ResearchPad - Multidisciplinary https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Applying high-performance computing in drug discovery and molecular simulation]]> https://www.researchpad.co/product?articleinfo=N572d7b38-36c7-4be4-9699-cb9b27c22055

Abstract

In recent decades, high-performance computing (HPC) technologies and supercomputers in China have significantly advanced, resulting in remarkable achievements. Computational drug discovery and design, which is based on HPC and combines pharmaceutical chemistry and computational biology, has become a critical approach in drug research and development and is financially supported by the Chinese government. This approach has yielded a series of new algorithms in drug design, as well as new software and databases. This review mainly focuses on the application of HPC to the fields of drug discovery and molecular simulation at the Chinese Academy of Sciences, including virtual drug screening, molecular dynamics simulation, and protein folding. In addition, the potential future application of HPC in precision medicine is briefly discussed.

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<![CDATA[Habitat degradation negatively affects auditory settlement behavior of coral reef fishes]]> https://www.researchpad.co/product?articleinfo=5b59c8b8463d7e7b3acb09bc

Significance

Climate change is causing widespread damage to the world’s tropical coral reefs, via increases in cyclones and mass bleaching. Healthy populations of reef fishes facilitate recovery from such events, and recruitment of juvenile fish is influenced by acoustic cues that guide larval orientation, habitat selection, and settlement to reefs. Our matched recordings of Australia’s Great Barrier Reef before and after recent severe degradation demonstrate major changes to natural reef sound. In field experiments using these recordings, we show the potential impact of such acoustic changes. Postdegradation reef sounds were less attractive to young fishes than their predegradation equivalents. Reductions in fish settlement, caused by acoustic changes, may threaten the recovery potential of degraded coral reefs.

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<![CDATA[Retraction: Murine hypothalamic destruction with vascular cell apoptosis subsequent to combined administration of human papilloma virus vaccine and pertussis toxin]]> https://www.researchpad.co/product?articleinfo=5b59ab78463d7e792f619090 ]]> <![CDATA[Social contagion of ethnic hostility]]> https://www.researchpad.co/product?articleinfo=5b598f47463d7e76cf8ed8ce

Significance

We provide experimental evidence on peer effects and show that behavior that harms members of a different ethnic group is twice as contagious as behavior that harms coethnics. The findings may help to explain why ethnic hostilities can spread quickly (even in societies with few visible signs of interethnic hatred) and why many countries have adopted hate crime laws, and illustrate the need to study not only the existence of discrimination, but also the stability of attitudes and behaviors toward outgroup members.

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<![CDATA[Early events during human coronavirus OC43 entry to the cell]]> https://www.researchpad.co/product?articleinfo=5bffc501d5eed0c484baca8e

The Coronaviridae family clusters a number of large RNA viruses, which share several structural and functional features. However, members of this family recognize different cellular receptors and exploit different entry routes, what affects their species specificity and virulence. The aim of this study was to determine how human coronavirus OC43 enters the susceptible cell. Using confocal microscopy and molecular biology tools we visualized early events during infection. We found that the virus employs caveolin-1 dependent endocytosis for the entry and the scission of virus-containing vesicles from the cell surface is dynamin-dependent. Furthermore, the vesicle internalization process requires actin cytoskeleton rearrangements. With our research we strove to broaden the understanding of the infection process, which in future may be beneficial for the development of a potential therapeutics.

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<![CDATA[The computational form of craving is a selective multiplication of economic value]]> https://www.researchpad.co/product?articleinfo=5b58d4eb463d7e51d5394785

Significance

Craving is a specific desire state that biases choice toward the desired object. Although extremely common, and in its pathological form a major contributor to negative health outcomes as in addiction and obesity, craving is not well understood. In a laboratory model of craving, we find “craving” is reflected in people’s momentary willingness to pay for the things they desire, and for subjectively similar things, consistent with a transient, good-selective change in subjective valuation. We further find the value of the desired goods increases multiplicatively, which might explain several escalation behaviors associated with craving in real-world environments. This opens more lines of research regarding the computational form of craving in health and disease, with implications for marketing actions and consumer choice.

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<![CDATA[Land use strategies to mitigate climate change in carbon dense temperate forests]]> https://www.researchpad.co/product?articleinfo=5b4d0d3b463d7e142d5b64ea

Significance

Regional quantification of feasibility and effectiveness of forest strategies to mitigate climate change should integrate observations and mechanistic ecosystem process models with future climate, CO2, disturbances from fire, and management. Here, we demonstrate this approach in a high biomass region, and found that reforestation, afforestation, lengthened harvest cycles on private lands, and restricting harvest on public lands increased net ecosystem carbon balance by 56% by 2100, with the latter two actions contributing the most. Forest sector emissions tracked with our life cycle assessment model decreased by 17%, partially meeting emissions reduction goals. Harvest residue bioenergy use did not reduce short-term emissions. Cobenefits include increased water availability and biodiversity of forest species. Our improved analysis framework can be used in other temperate regions.

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<![CDATA[Direct observation of ultrafast large-scale dynamics of an enzyme under turnover conditions]]> https://www.researchpad.co/product?articleinfo=5b4ce39d463d7e10fe544866

Significance

The potential effect of conformational dynamics of enzymes on their chemical steps has been intensely debated recently. We use single-molecule FRET experiments on adenylate kinase (AK) to shed new light on this question. AK closes its domains to bring its two substrate close together for reaction. We show that domain closure takes only microseconds to complete, which is two orders of magnitude faster than the chemical reaction. Nevertheless, active-site mutants that reduce the rate of domain closure also reduce the reaction rate, suggesting a connection between the two phenomena. We propose that ultrafast domain closure is used by enzymes as a mechanism to optimize mutual orientation of substrates, a novel mode of coupling between conformational dynamics and catalysis.

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<![CDATA[Origins and genetic legacies of the Caribbean Taino]]> https://www.researchpad.co/product?articleinfo=5b4cd8bc463d7e0fba429e04

Significance

Ancient DNA has revolutionized the field of archaeology, but in the Caribbean and other tropical regions of the world, the work has been hampered by poor DNA preservation. We present an ancient human genome from the Caribbean and use it to shed light on the early peopling of the islands. We demonstrate that the ancestors of the so-called “Taino” who inhabited large parts of the Caribbean in pre-Columbian times originated in northern South America, and we find evidence that they had a comparatively large effective population size. We also show that the native components in some modern Caribbean genomes are closely related to the ancient Taino, suggesting that indigenous ancestry in the region has survived through the present day.

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<![CDATA[Structural basis for the role of serine-rich repeat proteins from Lactobacillus reuteri in gut microbe–host interactions]]> https://www.researchpad.co/product?articleinfo=5b4c79ea463d7e0c20d25f19

Significance

Gut bacteria play a key role in health and disease, but the molecular mechanisms underpinning their interaction with the host remain elusive. The serine-rich repeat proteins (SRRPs) are a family of adhesins identified in many Gram-positive pathogenic bacteria. We previously showed that beneficial bacterial species found in the gut also express SRRPs and that SRRP was required for the ability of Lactobacillus reuteri strain to colonize mice. Here, our structural and biochemical data reveal that L. reuteri SRRP adopts a β-solenoid fold not observed in other structurally characterized SRRPs and functions as an adhesin via a pH-dependent mechanism, providing structural insights into the role of these adhesins in biofilm formation of gut symbionts.

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<![CDATA[MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity]]> https://www.researchpad.co/product?articleinfo=5bfb7cc7d5eed0c484a9dbdf

Significance

Middle East respiratory syndrome (MERS) is a zoonotic disease of global health concern, and dromedary camels are the source of human infection. Although Africa has the largest number of dromedary camels, and MERS-coronavirus (MERS-CoV) is endemic in these camels, locally acquired zoonotic MERS is not reported from Africa. However, little is known of the genetic or phenotypic characterization of MERS-CoV from Africa. In this study we characterize MERS-CoV from Burkina Faso, Nigeria, Morocco, and Ethiopia. We demonstrate viral genetic and phenotypic differences in viruses from West Africa, which may be relevant to differences in zoonotic potential, highlighting the need for studies of MERS-CoV at the animal–human interface.

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<![CDATA[Erratum: Reducing Cascading Failure Risk by Increasing Infrastructure Network Interdependence]]> https://www.researchpad.co/product?articleinfo=5b4c15c7463d7e0329bcc43d ]]> <![CDATA[The ‘Plantain-Optim’ dataset: Agronomic traits of 405 plantains every 15 days from planting to harvest]]> https://www.researchpad.co/product?articleinfo=5b4bf0c7463d7e7f7e212c4f

The ‘Plantain-Optim’ dataset (came from the ‘Plantain-Optim’ experiment conducted from 2009 to 2011 at CARBAP experimental station in Cameroon. The main objective was to describe agronomic potential of nine plantain varieties, including five natural plantains commonly cropped in Cameroon, and four plantain-like hybrids. A completely randomized bloc permitted to compare growth, development and yield of 45 plants per variety split between five replicates. Cropping practices guarantied non-limiting and homogenous conditions. Each plant was measured every 15 days. Data described aerial organ sizes, foliar structure and bunch characteristics of the mother plant. The ‘Plantain-Optim’ dataset includes the complete individual growth of each studied plantain of the ‘Plantain-Optim’ experiment with a 15-day accuracy. It is a useful standard of plantain varietal diversity for comparison with others datasets. Varietal growth and development homogeneity, biomass production or foliar and bunch structures could be further investigated. Moreover, these accurate data on plantain growth could be valuable for plantain 3D modelling.

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<![CDATA[Data on genetic associations of carotid atherosclerosis markers in Mexican American and European American rheumatoid arthritis subjects]]> https://www.researchpad.co/product?articleinfo=5b4bb850463d7e7b755cb5b5

Carotid Intima-media thickness (CIMT) and plaque are well established markers of subclinical atherosclerosis and are widely used for identifying subclinical atherosclerotic disease. We performed association analyses using Metabochip array to identify genetic variants that influence variation in CIMT and plaque, measured using B-mode ultrasonography, in rheumatoid arthritis (RA) patients. Data on genetic associations of common variants associated with both CIMT and plaque in RA subjects involving Mexican Americans (MA) and European Americans (EA) populations are presented in this article. Strong associations were observed after adjusting for covariate effects including baseline clinical characteristics and statin use. Susceptibility loci and genes and/or nearest genes associated with CIMT in MAs and EAs with RA are presented. In addition, common susceptibility loci influencing CIMT and plaque in both MAs and EAs have been presented. Polygenic Risk Score (PRS) plots showing complementary evidence for the observed CIMT and plaque association signals are also shown in this article. For further interpretation and details, please see the research article titled “A Genetic Association Study of Carotid Intima-Media Thickness (CIMT) and Plaque in Mexican Americans and European Americans with Rheumatoid Arthritis” which is being published in Atherosclerosis (Arya et al., 2018) [1].(Arya et al., in press) Thus, common variants in several genes exhibited significant associations with CIMT and plaque in both MAs and EAs as presented in this article. These findings may help understand the genetic architecture of subclinical atherosclerosis in RA populations.

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<![CDATA[Survey datasets on women participation in green jobs in the construction industry]]> https://www.researchpad.co/product?articleinfo=5b4ba611463d7e7a50b84a53

The unique qualities of women can make them bearers of solutions towards achieving sustainability and dealing with the dangers attributed to climate change. The attitudinal study utilized a questionnaire instrument to obtain perception of female construction professionals. By using a well-structured questionnaire, data was obtained on women participating in green jobs in the construction Industry. Descriptive statistics is performed on the collected data and presented in tables and mean scores (MS). In addition, inferential statistics of categorical regression was performed on the data to determine the level of influence (beta factor) the identified barriers had on the level of participation in green jobs. Barriers and the socio-economic benefits which can guide policies and actions on attracting, retaining and exploring the capabilities of women in green jobs can be obtained from the survey data when analyzed.

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<![CDATA[Phylogenetic classification of the world’s tropical forests]]> https://www.researchpad.co/product?articleinfo=5b4b41c7463d7e74e8896821

Significance

Identifying and explaining regional differences in tropical forest dynamics, structure, diversity, and composition are critical for anticipating region-specific responses to global environmental change. Floristic classifications are of fundamental importance for these efforts. Here we provide a global tropical forest classification that is explicitly based on community evolutionary similarity, resulting in identification of five major tropical forest regions and their relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. African and American forests are grouped, reflecting their former western Gondwanan connection, while Indo-Pacific forests range from eastern Africa and Madagascar to Australia and the Pacific. The connection between northern-hemisphere Asian and American forests is confirmed, while Dry forests are identified as a single tropical biome.

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<![CDATA[Field migration rates of tidal meanders recapitulate fluvial morphodynamics]]> https://www.researchpad.co/product?articleinfo=5b4b0354463d7e70c3bdeaf8

Significance

Meandering tidal channel networks play a central role in the ecomorphodynamic evolution of the landscapes they cut through. Despite their ubiquitous presence and relevance to sedimentary and landscape features, few observations of tidal-meander evolution exist, and we lack a full understanding of the governing processes. Field analyses show that tidal meanders, traditionally viewed as stable landscape features, display modes of migration and migration rates per unit width quite similar to those characterizing their fluvial counterparts, with important implications for the characterization of the related sedimentary products. The results presented here contribute to our understanding of the morphological evolution of tidal landscapes.

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<![CDATA[Methyltransferases of gentamicin biosynthesis]]> https://www.researchpad.co/product?articleinfo=5b4b060d463d7e70c3bdeb02

Significance

Aminoglycosides remain a vital clinical asset. Gentamicin C complex in particular is remarkably potent in treating systemic Gram-negative infections, and semisynthetic gentamicins that combat pathogen resistance or show reduced toxicity remain attractive goals. We report here the roles of clustered genes and enzymes that define a methylation network in gentamicin biosynthesis and also identify a remote gene on the chromosome encoding the essential methyltransferase GenL, which is decisive for the proportions of the five major components present in the gentamicin C complex. This is an important step toward engineered fermentation to produce single components as valuable starting materials for semisynthesis of next-generation aminoglycoside antibiotics.

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<![CDATA[MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape]]> https://www.researchpad.co/product?articleinfo=5bf5834cd5eed0c4849a0521

Significance

Both highly pathogenic avian influenza virus and Middle East respiratory syndrome coronavirus (MERS-CoV) infections are characterized by severe disease and high mortality. The continued threat of their emergence from zoonotic populations underscores an important need to understand the dynamics of their infection. By comparing the host responses across other related respiratory virus infections, these studies have identified a common avenue used by MERS-CoV and A/influenza/Vietnam/1203/2004 (H5N1-VN1203) influenza to antagonize antigen presentation through epigenetic modulation. Overall, the use of cross-comparisons provides an additional approach to leverage systems biology data to identify key pathways and strategies used by viruses to subvert host immune responses and may be critical in developing both vaccines and therapeutic treatment.

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<![CDATA[Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function]]> https://www.researchpad.co/product?articleinfo=5bf5153bd5eed0c4848721b2

Significance

Cytokines interact with their receptors and activate JAK–STAT signaling pathways that lead to changes in gene expression. In mammals, there are seven STATs that have arisen due to gene duplication and genetic drift. STATs have similar DNA binding specificity, and how individual STATs have subfunctionalized to regulate very specific cytokine responses in cells is poorly understood. Here we describe X-ray structures that show how one STAT family member, STAT2, specifically pairs with a member of the IRF family of transcription factors, IRF9. Despite overall structural similarity among STAT and IRF family members, surface features in the interacting domains of IRF9 and STAT2 have diverged to enable specific interaction between these family members and to enable the antiviral response.

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