Gene Knockout Techniques

Publication Title: 
The Journal of Biological Chemistry

ATP-binding cassette transporters play an important role in drug resistance and nutrient transport. In the human malaria parasite Plasmodium falciparum, a homolog of the human p-glycoprotein (PfPgh-1) was shown to be involved in resistance to several drugs. More recently, many transporters were associated with higher IC(50) levels in responses to chloroquine (CQ) and quinine (QN) in field isolates. Subsequent studies, however, could not confirm the associations, although inaccuracy in drug tests in the later studies could contribute to the lack of associations.

Author(s): 
Raj, Dipak Kumar
Mu, Jianbing
Jiang, Hongying
Kabat, Juraj
Singh, Subash
Sullivan, Margery
Fay, Michael P.
McCutchan, Thomas F.
Su, Xin-Zhuan
Publication Title: 
PloS One

BACKGROUND: A liver-derived protein, fetuin-A, was first purified from calf fetal serum in 1944, but its potential role in lethal systemic inflammation was previously unknown. This study aims to delineate the molecular mechanisms underlying the regulation of hepatic fetuin-A expression during lethal systemic inflammation (LSI), and investigated whether alterations of fetuin-A levels affect animal survival, and influence systemic accumulation of a late mediator, HMGB1.

Author(s): 
Li, Wei
Zhu, Shu
Li, Jianhua
Huang, Yan
Zhou, Rongrong
Fan, Xuegong
Yang, Huan
Gong, Xing
Eissa, N. Tony
Jahnen-Dechent, Willi
Wang, Ping
Tracey, Kevin J.
Sama, Andrew E.
Wang, Haichao
Publication Title: 
Gut Microbes

Although commensal microbes have been shown to modulate host immune responses, many of the bacterial factors that mediate immune regulation remain unidentified. Select strains of human-derived Lactobacillus reuteri synthesize immunomodulins that potently inhibit production of the inflammatory cytokine TNF. In this study, genetic and genomic approaches were used to identify and investigate L. reuteri genes required or human TNF immunomodulatory activity. Analysis of membrane fatty acids from multiple L.

Author(s): 
Jones, Sara E.
Whitehead, Kristi
Saulnier, Delphine
Thomas, Carissa M.
Versalovic, James
Britton, Robert A.
Publication Title: 
PloS One

BACKGROUND: Enteroaggregative Escherichia coli (EAEC) is recognized as an emerging cause of persistent diarrhea and enteric disease worldwide. Mucosal immunity towards EAEC infections is incompletely understood due in part to the lack of appropriate animal models. This study presents a new mouse model and investigates the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the modulation of host responses to EAEC in nourished and malnourished mice.

Author(s): 
Philipson, Casandra W.
Bassaganya-Riera, Josep
Viladomiu, Monica
Pedragosa, Mireia
Guerrant, Richard L.
Roche, James K.
Hontecillas, Raquel
Publication Title: 
Molecular Biology of the Cell

AMP-activated protein kinase (AMPK) is a key energy sensor that regulates metabolism to maintain cellular energy balance. AMPK activation has also been proposed to mimic benefits of caloric restriction and exercise. Therefore, identifying downstream AMPK targets could elucidate new mechanisms for maintaining cellular energy homeostasis. We identified the phosphotransferase nucleoside diphosphate kinase (NDPK), which maintains pools of nucleotides, as a direct AMPK target through the use of two-dimensional differential in-gel electrophoresis.

Author(s): 
Onyenwoke, Rob U.
Forsberg, Lawrence J.
Liu, Lucy
Williams, Tyisha
Alzate, Oscar
Brenman, Jay E.
Publication Title: 
Cell Metabolism

We have explored the role of mitochondrial function in aging by genetically and pharmacologically modifying yeast cellular respiration production during the exponential and/or stationary growth phases and determining how this affects chronological life span (CLS). Our results demonstrate that respiration is essential during both growth phases for standard CLS, but that yeast have a large respiratory capacity, and only deficiencies below a threshold (~40% of wild-type) significantly curtail CLS.

Author(s): 
Ocampo, Alejandro
Liu, Jingjing
Schroeder, Elizabeth A.
Shadel, Gerald S.
Barrientos, Antoni
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