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A Nuclear Role For Atg8-family Proteins

Autophagy jul20Anne-Claire Jacomin, Stavroula Petridi, Marisa Di Monaco, and Ioannis P. Nezis

Despite the growing evidence that the macroautophagy/autophagy-related protein LC3 is localized in the nucleus, why and how it is targeted to the nucleus are poorly understood. In our recent study, we found that transcription factor seq interacts via its LIR motif with Atg8a to negatively regulate the transcription of autophagy genes. Atg8a was found to also interact with the nuclear acetyltransferase complex subunit and deacetylase. Modulation of the acetylation status of Atg8a affects the interaction between seq and Atg8a, and controls the induction of autophagy. Our work revealed a novel nuclear role for Atg8a, which is linked with the transcriptional regulation of autophagy genes.

Autophagy. July 2020

Mon 10 Aug 2020, 08:55 | Tags: Biomedical Science

Rotavirus group: A genotype circulation patterns across Kenya before and after nationwide vaccine introduction, 2010-2018

BMC Infectious DiseasesMwanga, Mike J., Owor , Betty E., Ochieng , John B., Ngama , Mwanajuma H., Ogwel , Billy , Onyango, Clayton , Juma , Jane , Njeru, Regina, Gicheru, Elijah, Oteno, Grieven P., Khagayi, Sammy, Agoti, Charles N., Bigogo, Godfrey M., Omore, Richard, Addo, Yaw O., Mapaseka, Seheri , Tate, Jacqueline E., Parashar, Umesh D., Hunsperger, Elizabeth , Verani, Jennifer R., Breiman, Robert F. and Nokes, D. James

Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization in 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- and post-RVA vaccine introduction. Stool samples were collected from children aged < 13 years were screened for RVA using enzyme linked immunosorbent assay and VP7 and VP4 genes sequenced to infer genotypes. Genotype prevalence variations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.

BMC Infectious Diseases. July 2020

Wed 05 Aug 2020, 08:46 | Tags: Biomedical Science

Anticipating future learning affects current control decisions: A comparison between passive and active adaptive management in an epidemiological setting

J.Theoretical BiologyBenjamin D Atkins, Chris P Jewell, Michael C Runge, Matthew J Ferrari, Katriona Shea, William JM Probert, Michael J Tildesley

Infectious disease epidemics present a difficult task for policymakers, requiring the implementation of control strategies under significant time constraints and uncertainty. Mathematical models can be used to predict the outcome of control interventions. However, these models suffer in the early stages of an outbreak from a lack of accurate, relevant information regarding the dynamics and spread of the disease and the efficacy of control. As such, recommendations provided by these models are often incorporated in an ad hoc fashion, as and when more reliable information becomes available. In this work, find that the method of incorporating new data can lead to different results that may influence initial policy decisions, with an active AM approach to management providing better information that can lead to more desirable outcomes from an epidemic.

Journal of Theoretical Biology. July 2020

Mon 03 Aug 2020, 09:17 | Tags: Biomedical Science

Moderate changes in CO2 modulate the firing of neurons in the VTA and substantia nigra

iScience jul20Emily Hill, Nicholas Dale, Mark J Wall 

The substantia nigra (SN) and ventral tegmental area (VTA) are vital for the control of movement, goal-directed behaviour and encoding reward. Here we show that the firing of specific neuronal subtypes in these nuclei can be modulated by physiological changes in the partial pressure of carbon dioxide (PCO2). We provide several lines of evidence that this CO2-sensitive conductance results from connexin 26 (Cx26) hemichannel expression. Since the levels of PCO2 in the blood will vary depending on physiological activity and pathology, this suggests that changes in PCO2 could potentially modulate motor activity, reward behaviour and wakefulness.

iScience. July 2020

Fri 31 Jul 2020, 09:21 | Tags: Biomedical Science

Atomistic mechanism of transmembrane helix association

PLoS Computational BiologyJan Domański, Mark S. P. Sansom, Phillip J. Stansfeld, Robert B. Best

Transmembrane helix association is a fundamental step in the folding of helical membrane proteins. The prototypical example of this association is formation of the glycophorin dimer. While its structure and stability have been well-characterized experimentally, the detailed assembly mechanism is harder to obtain. Here, we use all-atom simulations within phospholipid membrane to study glycophorin association. Our results yield an atomistic description of the mechanism for a simple prototype of helical membrane protein folding.

PLoS Computational Biology. June 2020

Wed 29 Jul 2020, 08:44 | Tags: Biomedical Science

The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure

Nature CommunicationsRobert E. Turnbull, Louise Fairall, Almutasem Saleh, Emma Kelsall, Kyle L. Morris, T. J. Ragan, Christos G. Savva, Aditya Chandru, Christopher J. Millard, Olga V. Makarova, Corinne J. Smith, Alan M. Roseman, Andrew M. Fry, Shaun M. Cowley & John W. R. Schwabe

MiDAC is one of seven distinct, large multi-protein complexes that reocruit class I histone deacetylases to the genome to regulate gene expression. Despite implications of involvement in cell cycle regulation and in several cancers, surprisingly little is known about the function or structure of MiDAC. Here we show that MiDAC is important for chromosome alignment during mitosis in cancer cell lines. Our results suggest that MiDAC has an essential and unique function that cannot be compensated by other HDAC complexes, and the complex may target multiple nucleosomes implying a processive deacetylase function.

Nature Communications. June 2020

Wed 22 Jul 2020, 08:42 | Tags: Biomedical Science

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