by Mari Kajiwara Saito, Christopher M. Parry, Shunmay Yeung

Typhoid fever is a common cause of fever in Cambodian children but diagnosis and treatment are usually presumptive owing to the lack of quick and accurate tests at an initial consultation. This study aimed to evaluate the cost-effectiveness of using a rapid diagnostic test (RDT) for typhoid fever diagnosis, an immunoglobulin M lateral flow assay (IgMFA), in a remote health centre setting in (altro…)

by Yvonne Ukamaka Ajamma, Thomas Ogao Onchuru, Daniel O. Ouso, David Omondi, Daniel K. Masiga, Jandouwe Villinger

Background

Many arboviruses transmitted by mosquitoes have been implicated as causative agents of both human and animal illnesses in East Africa. Although epidemics of arboviral emerging infectious diseases have risen in frequency in recent years, the extent to which mosquitoes maintain pathogens in circulation during inter-epidemic periods is still poorly understood. This study aimed to (altro…)

by Tie-Long Xu, Yin Han, Wei Liu, Xing-Ya Pang, Bin Zheng, Yi Zhang, Xiao-Nong Zhou

Background

Dengue fever is the most rapidly spreading mosquito-borne viral disease over the past 50 years, with a 30-fold increase in global incidence. Dengue vector control is a key component for the dengue control strategy, since no absolutely effective vaccine or drug is available yet. However, the rapid rise and spread of mosquito insecticide resistance have become (altro…)

by Letícia B. Smith, Rakshit Tyagi, Shinji Kasai, Jeffrey G. Scott

Aedes aegypti poses a serious risk to human health due to its wide global distribution, high vector competence for several arboviruses, frequent human biting, and ability to thrive in urban environments. Pyrethroid insecticides remain the primary means of controlling adult A. aegypti populations during disease outbreaks. As a result of decades of use, pyrethroid resistance is a global problem. Cytochrome P450 (altro…)

by Jared P. May, Xuefeng Yuan, Erika Sawicki, Anne E. Simon

Nonsense-mediated decay (NMD) is a host RNA control pathway that removes aberrant transcripts with long 3’ untranslated regions (UTRs) due to premature termination codons (PTCs) that arise through mutation or defective splicing. To maximize coding potential, RNA viruses often contain internally located stop codons that should also be prime targets for NMD. Using an agroinfiltration-based NMD assay in Nicotiana benthamiana, we (altro…)

by Qian Shen, Matthew J. Beucler, Stephanie C. Ray, Chad A. Rappleye

Copper toxicity and copper limitation can both be effective host defense mechanisms against pathogens. Tolerance of high copper by fungi makes toxicity as a defense mechanism largely ineffective against fungal pathogens. A forward genetic screen for Histoplasma capsulatum mutant yeasts unable to replicate within macrophages showed the Ctr3 copper transporter is required for intramacrophage proliferation. Ctr3 mediates copper uptake and (altro…)

by Mayuri Gogoi, Kasturi Chandra, Mohsen Sarikhani, Ramya Ramani, Nagalingam Ravi Sundaresan, Dipshikha Chakravortty

Salmonella being a successful pathogen, employs a plethora of immune evasion mechanisms. This contributes to pathogenesis, persistence and also limits the efficacy of available treatment. All these contributing factors call upon for new drug targets against Salmonella. For the first time, we have demonstrated that Salmonella upregulates sirtuin 2 (SIRT2), an NAD⁺ dependent deacetylase in dendritic cells (DC). (altro…)

by Colby L. Samstag, Jake G. Hoekstra, Chiu-Hui Huang, Mark J. Chaisson, Richard J. Youle, Scott R. Kennedy, Leo J. Pallanck

Mitochondrial DNA (mtDNA) mutations cause severe maternally inherited syndromes and the accumulation of somatic mtDNA mutations is implicated in aging and common diseases. However, the mechanisms that influence the frequency and pathogenicity of mtDNA mutations are poorly understood. To address this matter, we created a Drosophila mtDNA mutator strain expressing a (altro…)

by Markus G. Stetter, Kevin Thornton, Jeffrey Ross-Ibarra

Understanding the genetic basis of phenotypic adaptation to changing environments is an essential goal of population and quantitative genetics. While technological advances now allow interrogation of genome-wide genotyping data in large panels, our understanding of the process of polygenic adaptation is still limited. To address this limitation, we use extensive forward-time simulation to explore the impacts of variation in demography, trait genetics, and selection (altro…)

by Yasmin M. Vasquez, Xiaoqiu Wang, Margeaux Wetendorf, Heather L. Franco, Qianxing Mo, Tianyuan Wang, Rainer B. Lanz, Steven L. Young, Bruce A. Lessey, Thomas E. Spencer, John P. Lydon, Francesco J. DeMayo

Successful embryo implantation requires a receptive endometrium. Poor uterine receptivity can account for implantation failure in women who experience recurrent pregnancy loss or multiple rounds of unsuccessful in vitro fertilization cycles. Here, we demonstrate that the transcription factor Forkhead (altro…)

by Fabien Delahaye, Catherine Do, Yu Kong, Remi Ashkar, Martha Salas, Ben Tycko, Ronald Wapner, Francine Hughes

From genomic association studies, quantitative trait loci analysis, and epigenomic mapping, it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression. For this reason, an analysis of the effects of genetic variation on gene expression and DNA methylation in human placentas at high resolution (altro…)

by Maheva Andriatsilavo, Marine Stefanutti, Katarzyna Siudeja, Carolina N. Perdigoto, Benjamin Boumard, Louis Gervais, Alexandre Gillet-Markowska, Lara Al Zouabi, François Schweisguth, Allison J. Bardin

Precise regulation of stem cell self-renewal and differentiation properties is essential for tissue homeostasis. Using the adult Drosophila intestine to study molecular mechanisms controlling stem cell properties, we identify the gene split-ends (spen) in a genetic screen as a novel regulator of intestinal stem cell fate (ISC). Spen (altro…)

by Isaac T. Sluder, Nitika, Laura E. Knighton, Andrew W. Truman

Hsp70 is a well-conserved molecular chaperone involved in the folding, stabilization, and eventual degradation of many “client” proteins. Hsp70 is regulated by a suite of co-chaperone molecules that assist in Hsp70-client interaction and stimulate the intrinsic ATPase activity of Hsp70. While previous studies have shown the anticancer target ribonucleotide reductase (RNR) is a client of Hsp70, the regulatory co-chaperones involved remain (altro…)

by Jaume Bonet, Sarah Wehrle, Karen Schriever, Che Yang, Anne Billet, Fabian Sesterhenn, Andreas Scheck, Freyr Sverrisson, Barbora Veselkova, Sabrina Vollers, Roxanne Lourman, Mélanie Villard, Stéphane Rosset, Thomas Krey, Bruno E. Correia

The robust computational design of functional proteins has the potential to deeply impact translational research and broaden our understanding of the determinants of protein function and stability. The low success rates of computational design protocols and the extensive in vitro (altro…)

by Grant Hartung, Claudia Vesel, Ryan Morley, Ali Alaraj, John Sled, David Kleinfeld, Andreas Linninger

Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling. While the principal mechanisms of blood flow regulation after neuronal firing are generally known, mechanistic hemodynamic simulations cannot yet pinpoint the exact spatial and temporal coordination between the network of arteries, arterioles, capillaries and veins for the (altro…)