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Gut delivery of Orsay virus capsid proteins induces longevity and hyperactive behavior in Caenorhabditis elegans
Priyanka Mishra, Lilly Hueber, Megan Cornall, Sheliza Shivji, Victoria Kooner, Michelle Mony, Brandon Kong, Aaron Chang, Zina Aburegeba, Laure Etzi, Alekesy Bikov, Frederic Pio.
Mitochondrial respiratory chain composition and organization in response to changing oxygen levels
Alba Timón-Gómez and Antoni Barrientos
Engineering polymersomes for intracellular biopharmaceutics delivery
Min Qiu and Chao Deng
Cell size dependent migration of T-cells latently infected with HIV
Kathrin Bohn-Wippert and Roy D. Dar
Glutamine diet supplementation prevents obesity through inhibiting inflammation
Ying Yang
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Lakshanie Carmen Wickramasinghe and Jessica Geraldine Borger
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Michelle A. Linterman
Combining immune checkpoint blockade with ErbB targeted therapies for cancer treatment
Zhida Liu, Chuanhui Han, Yang-Xin Fu
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Divya Bhatia, Mary E. Choi
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Rosa-Maria Ferraiuolo, Kay-Uwe Wagner
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Author(s)
Priyanka Mishra, Lilly Hueber, Megan Cornall, Sheliza Shivji, Victoria Kooner, Michelle Mony, Brandon Kong, Aaron Chang, Zina Aburegeba, Laure Etzi, Alekesy Bikov, Frederic Pio.

Institute
Simon Fraser University, Canada
Address

Molecular Biology and Biochemistry Department,Simon Fraser University, British Columbia, Ca V5A1S6, Canada.


Abstract:

Caenorhabditis elegans infection by Orsay virus initiates a variety of abnormalities, including intestinal damages. However, the role of the viral capsid proteins to this pathogenicity needs to be further discovered. To address this question, engineered bacterial lawn expressing recombinant viral proteins were used as a food source to deliver them to the worm gut, and survival and behavioral studies by assessing worm mobility were performed. Worm fed with protein α-δ and δ survived longer while δ contributes to worm intestinal defects. Morphological analysis suggests that protein α limits food absorption in the intestine while α-δ plays a role in food digestion. Moreover, experiments tracking worm mobility showed hyperactive behavior by more forward and less reverse movement, as well as less time pausing. It shows that capsid proteins promote an adaptive behavioral response to food ingestion and locomotion. Since hyperactivity has been previously linked to serotonin by others, the viral protein may modulate the serotonin level in the worm gut. These data are consistent with comparative modeling results of capsid proteins showing that protein delta has a high degree of structural similarity with the rate-limiting enzyme (TDO-2) of the kynurenine pathway. Because TDO-2 controls serotonin production and promotes brain excitability, we can hypothesize that protein δ mimics and/or interferes with host TDO-2 activity. Since hyperactivity has been reported in other virus-human systems, it could be that this behavioral response is evolutionary conserved – a possibility that require further exploration.


Author(s)
Alba Timón-Gómez and Antoni Barrientos

Institute
University of Miami Miller School of Medicine
Address
Departmentof Neurology and Department of Biochemistry and Molecular Biology, University of Miami Miller School ofMedicine, Miami, FL 33136
Abstract:

Mitochondria are the major consumer of oxygen in eukaryotic cells, owing to the requirement of oxygen to generate ATP through the mitochondrial respiratory chain (MRC) and the oxidative phosphorylation system (OXPHOS). This aerobic energy transduction is more efficient than anaerobic processes such as glycolysis. Hypoxia, a condition in which environmental or intracellular oxygen levels are below the standard range, triggers an adaptive signaling pathway within the cell. When oxygen concentrations are low, hypoxia-inducible factors (HIFs) become stabilized and activated to mount a transcriptional response that triggers modulation of cellular metabolism to adjust to hypoxic conditions. Mitochondrial aerobic metabolism is one of the main targets of the hypoxic response to regulate its functioning and efficiency in the presence of decreased oxygen levels. During evolution, ....


Author(s)
Min Qiu and Chao Deng

Institute
Tufts University, USA, Soochow University, China
Address
Tufts University, 4 Colby Street, Medford, MA 02155, USA.
Soochow University, Suzhou, 215123, China.
Abstract:

Biopharmaceutics, such as proteins, nucleic acids, antibodies, have emerged as promising candidates for the treatment of a variety of diseases due to their high specificity and greater bioactivity. However, the intrinsic low biological stability and poor cell membrane penetration ability of biopharmaceutics has largely hindered their utility. Developing efficient cytosolic delivery platforms is, therefore of vital importance to overcome these hurdles and to advance the clinical translation of biopharmaceutic-based therapy. Polymersomes have emerged as superb nanovesicles for sophisticated biophamraceutic delivery, owing to their hydrophobic membranes to protect proteins from enzymatic degradation and vast watery cores for protein loading. This perspective summarizes the current design and applications of polymersomes for the intracellular delivery of therapeutic biopharmaceutics.


Author(s)
Kathrin Bohn-Wippert and Roy D. Dar

Institute
University of Illinois at Urbana-Champaign
Address

1406 West GreenStreet, Urbana, IL 61801, USA, 1206W Gregory Drive,Urbana, Illinois 61801, USA.

Abstract:

Human immunodeficiency virus (HIV) preferentially infects T-lymphocytes by integrating into host DNA and forming a latent transcriptionally silent provirus.  As previously shown, HIV-1 alters migration modes of T-lymphocytes by co-regulating viral gene expression with human C-X-C chemokine receptor-4 (CXCR4). Here, we show that motility of infected T-lymphocytes is cell size dependent. In cell migration assays, migrating cells are consistently larger than non-migrating cells. This effect is drug-treatment independent. The cell size dependent motility observed in a previously generated Jurkat latency model correlates with the motility of primary human CD4+ T-cells containing a modified HIV-1 full-length construct JLatd2GFP. In addition, large migrating T-cells, latently infected with HIV, show a slightly decreased rate of reactivation from latency. these results demonstrate that HIV reactivation is cell migration-dependent, where host cell size acts as a catalyst for altered migration velocity. We believe that host cell size controlled migration uncovers an additional mechanism of cellular controlled viral fate determination important for virus dissemination and reactivation from latency. This observation may provide more insights into viral-host interactions regulating cell migration and reactivation from latency and helps in the design and implementation of novel therapeutic strategies.


Author(s)
Ying Yang

Institute
University of California, Irvine
Address
Department of Molecular Biology and Biochemistry; School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA
Abstract:

Obesity has become a serious health concern worldwide because it is associated with a higher risk of heart diseases, diabetes, and even certain types of cancers. Since diet and lifestyle adjustments could be very challenging, there has been growing interest in dietary supplements to promote bodyweight loss and decrease the relapse rate. Therefore, many different kinds of food supplementations are now popular in the United States; however, the effects and mechanisms of most supplementations are still understudied. It has been established that obesity is characterized by chronic inflammation in white adipose tissue. Interestingly, glutamine, which is normally used to boost the immune system has shown the function of decreasing body weight and composition of fat tissues in humans and animals by reducing obesity-related inflammation. However, the underlying mechanism of dietary glutamine’s effect on obesity is still far from clear. Here, in this review, we will discuss the current understanding of the use of glutamine supplementation as a treatment for obesity. The elucidation of the current dietary strategies using glutamine may highlight new approaches for obesity and diabetes treatment.

 
 
     
 
 
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