Biology subjects

Dong, T.

Publications and source records attributed to Dong, T..

4 recordsLinked to original sources

bioRxiv2018

Nemo-like kinase regulates Progranulin levels in the brain through the microglial endocytosis-lysosomal pathway

Genetic variants in Granulin (GRN), which encodes the secreted glycoprotein Progranulin (PGRN), are associated with several neurodegenerative diseases including frontotemporal lobar degeneration, neuronal ceroid lipofuscinosis, and Alzheimers disease. These genetic alterations manifest in pathological changes due to a reduction of PGRN expression; therefore, identifying a factor that can modulate PGRN levels in vivo would enhance our understanding of PGRN in neurodegeneration, and could reveal novel potential therapeutic targets. Here, we report that Nemo-like kinase (Nlk) regulates Pgrn levels and its associated neuropathophysiology. Genetic interaction studies in mice show that Grn heterozygote mice on an Nlk heterozygote background display pathological and behavioral phenotypes which mimic Grn knockout mice. Furthermore, biochemical and cell biological studies suggest that Nlk reduction promotes Pgrn degradation via the endocytosis-lysosomal pathway, specifically in microglia. Our results reveal a new mechanism for the regulation of Pgrn in the brain and provide insight into the pathophysiology of PGRN-associated diseases.

neuroscience↗

bioRxiv2018

Factors Associated with Scientific Misconduct and Questionable Research Practices in Health Professions Education

IntroductionEngaging in scientific misconduct and questionable research practices (QRPs) is a noted problem across fields, including health professions education (HPE). To mitigate these practices, other disciplines have enacted strategies based on researcher characteristics and practice factors. Thus, to inform HPE, this article seeks to determine which researcher characteristics and practice factors, if any, might explain the frequency of irresponsible research practices.\n\nMethodIn 2017, a cross-sectional survey of HPE researchers was conducted. The survey included 66 items derived from two published QRP surveys and a publication pressure scale adapted from the literature. The study outcome was the self-reported misconduct frequency score, which is a weighted mean score for each respondent on all misconduct and QRP items. Statistical analysis included descriptive statistics, correlation analysis, and multiple linear regression analysis.\n\nResults and DiscussionIn total, 590 researchers took the survey. Results from the regression analysis indicated that researcher age had a negative association with the misconduct frequency score (b = -.01, t = -2.91, p<.05) suggesting that older researchers tended to have lower misconduct frequency scores. Publication pressure (b = .20, t = 7.82, p<.001) and number of publications (b = .001, t = 3.27, p<.01) had positive associations with the misconduct frequency score. The greater the publication pressure or the more publications a researcher reported, the higher the misconduct frequency score. Overall, the explanatory variables accounted for 21% of the variance in the misconduct frequency score, and publication pressure was the strongest predictor. These findings provide an evidence base from which HPE might tailor strategies to address scientific misconduct and QRPs.

scientific communication and education↗

bioRxiv2017

Distinct antibody-mediated selection in a narrow-source HIV-1 outbreak among Chinese former plasma donors

The HIV-1 envelope protein mutates rapidly to evade recognition and killing, and is a major target of the humoral immune response and in vaccine development. Identification of common antibody epitopes for vaccine development have been complicated by large variations on both virus (different infecting founder strains) and host genetic levels. We studied HIV-1 envelope gp120 evolution in 12 Chinese former plasma donors infected with a purportedly single founder virus, with the aim of identifying common antibody epitopes under immune selection. We found five amino acid sites to be under significant positive selection in [≥]50% of the patients, and 22 sites housing mutations consistent with antibody-mediated selection. Despite strong selection pressure, some sites housed a limited repertoire of amino acids. Structural modelling revealed that most sites were located on the exposed distal edge of the Gp120 trimer, whilst wholly invariant sites clustered within the centre of the protein complex. Four sites, flanking the V3 hypervariable loop of the Gp120, represent novel antibody epitopes that may be suitable as vaccine candidates.

immunology↗

bioRxiv2017

Wikipedia as a gateway to biomedical research: The relative distribution and use of citations in the English Wikipedia

Wikipedia is a gateway to knowledge. However, the extent to which this gateway ends at Wikipedia or continues via supporting citations is unknown. Wikipedias gateway functionality has implications for information design and education, notably in medicine. This study aims to establish benchmarks for the relative distribution and referral (click) rate of citations--as indicated by presence of a Digital Object Identifier (DOI)--from Wikipedia, with a focus on medical citations.\n\nDOIs referred from the English Wikipedia in August 2016 were obtained from Crossref.org. Next, based on a DOIs presence on a WikiProject Medicine page, all DOIs in Wikipedia were categorized as medical (WP:MED) or non-medical (non-WP:MED). Using this categorization, referred DOIs were classified as WP:MED, non-WP:MED, or BOTH, meaning the DOI may have been referred from either category. Data were analyzed using descriptive and inferential statistics.\n\nOut of 5.2 million Wikipedia pages, 4.42% (n=229,857) included at least one DOI. 68,870 were identified as WP:MED, with 22.14% (n=15,250) featuring one or more DOIs. WP:MED pages featured on average 8.88 DOI citations per page, whereas non-WP:MED pages had on average 4.28 DOI citations. For DOIs only on WP:MED pages, a DOI was referred every 2,283 pageviews and for non-WP-MED pages every 2,467 pageviews. DOIs from BOTH pages accounted for 12% (n=58,475) of referrals, making determining a referral rate for BOTH impossible.\n\nWhile these results cannot provide evidence of greater citation referral from WP:MED than non-WP:MED, they do provide benchmarks to assess strategies for changing referral patterns. These changes might include editors adopting new methods for designing and presenting citations or the introduction of teaching strategies that address the value of consulting citations as a tool for extending learning.

scientific communication and education↗