Dengue virus receptor

Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essential for an understanding of dengue pathology. In addition, understanding the molecular mechanism(s) of virus entry is crucial for the development of effective new therapies to treat dengue patients. Binding of dengue virus to its receptor molecules is mediated through a viral envelope glycoprotein, termed E protein. We present a summary and describe the structures, binding properties, and pathological relevance of dengue virus receptor molecules proposed to date. In mammalian cells, there are many candidate molecules that may act as receptors, such as sulfated glycosaminoglycans (GAGs), lectins that recognize carbohydrates, glycosphingolipid (GSL), proteins with chaperone activity, laminin-binding proteins, and other uncharacterized proteins. There are also several lines of evidence for receptor molecules such as GSLs, proteins with chaperone activity, laminin-binding proteins, and other uncharacterized proteins in mosquito cells and organs. This review focuses on several molecules involved in carbohydrate-dependent binding of the virus

A unique biosynthetic pathway for gangliosides exists in Xenopus laevis oocytes

AbstractIt was previously reported that monosialosylgangliopentaosyl ceramide (Ga1NAc-GM1b) was a major ganglioside in Xenopus laevis oocytes. Here we determined biosynthetic pathways for the ganglioside by detailed measurements of glycosyltransferase activities. CMP-NeuAc:asialo-GM1 α2–3 sialyltransferase (α2–3 ST) and UDP-Ga1NAc:GM1b β1–4 N-acetylgalactosaminyltransferase (β1–4 Ga1NAcT) exhibited much higher activity than CMP-NeuAc:Ga1NAc-GA1 α2–3 ST and UDP-Ga1NAc:asialo-GM1 β1–4 Ga1NAcT, respectively. These observations indicated the existence of a unique biosynthetic pathway in the oocytes as follows; asialo-GM1 → GM1b → Ga1NAc-GM1b

CSP alpha reduces aggregates and rescues striatal dopamine release in alpha-synuclein transgenic mice

alpha-Synuclein aggregation at the synapse is an early event in Parkinson's disease and is associated with impaired striatal synaptic function and dopaminergic neuronal death. The cysteine string protein (CSP alpha) and alpha-synuclein have partially overlapping roles in maintaining synaptic function and mutations in each cause neurodegenerative diseases. CSP alpha is a member of the DNAJ/HSP40 family of co-chaperones and like alpha-synuclein, chaperones the SNARE complex assembly and controls neurotransmitter release. alpha-Synuclein can rescue neurodegeneration in CSP alpha KO mice. However, whether alpha-synuclein aggregation alters CSP alpha expression and function is unknown. Here we show that alpha-synuclein aggregation at the synapse is associated with a decrease in synaptic CSP alpha and a reduction in the complexes that CSP alpha forms with HSC70 and STG alpha. We further show that viral delivery of CSP alpha rescues in uitro the impaired vesicle recycling in PC12 cells with alpha-synuclein aggregates and in uiuo reduces synaptic alpha-synuclein aggregates increasing monomeric alpha-synuclein and restoring normal dopamine release in 1-120h alpha Syn mice. These novel findings reveal a mechanism by which alpha-synuclein aggregation alters CSP alpha at the synapse, and show that CSP alpha rescues alpha-synuclein aggregation-related phenotype in 1-120h alpha Syn mice similar to the effect of alpha-synuclein in CSP alpha KO mice. These results implicate CSP alpha as a potential therapeutic target for the treatment of earlystage Parkinson's disease

In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease

Both the replication of protein aggregates and their spreading throughout the brain are implicated in the progression of Alzheimer’s disease (AD). However, the rates of these processes are unknown and the identity of the rate-determining process in humans has therefore remained elusive. By bringing together chemical kinetics with measurements of tau seeds and aggregates across brain regions, we can quantify their replication rate in human brains. Notably, we obtain comparable rates in several different datasets, with five different methods of tau quantification, from postmortem seed amplification assays to tau PET studies in living individuals. Our results suggest that from Braak stage III onward, local replication, rather than spreading between brain regions, is the main process controlling the overall rate of accumulation of tau in neocortical regions. The number of seeds doubles only every ∼5 years. Thus, limiting local replication likely constitutes the most promising strategy to control tau accumulation during AD

The Effect of Aromatherapy by Lavender Oil on Infant Vaccination Pain: a Double Blind Randomized Controlled Trial

Introduction: Exposure to noxious stimuli can cause pain in infants. This study was conducted to evaluate the effects of the lavender oil inhalation on the pain resulting from the pentavalent vaccination. Methods: This clinical trial consisted of two groups: the lavender oil group with 42 infants and the placebo group with 57 infants. The healthy infants without congenital abnormalities in need of pentavalent vaccine also participated in our study. The infants started the lavender oil or placebo aromatherapy one minute before injection. The pain was assessed three times, using the Neonatal Infant pain Scale (NIPS): before vaccination, 15 s, and 5 min after vaccination. Also, the duration of crying was measured in both groups. Results: At baseline, the two groups were similar in relation to the NIPS scores. While, after 5 minutes, the NIPS score was significantly lower in the lavender group. Based on the repeated measures analysis, the NIPS score changed over time totally. However, the two groups were significantly different in relation to the NIPS score over time. The duration of crying was 75.47 (60.675) second in the lavender group and 105.22 (75.739) s in the control group. The statistical test showed a significant difference between the two groups. Conclusion: A low concentration of the lavender oil inhalation can reduce the pain and improve soothing in the infants with the pentavalent vaccine injection

Alpha Synuclein only Forms Fibrils In Vitro when Larger than its Critical Size of 70 Monomers

Funder: UK Dementia Research Institute; Id: http://dx.doi.org/10.13039/501100017510Funder: DRI Ltd.Funder: UK Medical Research CouncilFunder: Alzheimer's SocietyFunder: Alzheimer's Research UKFunder: Royal Society; Id: http://dx.doi.org/10.13039/501100000288Funder: Herchel Smith Postdoctoral Research FellowshipAbstract: The aggregation of α‐synuclein into small soluble aggregates and then fibrils is important in the development and spreading of aggregates through the brain in Parkinson's disease. Fibrillar aggregates can grow by monomer addition and then break into fragments that could spread into neighboring cells. The rate constants for fibril elongation and fragmentation have been measured but it is not known how large an aggregate needs to be before fibril formation is thermodynamically favorable. This critical size is an important parameter controlling at what stage in an aggregation reaction fibrils can form and replicate. We determined this value to be approximately 70 monomers using super‐resolution and atomic force microscopy imaging of individual α‐synuclein aggregates formed in solution over long time periods. This represents the minimum size for a stable α‐synuclein fibril and we hypothesis the formation of aggregates of this size in a cell represents a tipping point at which rapid replication occurs

In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease.

[Figure: see text].We acknowledge funding from Sidney Sussex College Cambridge (GM) and the European Research Council Grant Number 669237 (to D.K.) and the Royal Society (to D.K.). The Cambridge Brain Bank is supported by the NIHR Cambridge Biomedical Research Centre

Silkworm expression system as a platform technology in life science

Many recombinant proteins have been successfully produced in silkworm larvae or pupae and used for academic and industrial purposes. Several recombinant proteins produced by silkworms have already been commercialized. However, construction of a recombinant baculovirus containing a gene of interest requires tedious and troublesome steps and takes a long time (3–6 months). The recent development of a bacmid, Escherichia coli and Bombyx mori shuttle vector, has eliminated the conventional tedious procedures required to identify and isolate recombinant viruses. Several technical improvements, including a cysteine protease or chitinase deletion bacmid and chaperone-assisted expression and coexpression, have led to significantly increased protein yields and reduced costs for large-scale production. Terminal N-acetyl glucosamine and galactose residues were found in the N-glycan structures produced by silkworms, which are different from those generated by insect cells. Genomic elucidation of silkworm has opened a new chapter in utilization of silkworm. Transgenic silkworm technology provides a stable production of recombinant protein. Baculovirus surface display expression is one of the low-cost approaches toward silkworm larvae-derived recombinant subunit vaccines. The expression of pharmaceutically relevant proteins, including cell/viral surface proteins, membrane proteins, and guanine nucleotide-binding protein (G protein) coupled receptors, using silkworm larvae or cocoons has become very attractive. Silkworm biotechnology is an innovative and easy approach to achieve high protein expression levels and is a very promising platform technology in the field of life science. Like the “Silkroad,” we expect that the “Bioroad” from Asia to Europe will be established by the silkworm expression system