Differential unfolded protein response during Chikungunya and Sindbis virus infection: CHIKV nsP4 suppresses eIF2α phosphorylation

10.1186/1743-422X-10-36Virology Journal10

18F-fluorodeoxyglucose positron emission tomography as a window into human dengue pathophysiology.

In mouse models of dengue virus (DENV) infection, 18F-FDG PET is able to sensitively detect tissue-specific sites of inflammation and disease activity, as well as track therapeutic response to anti- DENV agents. However, the use of 18F-FDG PET to study the pathogenesis of inflammation and disease activity in DENV infection in humans, has not been clinically validated. Here we report the 18F-FDG PET imaging results of two patients during the febrile phase of acute DENV infection, paired with serial serum viral load, NS1 and proinflammatory cytokine measurements. Our findings demonstrate that 18F-FDG PET is able to sensitively detect and quantify organ-specific inflammation in the lymph nodes and spleen, in classic acute dengue fever. This raises the potential for 18F-FDG PET to be used as a research tool that may provide further insights into disease pathogenesis

Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models.Kptn−/− mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants.Molecular and structural analysis of Kptn−/− mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1.By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.Genetics of disease, diagnosis and treatmen

Cloning and expression of the exposed portion of the envelop protein of the four dengue virus serotypes

[Extract] Dengue fever is a growing public health concern affecting millions of people during annual epidemics in endemic areas. The symptoms of the disease include acute biphasic fever, rash and general malaise. However, sequential infection by different serotypes of the virus can sometimes result in dengue haemorrhagic fever or dengue shock syndrome, which can be fatal.\ud \ud In the absence of a cure for the disease, the control of dengue virus infection can only be achieved by effective public health measures. There is an urgent need for rapid, specific and easy-to-use dengue viral diagnosis tests in endemic areas. The diagnosis of dengue virus infection relies upon either the detection of viraemia during the first 3-5 days of the illness or by the detection of antibody thereafter. The detection of dengue infection by ELISA is preferred in most clinical laboratories because they are easy to do and large numbers of specimens can be processed. Until recently there has been no commercial ELISA. Most laboratories use in-house tests based on published protocols (Kuno, Gomez and Gubler 1991, Bundo and Igarashi 1985). These tests have used viral antigen derived from cell culture. With a view towards development of serotype specific ELISA tests, we wish to report the cloning of E genes encoding the estramembraneous portions of D1 to D4 and their high level expression using the T7 expression system (Studier et al. 1990). We also report the production of soluble domain of E protein from Dengue 2 in insect cells using recombinant Baculovirus

Expression and immunoaffinity purification of recombinant dengue virus 2 NS1 protein as a cleavable SUMOstar fusion

10.1016/j.pep.2011.11.003Protein Expression and Purification82120-25PEXP

Update on Dengue: Epidemiology, Virus Evolution, Antiviral Drugs, and Vaccine Development

10.1007/s11908-010-0102-7Current Infectious Disease Reports1-

Assessing the Utility of Antivirals for Preventing Maternal-Fetal Transmission of Zika Virus in pregnant mice

https://doi.org/10.1016/j.antiviral.2019.04.013Antiviral Research167104-10

Recent progress in cassava varietal improvement in India

In India cassava breeding is done mainly at the Central Tuber Crops Research Institute (CTCRI) in Trivandrum, as well as in the State Agricultural Universities through the All India Co-ordinating Centres. CTCRI maintains 786 exotic and 848 indigenous accessions of cassava and 8 wild species in its germplasm bank. Coordinating Centres maintain about 280 indigenous accessions. Seedling progenies of 158 and 19 CIAT cassava accessions were screened at the Regional Centre of CTCRI in Bhubaneswar during 1985 and 1990, respectively. High root yields of more than 4 kg/plant were recorded in seedling progenies of CM3426, CM4046 and CM4229. Selection of promising germplasm and hybridization among selected accessions have been the principal strategies in cassava breeding. The most popular eating variety in Kerala, M-4, was introduced from Malaysia in the 1950s. Three high yielding hybrids, H-165, H-226 and H-97 were released in 1971 by CTCRI, of which H-165 and H-226 have become popular in Tamil Nadu for starch production. In 1983, 'Sree Sahya' and 'Sree Vishakam' were released at the national level. 'Sree Prakash' is a short duration cultivar released by CTCRI in 1987. In 1993 the Tamil Nadu Agricultural University released a high yielding, short-duration cultivar, called 'Co-3', which is reported to be tolerant to CMD. Recently, the Kerala Agricultural University also released a short-duration cultivar, called 'Nidhi', which can be harvested in 5 1 /2 - 6 months and has been recommended for paddy fallows of central Kerala. Two high yielding high quality short-duration cultivars, which can be harvested at six months, have been identified from the germplasm of CTCRI and are now being evaluated in advanced yield trials. A study on hybrid vigor in cassava indicated the predominance of non-additive gene action for root yield and yield components, indicating the possibility of exploiting hybrid vigor. Seven elite top-cross selections have been identified with high root yield, starch and dry matter contents and with low HCN content. By successive cycles of recurrent selection among germplasm accessions, the carotene content of roots could be raised significantly. Induction of triploidy has been found to be very effective for the development of high yielding, high starch and high dry matter cassava cultivars. A promising triploid, 2/14, is being considered for release for starch processing. Recently, successful induction of mutation has been reported in M-4. A few useful mutants, having higher root yields (20-25%) and high dry matter and starch contents, have been selected from single node cuttings of gamma-irradiated stakes. Studies on the use of true seed revealed the possibility of enhancing the multiplication rate more than 15 fold compared to the traditional method of vegetative propagation. A few promising seedling families have been identified, which give seedling yields comparable to clonal yields. Cassava mosaic disease is considerably reduced in seedling families

Dengue virus serotype infection specifies the activation of the unfolded protein response

10.1186/1743-422X-4-91Virology Journal49

Glycosylation and high-level secretion of human tumour necrosis factor-beta in recombinant baculovirus-infected insect cells

Biotechnology and Applied Biochemistry183259-273BABI