim, 1895. Lectotypes are designated for Eulissus atlanticus Bernhauer, 1915, E. burgeoni Bernhauer, 1929, E. mokaensis Bernhauer, 1915, E. secretus Bernhauer, 1935, E. turneri Bernhauer, 1937, Xantholinus alluaudi Fauvel, 1907, X. mocquerysi Fauvel, 1903, X. pilosus Roth, 1851, Thyreocephalus diversiceps Bernhauer, 1936, and T. spegazzinii Bernhauer, 1915. Eulissus africanus Bernhauer, 1913, E. alluaudi (Fauvel, 1907) (originally described in Xantholinus Dejean, 1821), E. atlanticus Bernhauer, 1915, E. brunneiventris Tottenham, 1956, E. burgeoni Bernhauer, 1929, E. guineensis Bernhauer, 1912, E. mokaensis Bernhauer, 1915, E. secretus Bernhauer, 1935, E. strinatii Scheerpeltz, 1958, and Xantholinus nairobiensis Fauvel, 1907 were transferred to Thyreocephalus. Following synonymies are proposed: Thyreocephalus nairobiensis (Fauvel, 1907) = Eulissus turneri Bernhauer, 1937, syn. nov., Thyreocephalus interocularis (Eppelsheim, 1895) = Thyreocephalus diversiceps Bernhauer, 1936, syn. nov., Thyreocephalus mokaensis (Bernhauer, 1915) = Eulissus flaviventris Bernhauer, 1939, syn. nov. = Thyreocephalus semirufus Coiffait, 1968, syn. nov., Thyreocephalus mocquerysi (Fauvel, 1903) = Eulissus milliaui Bernhauer, 1932, syn. nov. The distribution of both genera in Africa south of Sahara is mapped and a key to species is presented.

Molecular phylogeny of the aquatic beetle family Noteridae (Coleoptera: Adephaga) with an emphasis on data partitioning strategies.

PubMed

Baca, Stephen M; Toussaint, Emmanuel F A; Miller, Kelly B; Short, Andrew E Z

2017-02-01

The first molecular phylogenetic hypothesis for the aquatic beetle family Noteridae is inferred using DNA sequence data from five gene fragments (mitochondrial and nuclear): COI, H3, 16S, 18S, and 28S. Our analysis is the most comprehensive phylogenetic reconstruction of Noteridae to date, and includes 53 species representing all subfamilies, tribes and 16 of the 17 genera within the family. We examine the impact of data partitioning on phylogenetic inference by comparing two different algorithm-based partitioning strategies: one using predefined subsets of the dataset, and another recently introduced method, which uses the k-means algorithm to iteratively divide the dataset into clusters of sites evolving at similar rates across sampled loci. We conducted both maximum likelihood and Bayesian inference analyses using these different partitioning schemes. Resulting trees are strongly incongruent with prior classifications of Noteridae. We recover variant tree topologies and support values among the implemented partitioning schemes. Bayes factors calculated with marginal likelihoods of Bayesian analyses support a priori partitioning over k-means and unpartitioned data strategies. Our study substantiates the importance of data partitioning in phylogenetic inference, and underscores the use of comparative analyses to determine optimal analytical strategies. Our analyses recover Noterini Thomson to be paraphyletic with respect to three other tribes. The genera Suphisellus Crotch and Hydrocanthus Say are also recovered as paraphyletic. Following the results of the preferred partitioning scheme, we here propose a revised classification of Noteridae, comprising two subfamilies, three tribes and 18 genera. The following taxonomic changes are made: Notomicrinae sensu n. (= Phreatodytinae syn. n.) is expanded to include the tribe Phreatodytini; Noterini sensu n. (= Neohydrocoptini syn. n., Pronoterini syn. n., Tonerini syn. n.) is expanded to include all genera of the Noterinae; The genus Suphisellus Crotch is expanded to include species of Pronoterus Sharp syn. n.; and the former subgenus Sternocanthus Guignot stat. rev. is resurrected from synonymy and elevated to genus rank. Copyright © 2016 Elsevier Inc. All rights reserved.

Responses of Cerambycidae and Other Insects to Traps Baited With Ethanol, 2,3-Hexanediol, and 3,2-Hydroxyketone Lures in North-Central Georgia.

PubMed

Miller, D R; Crowe, C M; Mayo, P D; Silk, P J; Sweeney, J D

2015-10-01

In north-central Georgia, 13 species of woodboring beetles (Coleoptera: Cerambycidae: Cerambycinae) were attracted to multiple-funnel traps baited with ethanol and one of the following pheromones: (1) racemic 3-hydroxyhexan-2-one; (2) racemic 3-hydroxyoctan-2-one; and (3) syn-2,3-hexanediol. The following species were attracted to traps baited with ethanol and 3-hydroxyhexan-2-one: Anelaphus pumilus (Newman), Eburia quadrigeminata (Say), Euderces pini (Olivier), Knulliana cincta (Drury), Neoclytus mucronatus (F.), Neoclytus scutellaris (Olivier), and Xylotrechus colonus (F.). Clytus marginicollis Castelnau & Gory, and Anelaphus parallelus (Newman) were attracted to traps baited with ethanol and 3-hydroxyoctan-2-one, whereas traps baited with ethanol and syn-2,3-hexanediol were attractive to Anelaphus villosus (F.), A. parallelus, Neoclytus acuminatus (F.), Neoclytus jouteli jouteli Davis, and Megacyllene caryae (Gahan). Ethanol enhanced catches of seven cerambycid species in traps baited with syn-2,3-hexanediol and 3,2-hydroxyketones. Catches of bark and ambrosia beetles (Curculionidae: Scolytinae) in ethanol-baited traps were largely unaffected by the addition of syn-2,3-hexanediol and 3,2-hydroxyketone lures, except for two species. The mean catches of Hypothenemus rotundicollis Wood & Bright and Dryoxylon onoharaensum (Murayama) in ethanol-baited traps increased and decreased, respectively, with the addition of racemic 3-hydroxyoctan-2-one. Traps baited with ethanol and syn-2,3-hexanediol were attractive to Xylobiops basilaris (Say) (Bostrichidae) and Chariessa pilosa (Forster) (Cleridae), whereas Temnoscheila virescens (F.) (Trogossitidae) were attracted to traps baited with ethanol and 3-hydroxyhexan-2-one. The assassin bug, Apiomerus crassipes (F.) (Hemiptera: Reduviidae), was attracted to traps baited with ethanol and 3,2-hydroxyketones. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.

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.

A survey of gastrointestinal parasites of alpacas (Vicugna pacos) raised in Japan

PubMed Central

HYUGA, Ayako; MATSUMOTO, Jun

2015-01-01

This study aimed to determine the prevalence of gastrointestinal parasites in alpacas raised in Japan. From December 2010 to October 2011, 53 alpacas (Vicugna pacos) raised at a farm in the Kanto region, Japan, were examined for gastrointestinal parasites by 3 fecal tests: direct smear, centrifuged flotation and formalin-ether sedimentation. Eggs of Nematodirus sp. were found in 13.2%, Trichuris sp. in 11.3%, Capillaria spp. in 5.7%, strongyle-type in 50.9% and Moniezia sp. in 1.9%. Oocysts of Eimeria punoensis and/or E. alpacae were found in 69.8%, E. lamae in 1.9% and E. macusaniensis in 7.5%. We found that alpacas raised in Japan have gastrointestinal parasitic fauna similar to those in other countries. PMID:26725443

Parasitological survey on birds at some selected brazilian zoos.

PubMed

Hofstatter, Paulo Gonzalez; Guaraldo, Ana Maria Aparecida

2015-01-01

A parasitological survey was conducted at some zoos in the states of São Paulo and Paraná, Brazil, from 2009 to 2011. Several groups of birds were surveyed for fecal samples, but the most important was Psittacidae. Among the parasites, Eimeria (coccidian) and Capillaria, Ascaridia and Heterakis (nematodes) were observed in almost one third of the samples. Presence of a rich parasite fauna associated with captive birds seems to be an effect of captivity, since data on free-ranging birds indicate few or virtually no parasites at all. The discovery of new coccidian species during this survey reveals the need of more research on the subject as even well-known bird species have unknown parasites, but caution must be exercised in order to avoid descriptions of pseudoparasites.

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.

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.

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.

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.

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...

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.

Reassessment of Paleotachina Townsend and Electrotachina Townsend and their removal from the Tachinidae (Diptera).

PubMed

O'Hara, James E; Raper, Christopher M; Pont, Adrian C; Whitmore, Daniel

2013-01-01

The monotypic genera Paleotachina Townsend, 1921 and Electrotachina Townsend, 1938 were originally described as fossils in amber but were later discovered to be inclusions in copal. Both taxa were originally assigned to the Tachinidae (Diptera) and this placement has continued to the present day. The holotypes of the two type species, P. smithii Townsend and E. smithii Townsend, were examined and the following taxonomic and nomenclatural changes are proposed: Paleotachina is transferred to the Muscidae and placed in synonymy with Aethiopomyia Malloch, 1921, syn. n.; P. smithii Townsend, type species of Paleotachina, is synonymized with Aethiopomyia gigas (Stein, 1906), syn. n.; Electrotachina is transferred to the Sarcophagidae and placed in synonymy with Dolichotachina Villeneuve, 1913, syn. n.; E. smithii Townsend, type species of Electrotachina, is recognized as a valid species of Dolichotachina comb. n. Images of the holotypes of P. smithii and E. smithii are provided and features that have helped place these copal inclusions in their new combinations are discussed.

Priority and synonymy of some North American cicada genera (Hemiptera: Cicadidae: Cicadinae: Cryptotympanini).

PubMed

Sanborn, Allen F; Heath, Maxine S

2017-03-15

The status of several North American cicada genera is reconsidered based on the recent erection of new genera and historical evidence. Megatibicen Sanborn & Heath, 2016 is shown to have priority over Megatibicen Lee, 2016 (which was changed by the author to Gigatibicen Lee, 2016 prior to formal publication). Ameritibicen Lee, 2016 is shown to be a junior synonym of Megatibicen Sanborn & Heath, 2016 and both Ameritibicen n. syn. and and Gigatibicen Lee, 2016 n. syn. are synonymized here to Megatibicen Sanborn & Heath. The species placed in Gigatibicen are returned to Megatibicen to become Megatibicen auletes (Germar, 1834) n. comb., Megatibicen resh (Haldeman, 1852) n. comb., and Megatibicen resonans (Walker, 1850) n. comb. while the species placed in Ameritibicen remain in Megatibicen due to the junior synonym status of Ameritibicen. The monospecific Paratibicen Lee, 2016 n. syn. is shown to be a junior synonym of Neotibicen Hill & Marshall, 2015 and its species is reassigned to Neotibicen to become Neotibicen similaris (Smith & Grossbeck, 1907) n. comb.

Theoretical study of the thermodynamics of the mechanisms underlying antiradical activity of cinnamic acid derivatives.

PubMed

Amić, Ana; Marković, Zoran; Klein, Erik; Dimitrić Marković, Jasmina M; Milenković, Dejan

2018-04-25

The role of antiradical moieties (catechol, guaiacyl and carboxyl group) and molecular conformation in antioxidative potency of dihydrocaffeic acid (DHCA) and dihydroferulic acid (DHFA) was investigated by density functional theory (DFT) method. The thermodynamic preference of different reaction paths of double (2H + /2e - ) free radical scavenging mechanisms was estimated. Antiradical potency of DHCA and DHFA was compared with that exerted by their unsaturated analogs - caffeic acid (CA) and ferulic acid (FA). Cis/trans and anti-isomers of studied cinnamic acid derivatives may scavenge free radicals via double processes by involvement of catechol or guaiacyl moiety. Carboxyl group of syn-isomers may also participate in the inactivation of free radicals. Gibbs free energies of reactions with various free radicals indicate that syn-DHCA and syn-DHFA, colon catabolites that could be present in systemic circulation in low μM concentrations, have a potential to contribute to health benefits by direct free radical scavenging. Copyright © 2017 Elsevier Ltd. All rights reserved.

Geraniol attenuates α-synuclein expression and neuromuscular impairment through increase dopamine content in MPTP intoxicated mice by dose dependent manner.

PubMed

Rekha, Karamkolly R; Selvakumar, Govindasamy P; Santha, Karunanithi; Inmozhi Sivakamasundari, Ramu

2013-11-01

Parkinson's disease (PD) is characterized by progressive loss of dopamine (DA) neurons in the nigrostriatal system and by the presence of Lewy bodies (LB), proteinaceous inclusions mainly composed of filamentous α-synuclein (α-Syn) aggregates. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was adopted to generate PD models in C57BL/6 mice. In the present study, we investigated the effect of geraniol (GE) against α-Syn aggregation on MPTP induced mouse model of PD in dose dependant manner. When pretreatment of GE improved neuromuscular impairment, TH expressions and decreases α-Syn expressions in MPTP intoxicated PD mice by dose dependent manner. In addition, we confirmed that sub-chronic administration of MPTP in mice leads to permanent neuromuscular deficits and depletion of dopamine and its metabolites. Our results suggest that GE is beneficial for the treatment of PD associated with neuromuscular disability and LB aggregation. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

A novel and facile decay path of Criegee intermediates by intramolecular insertion reactions via roaming transition states

NASA Astrophysics Data System (ADS)

Nguyen, Trong-Nghia; Putikam, Raghunath; Lin, M. C.

2015-03-01

We have discovered a new and highly competitive product channel in the unimolecular decay process for small Criegee intermediates, CH2OO and anti/syn-CH3C(H)OO, occurring by intramolecular insertion reactions via a roaming-like transition state (TS) based on quantum-chemical calculations. Our results show that in the decomposition of CH2OO and anti-CH3C(H)OO, the predominant paths directly produce cis-HC(O)OH and syn-CH3C(O)OH acids with >110 kcal/mol exothermicities via loose roaming-like insertion TSs involving the terminal O atom and the neighboring C-H bonds. For syn-CH3C(H)OO, the major decomposition channel occurs by abstraction of a H atom from the CH3 group by the terminal O atom producing CH2C(H)O-OH. At 298 K, the intramolecular insertion process in CH2OO was found to be 600 times faster than the commonly assumed ring-closing reaction.

Multiple cell adhesion molecules shaping a complex nicotinic synapse on neurons.

PubMed

Triana-Baltzer, Gallen B; Liu, Zhaoping; Gounko, Natalia V; Berg, Darwin K

2008-09-01

Neuroligin, SynCAM, and L1-CAM are cell adhesion molecules with synaptogenic roles in glutamatergic pathways. We show here that SynCAM is expressed in the chick ciliary ganglion, embedded in a nicotinic pathway, and, as shown previously for neuroligin and L1-CAM, acts transcellularly to promote synaptic maturation on the neurons in culture. Moreover, we show that electroporation of chick embryos with dominant negative constructs disrupting any of the three molecules in vivo reduces the total amount of presynaptic SV2 overlaying the neurons expressing the constructs. Only disruption of L1-CAM and neuroligin, however, reduces the number of SV2 puncta specifically overlaying nicotinic receptor clusters. Disrupting L1-CAM and neuroligin together produces no additional decrement, indicating that they act on the same subset of synapses. SynCAM may affect synaptic maturation rather than synapse formation. The results indicate that individual neurons can express multiple synaptogenic molecules with different effects on the same class of nicotinic synapses.

Millimeter and submillimeter wave spectroscopy of propanal

NASA Astrophysics Data System (ADS)

Zingsheim, Oliver; Müller, Holger S. P.; Lewen, Frank; Jørgensen, Jes K.; Schlemmer, Stephan

2017-12-01

The rotational spectra of the two stable conformers syn- and gauche-propanal (CH3CH2CHO) were studied in the millimeter and submillimeter wave regions from 75 to 500 GHz with the Cologne (Sub-)Millimeter wave Spectrometer. Furthermore, the first excited states associated with the aldehyde torsion and with the methyl torsion, respectively, of the syn-conformer were analyzed. The newly obtained spectroscopic parameters yield better predictions, thus fulfill sensitivity and resolution requirements in new astronomical observations in order to unambiguously assign pure rotational transitions of propanal. This is demonstrated on a radio astronomical spectrum from the Atacama Large Millimeter/submillimeter Array Protostellar Interferometric Line Survey (ALMA-PILS). In particular, an accurate description of observed splittings, caused by internal rotation of the methyl group in the syn-conformer and by tunneling rotation interaction from two stable degenerate gauche-conformers, is reported. The rotational spectrum of propanal is of additional interest because of its two large amplitude motions pertaining to the methyl and the aldehyde group, respectively.

Valproic acid ameliorates C. elegans dopaminergic neurodegeneration with implications for ERK-MAPK signaling.

PubMed

Kautu, Bwarenaba B; Carrasquilla, Alejandro; Hicks, Matthew L; Caldwell, Kim A; Caldwell, Guy A

2013-04-29

Parkinson's disease (PD) is a currently incurable neurodegenerative disorder that affects the aging population. The loss of dopaminergic neurons in the substantia nigra is one of the pathological features of PD. The precise causes of PD remain unresolved but evidence supports both environmental and genetic contributions. Current efforts for the treatment of PD are directed toward the discovery of compounds that show promise in impeding age-dependent neurodegeneration in PD patients. Alpha-synuclein (α-Syn) is a human protein that is mutated in specific populations of patients with familial PD. Overexpression of α-Syn in animal models of PD replicates key symptoms of PD, including neurodegeneration. Here, we use the nematode Caenorhabditis elegans as a model system, whereby α-Syn toxicity causes dopaminergic neurodegeneration, to test the capacity of valproic acid (VA) to protect neurons. The results of our study showed that treatment of nematodes with moderate concentrations of VA significantly protects dopaminergic neurons against α-Syn toxicity. Consistent with previously established knowledge related to the mechanistic action of VA in the cell, we showed through genetic analysis that the neuroprotection conferred by VA is inhibited by cell-specific depletion of the C. elegans ortholog of the MAP extracellular signal-regulated kinase (ERK), MPK-1, in the dopaminergic neurons. These findings suggest that VA may exert its neuroprotective effect via ERK-MAPK, or alternately could act with MAPK signaling to additively provide dopaminergic neuroprotection. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Retinal is formed from apo-carotenoids in Nostoc sp. PCC7120: in vitro characterization of an apo-carotenoid oxygenase

PubMed Central

Scherzinger, Daniel; Ruch, Sandra; Kloer, Daniel P.; Wilde, Annegret; Al-Babili, Salim

2006-01-01

The sensory rhodopsin from Anabaena (Nostoc) sp. PCC7120 is the first cyanobacterial retinylidene protein identified. Here, we report on NosACO (Nostoc apo-carotenoid oxygenase), encoded by the ORF (open reading frame) all4284, as the candidate responsible for the formation of the required chromophore, retinal. In contrast with the enzymes from animals, NosACO converts β-apo-carotenals instead of β-carotene into retinal in vitro. The identity of the enzymatic products was proven by HPLC and gas chromatography–MS. NosACO exhibits a wide substrate specificity with respect to chain lengths and functional end-groups, converting β-apo-carotenals, (3R)-3-hydroxy-β-apo-carotenals and the corresponding alcohols into retinal and (3R)-3-hydroxyretinal respectively. However, kinetic analyses revealed very divergent Km and Vmax values. On the basis of the crystal structure of SynACO (Synechocystis sp. PCC6803 apo-carotenoid oxygenase), a related enzyme showing similar enzymatic activity, we designed a homology model of the native NosACO. The deduced structure explains the absence of β-carotene-cleavage activity and indicates that NosACO is a monotopic membrane protein. Accordingly, NosACO could be readily reconstituted into liposomes. To localize SynACO in vivo, a Synechocystis knock-out strain was generated expressing SynACO as the sole carotenoid oxygenase. Western-blot analyses showed that the main portion of SynACO occurred in a membrane-bound form. PMID:16759173

Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin derivative.

PubMed

Walker, Leslie; Perkins, Eddie; Kratz, Felix; Raucher, Drazen

2012-10-15

Elastin-like polypeptide (ELP) is a macromolecular carrier with thermally responsive properties that can passively accumulate in solid tumors and additionally aggregate in tumor tissue when exposed to hyperthermia. In this study, ELP was conjugated to the anticancer drug doxorubicin (DOXO) and three different cell penetrating peptides (CPP) in order to inhibit tumor growth in mice compared to free doxorubicin. Fluorescence microscopy studies in MCF-7 breast carcinoma cells demonstrated that the three different CPP-ELP-DOXO conjugates delivered doxorubicin to the cell nucleus. All CPP-ELP-DOXO conjugates showed cytotoxicity with IC(50) values in the range of 12-30 μM at 42 °C, but the ELP carrier with SynB1 as the cell penetrating peptide had the lowest intrinsic cytotoxicity. Therefore, the antitumor efficacy of SynB1-ELP-DOXO was compared to doxorubicin under hyperthermic conditions. C57BL/6 female mice bearing syngeneic E0771 murine breast tumors were treated with either free doxorubicin or the SynB1-ELP-DOXO conjugate with or without focused hyperthermia on the tumor. Under hyperthermic conditions, tumor inhibition with SynB1-ELP-DOXO was 2-fold higher than under therapy with free doxorubicin at the equivalent dose, and is thus a promising lead candidate for optimizing thermally responsive drug polymer conjugates. Copyright © 2012 Elsevier B.V. All rights reserved.

Systematics of the east Palaearctic pear psyllids (Hemiptera: Psylloidea) with particular focus on the Japanese and Korean fauna.

PubMed

Cho, Geonho; Burckhardt, Daniel; Inoue, Hiromitsu; Luo, Xinyu; Lee, Seunghwan

2017-12-04

The confused taxonomy of the east Palaearctic pear psyllids, serious pests on cultivated pear, is reviewed. Fifty-six nominal species have been reported from Pyrus, 25 of which we consider valid and ten as not being associated with Pyrus. Our taxonomic revision suggests that, in Korea, four Cacopsylla species develop on pear: the univoltine C. burckhardti Luo et al. previously misidentified as C. pyrisuga (Foerster), the polyvoltine, seasonally dimorphic C. jukyungi (Kwon) (winter form 'cinereosignata' Luo et al., summer form 'jukyungi'), commonly found in Korean pear orchards, and C. maculatili Li (winter form 'maculatili', summer form 'qiuzili' Li) previously misidentified as C. pyricola (Foerster) by some authors, as well as the probably polyvoltine but not dimorphic C. sandolbaea (Park & Lee). The former three species (C. burckhardti, C. jukyungi, misidentified as C. chinensis (Yang & Li), and C. maculatili) occur also in Japan. Keys to the adult and fifth instar immatures as well as short biological notes are provided, and C. jukyungi and C. sandolbaea are redescribed. Following nomenclatorial changes are proposed: Cacopsylla betulaefoliae (Yang & Li, 1981) = Psylla heterobetulaefoliae Yang & Li, 1981, syn. nov.; Cacopsylla bidens (Šulc, 1907) = Psylla jiangli Yang & Li, 1981, syn. nov.; Cacopsylla jukyungi (Kwon) = C. cinereosignata Luo et al., syn. nov.; Cacopsylla maculatili Li = C. qiuzili Li, syn. nov.; Cacopsylla nigella (Konovalova), comb. nov. from Psylla. The synonymy of P. obongsana Kwon with C. sandolbaea is confirmed.

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.