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Jacob Giehm Mikkelsen
Following the successful development of virus-based gene vehicles for genetic therapies, exploitation of viruses as carriers of genetic tools for cellular reprogramming and genome editing should be right up the street. However, whereas persistent, potentially life-long gene expression is the main goal of conventional genetic therapies, tools and bits for genome engineering should ideally be short-lived and active only for a limited time. Although viral vector systems have already been adapted for potent genome editing both in vitro and in vivo, regulatable gene expression systems or self-limiting expression circuits need to be implemented limiting exposure of chromatin to genome-modifying enzymes...
June 18, 2018: Current Opinion in Genetics & Development
Alireza Salimi Chirani, Mona Ghazi, Mehdi Goudarzi, Shahin Najar Peerayeh, Hoorieh Soleimanjahi, Masoud Dadashi, Bahareh Hajikhani
Helicobacter pylori (H. pylori) as microaerophilic, Gram-negative bacterium colonize the human gastric milieu, where it impetuses chronic disorders. Vaccination is a complementary plan, along with antibiotic therapy, for clearance of H. pylori. Today, Computer based tools are essential for the evaluation, design, and experiment for novel chimeric targets for immunological administration. The purpose of this experiment was immunoinformatic analysis of UreB and HpaA molecules in a fusion arrangement and also, construction and expression of recombinant protein containing chimeric sequences...
May 5, 2018: Computational Biology and Chemistry
Natalí Álvarez, Giovan F Gómez, Nelson Naranjo-Díaz, Margarita M Correa
The Arribalzagia Series of the Anopheles Subgenus comprises morphologically similar species or members of species complexes which makes correct species identification difficult. Therefore, the aim of this work was to discriminate the morphospecies of the Arribalzagia Series present in Colombia using a multilocus approach based on ITS2, COI and CAD sequences. Specimens of the Arribalzagia Series collected at 32 localities in nine departments were allocated to seven species. Individual and concatenated Bayesian analyses showed high support for each of the species and reinforced the previous report of the Apicimacula species Complex with distribution in the Pacific Coast and northwestern Colombia...
June 18, 2018: Infection, Genetics and Evolution
Liwen Cui, Xiaolei Xie, Zuojun Shen
There have been rapidly growing applications using machine learning models for predictive analytics in Electronic Health Records (EHR) to improve the quality of hospital services and the efficiency of healthcare resource utilization. A fundamental and crucial step in developing such models is to convert medical codes in EHR to feature vectors. These medical codes are used to represent diagnoses or procedures. Their vector representations have a tremendous impact on the performance of machine learning models...
June 18, 2018: Journal of Biomedical Informatics
Ding Kai, Liao Yannian, Chen Yitian, Gong Dinghao, Zhao Xin, Ji Wu
Recent studies have implied that circHIPK3, an abundant circular RNA (circRNA), participates in tumorigenesis and cancer progression. Its expression and potential functions in human gallbladder cancer were examined in this study. We show that circHIPK3 is upregulated in human gallbladder cancer cells. But its level is low in gallbladder epithelial cells. circHIPK3 silencing by targeted siRNA potently inhibited survival and proliferation of established and primary human gallbladder cancer cells, while inducing cell apoptosis...
June 18, 2018: Biochemical and Biophysical Research Communications
Pauline van den Driessche
This primer article focuses on the basic reproduction number, <mml:math xmlns:mml=""> <mml:mrow> <mml:msub> <mml:mi>ℛ</mml:mi> <mml:mn>0</mml:mn> </mml:msub> </mml:mrow> </mml:math> , for infectious diseases, and other reproduction numbers related to <mml:math xmlns:mml=""> <mml:mrow> <mml:msub> <mml:mi>ℛ</mml:mi> <mml:mn>0</mml:mn> </mml:msub> </mml:mrow> </mml:math> that are useful in guiding control strategies...
August 2017: Infectious Disease Modelling
Jiasen Xie, Zishan Zhou, Shunchang Jiao, Xiaokun Li
A chimeric antigen receptor (CAR) is a type of fusion protein that comprises an antigen-recognition domain and signaling domains. In the present study, a programmed death-ligand 1 (PD-L1)-specific CAR, comprised of a single-chain variable fragment (scFv) derived from a monoclonal antibody, co-stimulatory domains of cluster of differentiation (CD) 28 and 4-1BB and a T-cell-activation domain derived from CD3ζ, was designed. The construction was cloned and packaged into the lentiviral vector pLVX. Flow cytometry confirmed that peripheral blood mononuclear cells were efficiently transduced and that the CAR was successfully expressed on T cells...
July 2018: Oncology Letters
Tai Ping Zhao, Xin Liang Wang, Yi Min Han
The aim of the study was to investigate possible effects of p57 on the growth of the human MCF-7 and rat SHZ-88 breast cancer cell lines. Specific oligonucleotide sequences containing small hairpin structure were inserted into a small interfering RNA (siRNA) expression vector. The human MCF-7 and rat SHZ-88 breast cancer cell lines were transfected with recombinant plasmids. The p57 gene expression was blocked in the human MCF-7 breast and rat SHZ-88 breast cancer cells, using chemically modified siRNA. The p57 expression level was evaluated using quantitative polymerase chain reaction (qPCR) and western blot analysis...
July 2018: Oncology Letters
Shuhui Hong, Xiaoyan Li, Ying Zhao, Qifeng Yang, Beihua Kong
The major problems faced during the treatment of ovarian cancer are metastasis and the development of intrinsic or acquired drug resistance. The present study assessed whether tumor protein p53 binding protein 1 (53BP1) regulated migration and modulated chemotherapy resistance in SKOV3 cells and identified proteins associated with the molecular mechanisms underlying this coordinate regulation. SKOV3 cells were transfected using a 53BP1-expressing vector, which induced 53BP1 overexpression. The migration of the transfected cells was observed using a Transwell assay...
June 2018: Oncology Letters
Tam T Tran, Lizanne Janssens, Khuong V Dinh, Robby Stoks
While transgenerational plasticity may buffer ectotherms to warming and pesticides separately, it remains unknown how combined exposure to warming and pesticides in the parental generation shapes the vulnerability to these stressors in the offspring. We studied the transgenerational effects of single and combined exposure to warming (4°C increase) and the pesticide chlorpyrifos on life-history traits of the vector mosquito Culex pipiens . Parental exposure to a single stressor, either warming or the pesticide, had negative effects on the offspring: parental exposure to both warming and the pesticide resulted in an overall lower offspring survival, and a delayed offspring metamorphosis...
July 2018: Evolutionary Applications
Daniel Stukenberg, Stefan Zauner, Gianluca Dell'Aquila, Uwe G Maier
CRISPR/Cas9 is a powerful tool for genome editing. We constructed an easy-to-handle expression vector for application in the model organism Phaeodactylum tricornutum and tested its capabilities in order to apply CRISPR/Cas9 technology for our purpose. In our experiments, we targeted two different genes, screened for mutations and analyzed mutated diatoms in a three-step process. In the end, we identified cells, showing either monoallelic or homo-biallelic targeted mutations. Thus, we confirm that application of the CRISPR/Cas9 system for P...
2018: Frontiers in Plant Science
Kishor Kumar Paul, Parnali Dhar-Chowdhury, C Emdad Haque, Hasan Mohammad Al-Amin, Doli Rani Goswami, Mohammad Abdullah Heel Kafi, Michael A Drebot, L Robbin Lindsay, Gias Uddin Ahsan, W Abdullah Brooks
Dengue viruses are responsible for over 100 million infections a year worldwide and are a public health concern in Bangladesh. Although risk of transmission is high, data on vector population characteristics are scanty in Bangladesh; therefore, a comprehensive prediction of the patterns of local virus transmission is not possible. Recognizing these gaps, multi-year entomological surveys were carried out in Dhaka, where the disease is most frequently reported. The specific objectives of the present study are threefold: i) to determine the risk factors for the presence of Aedes mosquitoes; ii) to identify the types of most productive and key containers; and iii) to estimate the effects of climatic factors on Aedes abundance in the city of Dhaka, Bangladesh...
2018: PloS One
Evan Kesinger, Jianing Liu, Aaron Jensen, Catherine P Chia, Andrew Demers, Hideaki Moriyama
BACKGROUND: A new type of influenza virus, known as type D, has recently been identified in cattle and pigs. Influenza D virus infection in cattle is typically asymptomatic; however, its infection in swine can result in clinical disease. Swine can also be infected with all other types of influenza viruses, namely A, B, and C. Consequently, swine can serve as a "mixing vessel" for highly pathogenic influenza viruses, including those with zoonotic potential. Currently, the only antiviral drug available targets influenza M2 protein ion channel is not completely effective...
2018: PloS One
A Fuentes, W E Braswell, R Ruiz-Arce, A Racelis
Citrus greening disease, or huanglongbing (HLB), is currently one of the most devastating diseases of citrus. The bacteria thought to be responsible for the disease, Candidatus Liberibacter asiaticus impact the majority of commercial citrus species worldwide. These bacteria are transmitted by the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, which is now found in most citrus growing regions. With no known cure, ACP-vectored HLB is responsible for significant economic losses to the global citrus industry...
2018: PloS One
Bradley J Main, Jay Nicholson, Olivia C Winokur, Cody Steiner, Kasen K Riemersma, Jackson Stuart, Ryan Takeshita, Michelle Krasnec, Christopher M Barker, Lark L Coffey
Zika virus (ZIKV) has emerged since 2013 as a significant global human health threat following outbreaks in the Pacific Islands and rapid spread throughout South and Central America. Severe congenital and neurological sequelae have been linked to ZIKV infections. Assessing the ability of common mosquito species to transmit ZIKV and characterizing variation in mosquito transmission of different ZIKV strains is important for estimating regional outbreak potential and for prioritizing local mosquito control strategies for Aedes and Culex species...
June 2018: PLoS Neglected Tropical Diseases
Gurvinder Kaur, Lea Ann Thompson, Rachel L Babcock, Karl Mueller, Jannette M Dufour
Long-term survival of allo- and xenotransplanted immune-privileged Sertoli cells (SCs) is well documented suggesting that SCs can be used to deliver foreign proteins for cell-based gene therapy. The aim of this study was to use a lentivirus carrying proinsulin cDNA to achieve stable expression and lowering of blood glucose levels (BGLs). A SC line transduced with the lentivirus (MSC-LV-mI) maintained stable insulin expression in vitro. These MSC-LV-mI cells were transplanted and grafts were analyzed for cell survival, continued proinsulin mRNA, and insulin protein expression...
June 21, 2018: DNA and Cell Biology
Matthew L Danielson, Geri A Sawada, Thomas J Raub, Prashant V Desai
The organic anion-transporting polypeptide 1B1 transporter belongs to the solute carrier superfamily and is highly expressed at the basolateral membrane of hepatocytes. Several clinical studies showed drug-drug interactions involving OATP1B1 thereby prompting the International Transporter Consortium to label OATP1B1 as a critical transporter that can influence a compound's disposition. To examine OATP1B1 inhibition early in the drug discovery process, we established a medium-throughput concentration-dependent OATP1B1 assay...
June 21, 2018: Molecular Pharmaceutics
Joshua M Lubner, Jeremy L Balsbaugh, George M Church, Michael F Chou, Daniel Schwartz
Characterizing protein kinase substrate specificity motifs represents a powerful step in elucidating kinase-signaling cascades. The protocol described here uses a bacterial system to evaluate kinase specificity motifs in vivo, without the need for radioactive ATP. The human kinase of interest is cloned into a heterologous bacterial expression vector and allowed to phosphorylate E. coli proteins in vivo, consistent with its endogenous substrate preferences. The cells are lysed, and the bacterial proteins are digested into peptides and phosphoenriched using bulk TiO2 ...
June 2018: Current Protocols in Chemical Biology
Ying Xie, Xiao Han, Yansong Miao
The expression and purification of recombinant proteins using bacterial vectors is a mature and preferred system to obtain folded and stable proteins. However, functional post-translational protein modifications, such as glycosylation or phosphorylation, can only be achieved using eukaryotic expression systems. In addition, insolubility is another challenge when using proteins expressed in Escherichia coli, such as certain intrinsically disordered proteins, which are more prone to aggregation than folded proteins...
June 5, 2018: Current Protocols in Molecular Biology
J A Amadi, G O Ong'amo, D O Olago, S O Oriaso, I K Nyamongo, B B A Estambale
Anopheles gambiae s.l. (Diptera: Culicidae) is responsible for the transmission of the devastating Plasmodium falciparum (Haemosporida: Plasmodiidae) strain of malaria in Africa. This study investigated the relationship between climate and environmental conditions and An. gambiae s.l. larvae abundance and modelled the larval distribution of this species in Baringo County, Kenya. Mosquito larvae were collected using a 350-mL dipper and a pipette once per month from December 2015 to December 2016. A random forest algorithm was used to generate vegetation cover classes...
June 21, 2018: Medical and Veterinary Entomology
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