scholarly journals Resolving the hypotheticome: annotating M. tuberculosis gene function through bibliomic reconciliation andstructural modeling

2018 ◽  
Author(s):  
Samuel J. Modlin ◽  
Deepika Gunasekaran ◽  
Alyssa M. Zlotnicki ◽  
Afif Elghraoui ◽  
Norman Kuo ◽  
...  

AbstractEach decade, billions are invested in Tuberculosis (TB) research to further characterize M. tuberculosis pathogenesis. Despite this investment, nearly half of the 4,031 M. tuberculosis protein-coding genes lack descriptive annotation in community databases, due largely to incomplete reconciliation with the literature and a lack of structure-based methods for functional inference. We coin the term “hypotheticome” as the set of genes in an organism without known function. For M. tuberculosis’ hypotheticome, we compiled the set of genes lacking functional assignment in the most frequently used Mycobacteria annotation database through systematic, exhaustive manual literature curation and 3D-protein structure-based inference, and reconciled these annotations with frequented functional databases, creating a comprehensive M. tuberculosis functional knowledge-base. In doing so, we also introduce standard usage of qualifying adjectives based on quantitative measures of certainty with the hope that this approach is adopted in choosing qualifiers for future functional assignments.Through these methods we functionally annotated 41.3% of the M. tuberculosis hypotheticome, and provide insight into its pathogenesis, antibiotic-resistance, and virulence. Processes implicated in the unique lifestyle of M. tuberculosis of long-term persistence and obligate pathogenesis in genotoxic host microenvironments – lipid metabolism, polyketide biosynthesis, and membrane transport and efflux – were overrepresented in our annotation. Our structural similarity approach unturned proteins that appear critical in host-interaction through apparent host mimicry, particularly involving the phagosome and vesicle-mediated transport, as well as putative structural analogs for highly mutable protein classes, including dozens of PE/PPE family proteins which are major players at the host-pathogen interface, and sixteen potential efflux pumps which are integral to M. tuberculosis drug tolerance. Hypotheses drawn from these proteins’ function may help characterize the onset of latency and identify therapeutic targets. A unified annotation is essential for clear communication about M. tuberculosis. These improvements provide the most comprehensive M. tuberculosis genome annotation to date, and the approach presented can be applied to systematically annotate the genome of other organisms. We provide our novel annotations in General Feature Format with Enzyme Commission and Gene Ontology terms for integration into existing annotation frameworks.

2019 ◽  
Vol 14 (2) ◽  
pp. 506-518 ◽  
Author(s):  
Mie N. Honjo ◽  
Naoko Emura ◽  
Tetsuhiro Kawagoe ◽  
Jiro Sugisaka ◽  
Mari Kamitani ◽  
...  

Abstract Persistent infection, wherein a pathogen is continually present in a host individual, is widespread in virus–host systems. However, little is known regarding how seasonal environments alter virus–host interaction during such metastability. We observed a lineage-to-lineage infection of the host plant Arabidopsis halleri with Turnip mosaic virus for 3 years without severe damage. Virus dynamics and virus–host interactions within hosts were highly season dependent. Virus accumulation in the newly formed leaves was temperature dependent and was suppressed during winter. Transcriptome analyses suggested that distinct defence mechanisms, i.e. salicylic acid (SA)-dependent resistance and RNA silencing, were predominant during spring and autumn, respectively. Transcriptomic difference between infected and uninfected plants other than defence genes appeared transiently only during autumn in upper leaves. However, the virus preserved in the lower leaves is transferred to the clonal offspring of the host plants during spring. In the linage-to-linage infection of the A. halleri–TuMV system, both host clonal reproduction and virus transmission into new clonal rosettes are secured during the winter–spring transition. How virus and host overwinter turned out to be critical for understanding a long-term virus–host interaction within hosts under temperate climates, and more generally, understanding seasonality provides new insight into ecology of plant viruses.


2015 ◽  
Vol 12 (1) ◽  
pp. 1-12
Author(s):  
Sarah Hackett

Drawing upon a collection of oral history interviews, this paper offers an insight into entrepreneurial and residential patterns and behaviour amongst Turkish Muslims in the German city of Bremen. The academic literature has traditionally argued that Turkish migrants in Germany have been pushed into self-employment, low-quality housing and segregated neighbourhoods as a result of discrimination, and poor employment and housing opportunities. Yet the interviews reveal the extent to which Bremen’s Turkish Muslims’ performances and experiences have overwhelmingly been the consequences of personal choices and ambitions. For many of the city’s Turkish Muslim entrepreneurs, self-employment had been a long-term objective, and they have succeeded in establishing and running their businesses in the manner they choose with regards to location and clientele, for example. Similarly, interviewees stressed the way in which they were able to shape their housing experiences by opting which districts of the city to live in and by purchasing property. On the whole, they perceive their entrepreneurial and residential practices as both consequences and mediums of success, integration and a loyalty to the city of Bremen. The findings are contextualised within the wider debate regarding the long-term legacy of Germany’s post-war guest-worker system and its position as a “country of immigration”.


Author(s):  
Sally Treloyn ◽  
Matthew Dembal Martin ◽  
Rona Goonginda Charles

Repatriation has become almost ubiquitous in ethnomusicological research on Australian Indigenous song. This article provides insights into processes of a repatriation-centered song revitalization project in the Kimberley, northwest Australia. Authored by an ethnomusicologist and two members of the Ngarinyin cultural heritage community, the article provides firsthand accounts of the early phases of a long-term repatriation-centered project referred to locally as the Junba Project. The authors provide a sample of narratives and dialogues that deliver insight into experiences of the work of identifying recordings “in the archive” and cultural negotiation and use of recordings “on Country.” The entanglement of local epistemological frameworks with past and present collection, archival research, repatriation, and dissemination for intergenerational knowledge transmission between spirits, Country, and the living, is explored, showing how recordings move song knowledge from community to archive to community and from generation to generation, and move people in present-day communities. The chapter considers how these “moving songs” allow an interrogation of the fraught endeavor of intercultural collaboration in the pursuit of revitalizing Indigenous song traditions. It positions repatriation as a method that can support intergenerational knowledge transmission and as a method to consider past and present intercultural relationships within research projects and between cultural heritage communities and collecting institutions.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ye Qian ◽  
Yan Zhang ◽  
Haoming Ji ◽  
Yucheng Shen ◽  
Liangfeng Zheng ◽  
...  

Abstract Background Lung adenocarcinoma (LUAD) is one of the most common cancers with high morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) serve as tumor promoters or suppressors in the development of various human malignancies, including LUAD. Although long intergenic non-protein coding RNA 1089 (LINC01089) suppresses the progression of breast cancer, its mechanism in LUAD requires further exploration. Thus, we aimed to investigate the underlying function and mechanism of LINC01089 in LUAD. Methods The expression of LINC01089 in LUAD and normal cell lines was detected. Functional assays were applied to measure cell proliferation, apoptosis and migration. Besides, mechanism experiments were employed for assessing the interplay among LINC01089, miR-301b-3p and StAR related lipid transfer domain containing 13 (STARD13). Data achieved in this study was statistically analyzed with Student’s t test or one-way analysis of variance. Results LINC01089 expression was significantly down-regulated in LUAD tissues and cells and its overexpression could reduce cell proliferation and migration. Moreover, LINC01089 could regulate STARD13 expression through competitively binding to miR-301b-3p in LUAD. Additionally, rescue assays uncovered that STARD13 depletion or miR-301b-3p overexpression could countervail the restraining effect of LINC01089 knockdown on the phenotypes of LUAD cells. Conclusion LINC01089 served as a tumor-inhibitor in LUAD by targeting miR-301b-3p/STARD13 axis, providing an innovative insight into LUAD therapies. Trial registration Not applicable.


2020 ◽  
Vol 48 (7) ◽  
pp. 030006052094211
Author(s):  
Wei Zhang ◽  
Feng Xue ◽  
Quandong Bu ◽  
Xuemei Liu

Hypocalcemia is a rare, but reversible, cause of dilated cardiomyopathy. Although cardiomyopathy may cause severe heart failure, calcium supplementation can reverse heart failure. We report here a patient with uremia and secondary hyperparathyroidism, who was complicated by persistent hypocalcemia and refractory heart failure. The cardiac failure was refractory to treatment with digitalis and diuretics, but dramatically responded to calcium therapy and restoration of normocalcemia. As a result, the patient was eventually diagnosed with hypocalcemic cardiomyopathy. To the best of our knowledge, this is the first case of this disease to be reported in a patient with uremia. Findings from our case may help clinicians to better understand hypocalcemic cardiomyopathy. Our case might also provide new insight into long-term cardiac complications and prognoses of patients undergoing parathyroidectomy due to secondary hyperparathyroidism.


1998 ◽  
Vol 11 (1) ◽  
pp. 379-379
Author(s):  
P.L. Cottrell ◽  
L. Skuljan ◽  
P.M. Kilmartin ◽  
C. Gilmore ◽  
W.A. Lawson

For more than a decade we have been able to acquire and analyse a significant amount of photometric data of the highly variable R Coronae Borealis (RCB) stars. This has made been possible by a photometric service observing programme instigated at the Observatory. These photometric data have been combined with less extensive spectroscopic coverage, particularly of the decline phase of these stars. These have been supplemented by observations obtained at Mount Stromlo and Siding Spring Observatories for a radial velocity study. Significantly more spectroscopic observations are now being acquired with the development of a new medium resolution spectrograph at Mount John University Observatory. In this poster we will present recent photometric and spectroscopic results for a number of the RCB stars in our sample. This observational and analysis work can be used to provide further insight into the nature of these stars, their likely progeny and progenitors and the processes that are involved in the formation and evolution of the obscuring dust clouds which cause the decline phase.


2020 ◽  
Vol 55 (3) ◽  
pp. 151-162
Author(s):  
Danuta Urban ◽  
Joanna Sender ◽  
Ewelina Tokarz ◽  
Andrzej Różycki

AbstractIn view of the sensitivity of Liparis loeselii to changes in habitat conditions, we carried out a study with the aim to monitor population numbers, identify the individual features of the Liparis loeselii population, analyse habitat conditions, identify threats and propose conservation measures to preserve the species. The investigations were conducted in seven unmanaged objects located in three Natura 2000 areas in eastern Poland. The results of this study provide a new insight into Liparis loeselii ecology. The analysed populations inhabited some habitat types: extremely poor fen, transitional mire, rich fen, calcareous fen, spring-fed fen. The content of nutrients was similar in all the habitats. A CCA analysis revealed that the total carbon content, pH, and redox potential of the substrate determine differences between the habitats analysed. Juvenile individuals represented a maximum of 12% of the analysed populations and were the least abundant group of these plants. The flowering was primarily influenced by hydrological conditions. Based on the long-term observations reported in this article, it can be assumed that the species stands a chance of surviving at the localities analysed, provided that the habitat conditions do not change dramatically.


2019 ◽  
Vol 223 (2) ◽  
pp. 675-691 ◽  
Author(s):  
Fraser Kennedy ◽  
Andrew Martin ◽  
John P. Bowman ◽  
Richard Wilson ◽  
Andrew McMinn

2021 ◽  
pp. 146144482199671
Author(s):  
Jeanna Sybert

On December 3, 2018, Tumblr announced that it would ban sexually explicit content from the platform, drawing immediate backlash from users. The ensuing discord on the site is conceptualized here as contested platform governance, or a conflict between users and ownership, in which not only are a platform’s policies and features challenged, but also its core values, identity, and/or purposes are put into question. By examining 238 Tumblr posts, this analysis identifies the unique ways users combatted the ban and (re)inscribed community values, while also contesting the owners’ legitimacy to govern the platform. Holding implications for the site’s long-term survival, such conflicts capture a critical moment in which the boundaries of power between users and ownership are challenged and, possibly, transformed. By examining Tumblr’s Not Safe For Work (NSFW) ban through the lens of platform governance, this study offers insight into how power and its limits are negotiated online.


Author(s):  
Parisa Dehghani ◽  
Monireh Esameili Rad ◽  
Atefeh Zarepour ◽  
Ponnurengam Malliappan Sivakumar ◽  
Ali Zarrabi

: Diabetes mellitus (DM) is a type of chronic metabolic disease that has affected millions of people worldwide and is known with a defect in the amount of insulin secretion, insulin functions, or both. This deficiency leads to an increase in the amounts of glucose, which could be accompanied by long-term damages to other organs such as eyes, kidneys, heart, and nervous system. Thus, introducing an appropriate approach for diagnosis and treatment of different types of DM is the aim of several researches. By the emergence of nanotechnology and its application in medicine, new approaches were presented for these purposes. The object of this review article is to introduce different types of polymeric nanoparticles (PNPs), as one of the most important classes of nanoparticles, for diabetic management. To achieve this goal, at first, some of the conventional therapeutic and diagnostic methods of DM will be reviewed. Then, different types of PNPs, in two forms of natural and synthetic polymers with different properties, as a new method for DM treatment and diagnosis will be introduced. In the next section, the transport mechanisms of these types of nano-carriers across the epithelium, via paracellular and transcellular pathways will be explained. Finally, the clinical use of PNPs in the treatment and diagnosis of DM will be summarized. Based on the results of this literature review, PNPs could be considered one of the most promising methods for DM management.


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