排序方式: 共有75条查询结果,搜索用时 15 毫秒
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Baye Ashenefe Wassie Surafel Fantaw Yonas Mekonene Amete Mihret Teshale Yohannis Yitagesu Estifanos Tsige Desalegn Getahun Geremew Tasew Getachew Abichu Beyene Moges Ebba Abate Takele Abayneh Taye Zeru Zewdu Belay Siobhan M. Mor 《PLoS neglected tropical diseases》2022,16(2)
BackgroundAnthrax is a disease that affects humans and animals. In Ethiopia, anthrax is a reportable disease and assumed to be endemic, although laboratory confirmation has not been routinely performed until recently. We describe the findings from the investigation of two outbreaks in Amhara region.MethodsFollowing reports of suspected outbreaks in Wag Hamra zone (Outbreak 1) and South Gondar zone (Outbreak 2), multi-sectoral teams involving both animal and public health officials were deployed to investigate and establish control programs. A suspect case was defined as: sudden death with rapid bloating or bleeding from orifice(s) with unclotted blood (animals); and signs compatible with cutaneous, ingestion, or inhalation anthrax ≤7 days after exposure to a suspect animal (humans). Suspect human cases were interviewed using a standard questionnaire. Samples were collected from humans with suspected anthrax (Outbreak 1 and Outbreak 2) as well as dried meat of suspect animal cases (Outbreak 2). A case was confirmed if a positive test was returned using real-time polymerase chain reaction (qPCR).ResultsIn Outbreak 1, a total of 49 cows died due to suspected anthrax and 22 humans developed symptoms consistent with cutaneous anthrax (40% attack rate), two of whom died due to suspected ingestion anthrax. Three people were confirmed to have anthrax by qPCR. In Outbreak 2, anthrax was suspected to have caused the deaths of two livestock animals and one human. Subsequent investigation revealed 18 suspected cases of cutaneous anthrax in humans (27% attack rate). None of the 12 human samples collected tested positive, however, a swab taken from the dried meat of one animal case (goat) was positive by qPCR.ConclusionWe report the first qPCR-confirmed outbreaks of anthrax in Ethiopia. Both outbreaks were controlled through active case finding, carcass management, ring vaccination of livestock, training of health professionals and outreach with livestock owners. Human and animal health authorities should work together using a One Health approach to improve case reporting and vaccine coverage. 相似文献
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Ebba Gregorsson Lundius Nikolas Stroth Vladana Vukojević Lars Terenius Per Svenningsson 《Journal of neurochemistry》2013,124(3):410-417
G protein‐coupled receptor 37 (GPR37) is suggested to be implicated in the pathogenesis of Parkinson's disease and is accumulating in Lewy bodies within afflicted brain regions. Over‐expressed GPR37 is prone to misfolding and aggregation, causing cell death via endoplasmic reticulum stress. Although the cytotoxicity of misfolded GPR37 is well established, effects of the functional receptor on cell viability are still unknown. An N2a cell line stably expressing green fluorescent protein (GFP)‐tagged human GPR37 was created to study its trafficking and effects on cell viability upon challenge with the toxins 1‐methyl‐4‐phenylpyridinium (MPP+), rotenone and 6‐hydroxydopamine (6‐OHDA). Neuronal‐like differentiation into a tyrosine hydroxylase expressing phenotype, using dibutyryl‐cAMP, induced trafficking of GPR37 to the plasma membrane. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) cell viability and lactate dehydrogenase (LDH) cell death assays revealed that GPR37 was protective against all three toxins in differentiated cells. In undifferentiated cells, the majority of GPR37 was cytoplasmic and the protective effects were more variable: GPR37 expression protected against rotenone and MPP+ but not against 6‐OHDA in MTT assays, while it protected against 6‐OHDA but not against MPP+ or rotenone in lactate dehydrogenase (LDH) assays. These results suggest that GPR37 functionally trafficked to the plasma membrane protects against toxicity. 相似文献
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Shanie Saghafian-Hedengren Ebba Sohlberg Jakob Theorell Claudia Carvalho-Queiroz Noémi Nagy Jan-Olov Persson Caroline Nilsson Yenan T. Bryceson Eva Sverremark-Ekstr?m 《Journal of virology》2013,87(24):13446-13455
During childhood, infections with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) can occur in close temporal proximity. Active, as well as latent, CMV infection is associated with enlarged subsets of differentiated natural killer (NK) and cytotoxic T cells. How EBV infection may influence CMV-driven immune differentiation is not known. We found that EBV coinfection selectively influenced the NK cell compartment of CMV-seropositive (CMV+) children. Coinfected children had significantly higher proportions of peripheral-blood NKG2C+ NK cells than CMV+ EBV− children. Ex vivo NK cell degranulation after target cell stimulation and plasma IL-15 levels were significantly higher in CMV+ children. EBV coinfection was related to the highest levels of plasma interleukin-15 (IL-15) and IL-12p70. Remarkably, in vitro EBV infection of peripheral blood mononuclear cells (PBMC) from EBV− CMV+ children increased NKG2C+ NK cell proportions. A similar tendency was seen in cocultures of PBMC with EBV+ lymphoblastoid B-cell lines (LCL) and IL-15. After K562 challenge, NKG2C+ NK cells excelled in regard to degranulation and production of gamma interferon, regardless of whether there was previous coculture with LCL. Taken together, our data suggest that dual latency with these herpesviruses during childhood could contribute to an in vivo environment supporting differentiation and maintenance of distinct NK cell populations. This viral imprint may affect subsequent immune responses through altered distributions of effector cells. 相似文献
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Guven Gamze Bilgic Basar Samanci Bedia Gurvit Hakan Hanagasi Hasmet Donmez Cagla Aslan Rukiye Lohmann Ebba Erginel-Unaltuna Nihan 《Molecular biology reports》2020,47(8):5903-5909
Molecular Biology Reports - ‘Triggering receptor expressed on myeloid cells 2’ (TREM2) gene is involved in Alzheimer’s disease (AD) and TREM2 mRNA expression is known to be... 相似文献
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Three proteins, intrinsic factor (IF), transcobalamin (TC), and haptocorrin (HC), all have an extremely high affinity for the cobalamins (Cbls, Kd approximately 5 fM) but discriminate these physiological ligands from Cbl analogues with different efficiencies decreasing in the following order: IF > TC > HC. We investigated interactions of these proteins with a number of ligands: Cbl, fluorescent conjugate CBC, two base-off analogues [pseudo-coenzyme B12 (pB) and adenosyl factor A (fA)], and a baseless corrinoid cobinamide. Protein-ligand encounter and the following internal rearrangements in both molecules were registered as a change in the fluorescence of CBC (alone or mixed with other ligands), a transition in absorbance of pB and fA (base-off --> on-base conversion), and alterations in the molecular mass of two split IF domains. The greater complexity of the binding kinetics followed better Cbl specificity (HC < TC < IF). On the basis of the experimental results, we propose a general binding model with three major steps: (1) initial attachment of the ligand to the high-affinity C-domain, (2) primary assembly of N- and C-domains, and (3) slow adjustments and fixation of the ligand at the domain-domain interface. Since step 3 was characteristic of highly specific TC and especially IF, we suggest its particular importance for ligand recognition. The designed models revealed the absolute Kd values for a group of analogues. Calculations show that most of them could potentially bind to the specific transporters IF and TC under physiological conditions. Implications of this finding and the protective role of HC are discussed. 相似文献
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Niccolo E. Mencacci Ignacio Rubio-Agusti Anselm Zdebik Friedrich Asmus Marthe H.R. Ludtmann Mina Ryten Vincent Plagnol Ann-Kathrin Hauser Sara Bandres-Ciga Conceição Bettencourt Paola Forabosco Deborah Hughes Marc M.P. Soutar Kathryn Peall Huw R. Morris Daniah Trabzuni Mehmet Tekman Horia C. Stanescu Robert Kleta Miryam Carecchio Giovanna Zorzi Nardo Nardocci Barbara Garavaglia Ebba Lohmann Anne Weissbach Christine Klein John Hardy Alan M. Pittman Thomas Foltynie Andrey Y. Abramov Thomas Gasser Kailash P. Bhatia Nicholas W. Wood 《American journal of human genetics》2015,96(6):938-947
Myoclonus-dystonia (M-D) is a rare movement disorder characterized by a combination of non-epileptic myoclonic jerks and dystonia. SGCE mutations represent a major cause for familial M-D being responsible for 30%–50% of cases. After excluding SGCE mutations, we identified through a combination of linkage analysis and whole-exome sequencing KCTD17 c.434 G>A p.(Arg145His) as the only segregating variant in a dominant British pedigree with seven subjects affected by M-D. A subsequent screening in a cohort of M-D cases without mutations in SGCE revealed the same KCTD17 variant in a German family. The clinical presentation of the KCTD17-mutated cases was distinct from the phenotype usually observed in M-D due to SGCE mutations. All cases initially presented with mild myoclonus affecting the upper limbs. Dystonia showed a progressive course, with increasing severity of symptoms and spreading from the cranio-cervical region to other sites. KCTD17 is abundantly expressed in all brain regions with the highest expression in the putamen. Weighted gene co-expression network analysis, based on mRNA expression profile of brain samples from neuropathologically healthy individuals, showed that KCTD17 is part of a putamen gene network, which is significantly enriched for dystonia genes. Functional annotation of the network showed an over-representation of genes involved in post-synaptic dopaminergic transmission. Functional studies in mutation bearing fibroblasts demonstrated abnormalities in endoplasmic reticulum-dependent calcium signaling. In conclusion, we demonstrate that the KCTD17 c.434 G>A p.(Arg145His) mutation causes autosomal dominant M-D. Further functional studies are warranted to further characterize the nature of KCTD17 contribution to the molecular pathogenesis of M-D. 相似文献
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Ebba Gregorsson Lundius Vladana Vukojevi? Ellen Hertz Nikolas Stroth Andreas Cederlund Masao Hiraiwa Lars Terenius Per Svenningsson 《The Journal of biological chemistry》2014,289(8):4660-4673
The subcellular distribution of the G protein-coupled receptor GPR37 affects cell viability and is implicated in the pathogenesis of parkinsonism. Intracellular accumulation and aggregation of GPR37 cause cell death, whereas GPR37 located in the plasma membrane provides cell protection. We define here a pathway through which the recently identified natural ligand, prosaposin, promotes plasma membrane association of GPR37. Immunoabsorption of extracellular prosaposin reduced GPR37tGFP surface density and decreased cell viability in catecholaminergic N2a cells. We found that GPR37tGFP partitioned in GM1 ganglioside-containing lipid rafts in the plasma membrane of live cells. This partitioning required extracellular prosaposin and was disrupted by lipid raft perturbation using methyl-β-cyclodextrin or cholesterol oxidase. Moreover, complex formation between GPR37tGFP and the GM1 marker cholera toxin was observed in the plasma membrane. These data show functional association between GPR37, prosaposin, and GM1 in the plasma membrane. These results thus tie together the three previously defined components of the cellular response to insult. Our findings identify a mechanism through which the receptor''s natural ligand and GM1 may protect against toxic intracellular GPR37 aggregates observed in parkinsonism. 相似文献
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Haptocorrin (HC) is a circulating corrinoid binding protein with unclear function. In contrast to transcobalamin, the other transport protein in blood, HC is heavily glycosylated and binds a variety of cobalamin (Cbl) analogues. HC is present not only in blood but also in various secretions like milk, tears and saliva. No recombinant form of HC has been described so far. We report the expression of recombinant human HC (rhHC) in human embryonic kidney cells. We purified the protein with a yield of 6 mg (90 nmol) per litre of cell culture supernatant. The isolated rhHC behaved as native HC concerning its spectral properties and ability to recognize both Cbl and its baseless analogue cobinamide. Similar to native HC isolated from blood, rhHC bound to the asialoglycoprotein receptor only after removal of terminal sialic acid residues by treatment with neuraminidase. Interestingly, rhHC, that compared to native HC contains four excessive amino acids (…LVPR) at the C-terminus, showed subtle changes in the binding kinetics of Cbl, cobinamide and the fluorescent Cbl conjugate CBC. The recombinant protein has properties very similar to native HC and although showing slightly different ligand binding kinetics, rhHC is valuable for further biochemical and structural studies. 相似文献
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