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Parasites & Vectors Jun 2024Cache Valley virus (CVV) is an understudied Orthobunyavirus with a high spillover transmission potential due to its wide geographical distribution and large number of...
BACKGROUND
Cache Valley virus (CVV) is an understudied Orthobunyavirus with a high spillover transmission potential due to its wide geographical distribution and large number of associated hosts and vectors. Although CVV is known to be widely distributed throughout North America, no studies have explored its geography or employed computational methods to explore the mammal and mosquito species likely participating in the CVV sylvatic cycle.
METHODS
We used a literature review and online databases to compile locality data for CVV and its potential vectors and hosts. We linked location data points with climatic data via ecological niche modeling to estimate the geographical range of CVV and hotspots of transmission risk. We used background similarity tests to identify likely CVV mosquito vectors and mammal hosts to detect ecological signals from CVV sylvatic transmission.
RESULTS
CVV distribution maps revealed a widespread potential viral occurrence throughout North America. Ecological niche models identified areas with climate, vectors, and hosts suitable to maintain CVV transmission. Our background similarity tests identified Aedes vexans, Culiseta inornata, and Culex tarsalis as the most likely vectors and Odocoileus virginianus (white-tailed deer) as the most likely host sustaining sylvatic transmission.
CONCLUSIONS
CVV has a continental-level, widespread transmission potential. Large areas of North America have suitable climate, vectors, and hosts for CVV emergence, establishment, and spread. We identified geographical hotspots that have no confirmed CVV reports to date and, in view of CVV misdiagnosis or underreporting, can guide future surveillance to specific localities and species.
Topics: Animals; Mosquito Vectors; Ecosystem; North America; Bunyamwera virus; Culicidae; Bunyaviridae Infections; Geography; Culex; Aedes; Mammals; Deer; Humans; Ecology
PubMed: 38926834
DOI: 10.1186/s13071-024-06344-z -
Scientific Reports Jun 2024Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations...
Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations are situated in the last exon and we previously demonstrated escape from nonsense-mediated decay by detecting mutant ADNP mRNA in patient blood. In this study, wild-type and ADNP mutants are investigated at the protein level and therefore optimal detection of the protein is required. Detection of ADNP by means of western blotting has been ambiguous with reported antibodies resulting in non-specific bands without unique ADNP signal. Validation of an N-terminal ADNP antibody (Aviva Systems) using a blocking peptide competition assay allowed to differentiate between specific and non-specific signals in different sample materials, resulting in a unique band signal around 150 kDa for ADNP, above its theoretical molecular weight of 124 kDa. Detection with different C-terminal antibodies confirmed the signals at an observed molecular weight of 150 kDa. Our antibody panel was subsequently tested by immunoblotting, comparing parental and homozygous CRISPR/Cas9 endonuclease-mediated Adnp knockout cell lines and showed disappearance of the 150 kDa signal, indicative for intact ADNP. By means of both a GFPSpark and Flag-tag N-terminally fused to a human ADNP expression vector, we detected wild-type ADNP together with mutant forms after introduction of patient mutations in E. coli expression systems by site-directed mutagenesis. Furthermore, we were also able to visualize endogenous ADNP with our C-terminal antibody panel in heterozygous cell lines carrying ADNP patient mutations, while the truncated ADNP mutants could only be detected with epitope-tag-specific antibodies, suggesting that addition of an epitope-tag possibly helps stabilizing the protein. However, western blotting of patient-derived hiPSCs, immortalized lymphoblastoid cell lines and post-mortem patient brain material failed to detect a native mutant ADNP protein. In addition, an N-terminal immunoprecipitation-competent ADNP antibody enriched truncating mutants in overexpression lysates, whereas implementation of the same method failed to enrich a possible native mutant protein in immortalized patient-derived lymphoblastoid cell lines. This study aims to shape awareness for critical assessment of mutant ADNP protein analysis in Helsmoortel-Van der Aa syndrome.
Topics: Humans; Homeodomain Proteins; Nerve Tissue Proteins; Mutation; HEK293 Cells; Autism Spectrum Disorder; Heart Diseases; Facies; Neurodevelopmental Disorders
PubMed: 38926592
DOI: 10.1038/s41598-024-65608-x -
Scientific Reports Jun 2024To analyse the genetic aetiology of a child with oculocutaneous albinism and to explore the effects of two mutation sites on the function of the OCA2 protein at the mRNA...
To analyse the genetic aetiology of a child with oculocutaneous albinism and to explore the effects of two mutation sites on the function of the OCA2 protein at the mRNA and protein levels via the use of recombinant carriers in vitro. Whole-exome sequencing (WES) and Sanger sequencing were used to analyse the pathogenic genes of the child and validate the mutations in the parents. pEGFP and phage vectors carrying wild-type and mutant OCA2 were constructed using the coding DNA sequence (CDS) of the whole gene-synthesized OCA2 as a template and transfected into HEK293T cells, after which expression analysis was performed. The child in this study was born with white skin, hair, eyelashes, and eyebrows and exhibited nystagmus. Genetic analysis indicated that the child carried two heterozygous mutations: c.1079C > T (p.Ser360Phe) of maternal origin and c.1095_1103delAGCACTGGC (p.Ala366_Ala368del) of paternal origin, conforming to an autosomal recessive inheritance pattern. In vitro analysis showed that the expression of the c.1079C > T (p.Ser360Phe) mutant did not significantly change at the mRNA level but did increase at the protein level, suggesting that the mutation may lead to enhanced protein stability, and the c.1095_1103delAGCACTGGC (p.Ala366_Ala368del) mutation resulted in the loss of three amino acids in exon 10, producing a truncated protein. In vitro expression analysis also revealed that the expression of the mutant gene was significantly downregulated at both the mRNA and protein levels, suggesting that the mutation can simultaneously produce truncated proteins and lead to protein degradation. This case study enriches the phenotypic spectrum of OCA2 gene disease. In vitro expression analysis confirmed that both mutations affect protein expression, providing a theoretical basis for analysing the pathogenicity of these two mutations.
Topics: Humans; HEK293 Cells; Mutation; Albinism, Oculocutaneous; Membrane Transport Proteins; Exome Sequencing; Female; Male; Pedigree; RNA, Messenger
PubMed: 38926510
DOI: 10.1038/s41598-024-64782-2 -
Plant Biotechnology Journal Jun 2024The development of plant virus-based expression systems has expanded rapidly owing to their potential applications in gene functional and disease resistance research,...
The development of plant virus-based expression systems has expanded rapidly owing to their potential applications in gene functional and disease resistance research, and industrial production of pharmaceutical proteins. However, the low yield of certain proteins, especially high-molecular-mass proteins, restricts the production scale. In this study, we observed that the tobacco mosaic virus (TMV)-mediated expression of a foreign protein was correlated with the amount of the movement protein (MP) and developed a TMV-derived pAT-MP vector system incorporating trans-complementation expression of MP. The system is capable of efficient expression of exogenous proteins, in particular those with a high molecular mass, and enables simultaneous expression of two target molecules. Furthermore, viral expression of competent CRISPR-Cas9 protein and construction of CRISPR-Cas9-mediated gene-editing system in a single pAT-MP construct was achieved. The results demonstrated a novel role for TMV-MP in enhancing the accumulation of a foreign protein produced from the viral vector or a binary expression system. Further investigation of the mechanism underlying this role will be beneficial for optimization of plant viral vectors with broad applications.
PubMed: 38923265
DOI: 10.1111/pbi.14418 -
Journal of Vector Borne Diseases Apr 2024Leishmaniasis is caused by various species of parasite Leishmania. Approximately twenty of them are pathogenic to mammals. In Sri Lanka, cutaneous leishmaniasis (CL) is...
BACKGROUND OBJECTIVES
Leishmaniasis is caused by various species of parasite Leishmania. Approximately twenty of them are pathogenic to mammals. In Sri Lanka, cutaneous leishmaniasis (CL) is an established vector-borne disease. CL originates and spreads mainly through sandfly bite in many endemic countries. The aim of the present study was to compare the geographical distribution and demographic features of CL cases in Hambantota district, Sri Lanka in 2014 and 2016.
METHODS
The patients who were presented to the Tangalle Base Hospital from June to December in 2014 and 2016 were examined and a descriptive study was carried out using a structured-questionnaire. Slit-skin smears were collected from each patient, Giemsa-stained and examined under the light microscope to identify Leishmania amastigotes.
RESULTS
Out of 256 and 314 suspected CL patients, 156 and 155 were identified positive for the year 2014 and 2016, respectively. Out of 12 District Secretary Divisions (DSD) in Hambantota district, the highest number of CL cases, 85 and 86 was reported from Tangalle DSD in 2014 and 2016 respectively. Number of identified CL patients in Beliatta DSD had increased from 50 to 67 during the study period. In both years, majority of CL patients were ≥50 years old with males more infected than females. Although CL association with occupations were insignificant, housewives were the highly (23%) infected occupants in this area.
INTERPRETATION CONCLUSION
Based on the present findings, geographical distribution within DSDs in Hambantota district had changed. This emphasizes the importance of CL as a health problem in Hambantota district.
Topics: Leishmaniasis, Cutaneous; Humans; Sri Lanka; Male; Female; Middle Aged; Adult; Adolescent; Young Adult; Child; Aged; Child, Preschool; Leishmania; Animals; Surveys and Questionnaires; Aged, 80 and over; Psychodidae; Infant
PubMed: 38922662
DOI: 10.4103/jvbd.jvbd_117_23 -
Journal of Vector Borne Diseases Apr 2024Vector-borne haemoprotozoan diseases comprise diverse group of single celled organism transmitted by haematophagus invertebrates. The current study was aimed at the...
BACKGROUND OBJECTIVES
Vector-borne haemoprotozoan diseases comprise diverse group of single celled organism transmitted by haematophagus invertebrates. The current study was aimed at the identification of major haemoprotozoan (Babesia, Theileria and Trypanosoma) in dromedary camel of North Gujarat region in India using microscopy and Polymerase Chain Reaction (PCR).
METHODS
A total of 234 blood samples were screened by the microscopic and molecular detection assays. Molecular prevalence studies of Theileria, Trypanosoma spp and Babesia was undertaken using 18s ribosomal DNA, RoTat 1.2 and SS rRNA gene respectively. The data relating to microscopic and molecular prevalence along with associated risk factors were analysed by statistical methods.
RESULTS
The overall prevalence of hamoprotozoan disease based on microscopic and molecular investigation was 23.50%. The sensitivity and specificity (95% Confidence Interval) of PCR assay was 100% in comparison to microscopy (45.45 % sensitive and 100 % specific). The kappa coefficient between PCR and microscopy indicated good level of agreement with a value of 0.704 and SE of 0.159.
INTERPRETATION CONCLUSION
Despite holding much significance to the animal sector, little work has been undertaken in regional parts of India regarding camel parasites. The present study offers first preliminary research data investigating haemoprotozoan disease using parasitological and molecular methods in camels in the region.
Topics: Animals; Camelus; India; Polymerase Chain Reaction; Microscopy; Trypanosoma; Theileria; Babesia; Theileriasis; RNA, Ribosomal, 18S; DNA, Protozoan; Babesiosis; Prevalence; Male; Sensitivity and Specificity; Trypanosomiasis; Female; Vector Borne Diseases; DNA, Ribosomal
PubMed: 38922661
DOI: 10.4103/jvbd.jvbd_105_23 -
Journal of Vector Borne Diseases Apr 2024Vector-borne infectious diseases contribute significantly to global mortality, with over 700,000 annual deaths, and malaria alone accounts for more than 400,000 of these...
BACKGROUND OBJECTIVES
Vector-borne infectious diseases contribute significantly to global mortality, with over 700,000 annual deaths, and malaria alone accounts for more than 400,000 of these fatalities. Anopheles gambiae, a prominent mosquito species, serves as a primary vector for transmitting malaria to humans. To address this issue, researchers have identified the D1-like dopamine receptor (DAR), specifically DOP2, as a promising target for developing new insecticides.
METHODS
The three-dimensional structure of DOP2 from A. gambiae was unavailable; in-silico approach was used to model and validate DOP2 structure. The Discovery Studio 2021 program was used to identify potential binding sites on DOP2. Virtual screening of 235 anti-parasitic compounds was performed against DOP2 using PyRx 0.8.
RESULTS
The screening demonstrated strong binding and interactions with active site residues of DOP2 for five compounds: Diclazuril, Kaempferol, Deracoxib, Clindamycin, and Diaveridine. These compounds exhibited higher binding affinity values compared to the control (Asenapine). In addition, the predicted physiochemical properties for these compounds were within acceptable ranges and there were no violations in drug-likeness properties.
INTERPRETATION CONCLUSION
These compounds show promise as potential new insecticides targeting A. gambiae mosquito by inhibiting the DOP2 protein. However, additional experimental validation is required to optimize their efficacy as DOP2 inhibitors.
Topics: Animals; Anopheles; Insecticides; Malaria; Mosquito Vectors; Molecular Docking Simulation; Receptors, Dopamine D2; Humans; Binding Sites
PubMed: 38922660
DOI: 10.4103/jvbd.jvbd_158_23 -
Journal of Vector Borne Diseases Apr 2024The range of Aedes albopictus, the most important vector mosquito in Western Eurasia is growing due to climate change. However, it is not known how it will influence the...
BACKGROUND OBJECTIVES
The range of Aedes albopictus, the most important vector mosquito in Western Eurasia is growing due to climate change. However, it is not known how it will influence the habitats occupied by the species and its environmental fitness within its future range.
METHODS
To study this question, the habitat characteristic of the mosquito was investigated for 2081-2100.
RESULTS
The models suggest a notable future spread of the mosquito in the direction of Northern Europe and the parallel northward and westward shift of the southern and eastern potential occurrences of the mosquito. The models suggest a notable increase in generation numbers in the warmest quarter, which can reach 4-5 generations in the peri-Mediterranean region. However, both the joint survival rate of larvae and pupae and the number of survival days of adults in the warmest quarter exhibit decreasing values, as does the potential disappearance of the mosquito in the southern regions of Europe and Asia Minor, along with the growing atmospheric CO2 concentration-based scenarios.
INTERPRETATION CONCLUSION
While in 1970-2000 Aedes albopictus mainly occupied the hot and warm summer temperate regions of Europe, the species will inhabit dominantly the cool summer temperate (oceanic) and the humid continental climate territories of North and North-Eastern Europe in 2081-2100.
Topics: Aedes; Animals; Ecosystem; Europe; Climate Change; Asia; Mosquito Vectors; Larva; Pupa; Seasons
PubMed: 38922659
DOI: 10.4103/jvbd.jvbd_143_23 -
Journal of Vector Borne Diseases Apr 2024Sandflies are vector insects associated with terrestrial forest ecosystems; in the Ecuadorian Andes, they participate in the transmission of human cutaneous...
BACKGROUND OBJECTIVES
Sandflies are vector insects associated with terrestrial forest ecosystems; in the Ecuadorian Andes, they participate in the transmission of human cutaneous leishmaniasis. This geographical area represents an opportunity to evaluate the role of sandflies as bioindicators of the degree of intervention of tropical humid forest ecosystems (THF) associated with changes in the ecology of the local landscape.
METHODS
CDC-light traps were used for collecting adult sandflies in February 2020 in a humid tropical forest within the Chocó Biosphere Reserve. All species were identified using morphological keys. Analysis data about abundance, richness, species accumulation, diversity index, species composition communities, species sex proportion, spatial sandflies environmental, Renyi's Diversity Profile were performed to compare six spatial habitats in Mashpi locality, Ecuador.
RESULTS
Sandflies were collected (n-1435); the main species are represented by Trichophoromyia reburra, Nyssomyia trapidoi, Psathyromyia aclydifera, Psychodopygus panamensis and Lutzomyia hartmanni. Only Th. reburra is associated with not intervened forest, while the other three species are associated with intervened forest within Mashpi in the Choco Biosphere Reserve. The secondary forest has major sandflies' richness, while the primary forest exhibits major abundance.
INTERPRETATION CONCLUSION
Th. reburra is a sandfly restricted to the Andean Forest and is a bioindicator of the high environmental health quality of the forest, while Ny. trapidoi and Pa. aclydifera are bioindicators of environmental disturbances in the forest. Additionally, Ps. panamensis, Lu. hartmanni and Ny. trapidoi are bioindicators of human impact and the risk of leishmaniasis.
Topics: Animals; Psychodidae; Forests; Insect Vectors; Ecuador; Ecosystem; Male; Female; Leishmaniasis, Cutaneous; Biodiversity; Humans
PubMed: 38922658
DOI: 10.4103/jvbd.jvbd_52_23 -
Journal of Vector Borne Diseases Apr 2024Aedes aegypti and Ae. albopictus mosquitoes breed in natural and artificial containers, and they transmit dengue and chikungunya. A study was conducted to identify the...
BACKGROUND OBJECTIVES
Aedes aegypti and Ae. albopictus mosquitoes breed in natural and artificial containers, and they transmit dengue and chikungunya. A study was conducted to identify the contribution of bamboo stumps to these disease vectors that were used in the flower garden as pillars to hold the bamboo flex fence.
METHODS
Two sizes of whole bamboo were used to hold fences around gardens at Dhaka University, Bangladesh, and were painted red and green. Mosquito larvae and pupae were collected from bamboo stumps between July and August, and vectors were identified up to the species level. The data were analyzed using the STATA/MP 14.2 version.
RESULTS
83.5% and 0.2% were Ae. albopictus and Ae. aegypti, respectively, and the remaining were Culex and Ar-migeres species. Ae. albopictus, Ae. aegypti, and both species-positive bamboo stumps were 46.9, 0.7, and 47.1%, respectively. 54.5% of the bamboo stumps had at least one mosquito species. The average stump depth for Aedes positive stumps (mean=11.7 cm, SE = 0.5) was significantly (p <0.001) higher than the Aedes negative stumps (mean = 9.5 cm, SE = 0.4). 53.8% and 38.0% stumps were found Aedes positive on the ground and upper sides of fences, respectively, and found significant (p<0.01) differences between both sides. A zero-inflated negative binomial count model is significant at a 5% level of significance, χ2(4) = 11.8, p = 0.019 (<0.05) for Ae. albopictus. Stump depth is found to have a significant positive effect on the number of Aedes-positive stumps.
INTERPRETATION CONCLUSION
Artificially used natural containers are adding pressure to current mosquito control activities as mosquitoes are breeding on them, which needs additional attention.
Topics: Animals; Bangladesh; Dengue; Aedes; Mosquito Control; Mosquito Vectors; Chikungunya Fever; Larva; Pupa; Sasa; Culex; Humans
PubMed: 38922657
DOI: 10.4103/jvbd.jvbd_152_23