bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spatial configuration of biotic interactions shapes coexistence-area relationships in an annual plant community
Authors: García-Callejas David , Bartomeus Ignasi , Godoy Oscar 
Published: April 2021

AbstractThe increase of species richness with area is a universal phenomenon on Earth. How-ever, this observation contrasts with our poor understanding of how these species-area relationships (SARs) emerge from the collective effects of area, spatial heterogeneity, and local interactions. By combining a structuralist approach with five years of empirical observations in a highly-diverse Mediterranean grassland, we show that spatial hetero-geneity plays a little role in the accumulation of species richness with area in our system. Instead, as we increase the sampled area more species combinations are realized, and they coexist mainly due to direct pairwise interactions rather than by changes in single-species dominance or by indirect interactions. We also identify a small set of transient species with small population sizes that are consistently found across spatial scales. These findings empirically support the importance of the architecture of species interactions together with stochastic events for driving coexistence- and species-area relationships.
Curvature-driven feedback on aggregation-diffusion of proteins in lipid bilayers
Authors: Mahapatra Arijit , Saintillan David , Rangamani Padmini 
Published: April 2021

AbstractMembrane bending is an extensively studied problem from both modeling and experimental perspectives because of the wide implications of curvature generation in cell biology. Many of the curvature generating aspects in membranes can be attributed to interactions between proteins and membranes. These interactions include protein diffusion and formation of aggregates due to protein-protein interactions in the plane of the membrane. Recently, we developed a model that couples the in-plane flow of lipids and diffusion of proteins with the out-of-plane bending of the membrane. Building on this work, here, we focus on the role of explicit aggregation of proteins on the surface of the membrane in the presence of membrane bending and diffusion. We develop a comprehensive framework that includes lipid flow, membrane bending energy, the entropy of protein distribution, and an explicit aggregation potential and derive the governing equations. We compare this framework to the Cahn-Hillard formalism to predict the regimes in which the proteins form patterns on the membrane. We demonstrate the utility of this model using numerical simulations to predict how aggregation and diffusion, coupled with curvature generation, can alter the landscape of membrane-protein interactions.
Phylomedicine of mutational processes in somatic cancer cell populations
Authors: Miura Sayaka , Vu Tracy , Choi Jiyeong , Kumar Sudhir 
Published: April 2021

ABSTRACTMutational processes in somatic cancer cell populations are constantly changing, leaving their signatures in the accumulated genomic variation in tumors. The inference of mutational signatures from the observed genetic variation enables spatiotemporal tracking of tumor mutational processes that evolve due to cellular environmental changes, mutations, and treatment regimes. Ultimately, mutational patterns illuminate the mechanistic understanding of their evolution in cancer progression. We show that the integration of cancer cell phylogeny with mutational signature deconvolution enables higher-resolution detection of gain and loss of mutational processes within the phylogeny. This approach to analyzing somatic genomic variations in 61 lung cancer patients revealed a high turn-over of mutational processes over time and closely related clonal lineages. Some mutational signatures (e.g., smoking-related) showed a higher propensity to be lost, whereas others (e.g., AID/APOBEC) were gained during lung tumors evolution. These observations shed light on the evolution of mutational processes in somatic cell evolution.
Study of the effectiveness of partial quarantines applied to control the spread of the Covid-19 virus
Authors: León A. 
Published: April 2021

AbstractIn Chile and in many countries of the world, partial quarantines have been used as part of the strategy to contain and control the Covid-19 virus. However, there is no certainty of its effectiveness and efficiency due to the lack of comparison with similar scenarios. In this work, we formulated a theoretical model of individual mobility, which also incorporates the infection dynamics of Covid-19. The model is based on a cellular automaton, which includes individuals moving through the represented spatial region and interacting according to the dynamics of Covid-19. In addition, we include mobile and partial health barriers, and different mobility regimes. Our results show that, partial quarantines would not be effective in general, to reduce the peak of active individuals infected with the virus, except for some proportions of territorial area involved in the division of the global region. Another interesting result of our research is that the passage restrictions in a sanitary barrier would not be relevant to the impact of the pandemic indicators in a sanitary quarantine regime. A possible explanation for the ineffectiveness of partial quarantines lies in the fact that the sanitary barriers are permeable to infected individuals and therefore when one of these individuals passes, an outbreak occurs in the virus-free zone that is independent of the original one.
Dipeptides are minimalistic but sufficient for liquid-liquid phase separation
Authors: Tang Yiming , Bera Santu , Yao Yifei , Zeng Jiyuan , Lao Zenghui , Dong Xuewei , Gazit Ehud , Wei Guanghong 
Published: April 2021

AbstractLiquid-liquid phase separation (LLPS) of proteins mediates the assembly of biomolecular condensates involved in physiological and pathological processes. Identifying the minimalistic building blocks and the sequence determinant of protein phase separation is of urgent importance but remains challenging due to the enormous sequence space and difficulties of existing methodologies in characterizing the phase behavior of ultrashort peptides. Here we demonstrate computational tools to efficiently quantify the microscopic fluidity and density of liquid-condensates/solid-aggregates and the temperature-dependent phase diagram of peptides. Utilizing our approaches, we comprehensively predict the LLPS abilities of all 400 dipeptide combinations of coded amino acids based on 492 micro-second molecular dynamics simulations, and observe the occurrences of spontaneous LLPS. We identify 54 dipeptides that form solid-like aggregates and three categories of dipeptides with high LLPS propensity. Our predictions are validated by turbidity assays and differential interference contrast (DIC) microscopy on four representative dipeptides (WW, QW, GF, and VI). Phase coexistence diagrams are constructed to explore the temperature dependence of LLPS. Our results reveal that aromatic moieties are crucial for a dipeptide to undergo LLPS, and hydrophobic and polar components are indispensable. We demonstrate for the first time that dipeptides, minimal but complete, possess multivalent interactions sufficient for LLPS, suggesting that LLPS is a general property of peptides/proteins, independent of their sequence length. This study provides a computational and experimental approach to the prediction and characterization of the phase behavior of minimalistic peptides, and will be helpful for understanding the sequence-dependence and molecular mechanism of protein phase separation.SignificanceProtein liquid-liquid phase separation (LLPS) is associated with human health and diseases. Identifying the minimalistic building blocks and sequence determinants of LLPS is of urgent importance but remains computationally challenging partially due to the lack of methodologies characterizing the liquid condensates. Herein we provide approaches to evaluate LLPS ability of dipeptides, and screen all 400 dipeptides by MD simulations combined with multi-bead-per-residue models which capture key interactions driving LLPS that are missing in one-bead-per-residue models. Three categories of LLPS dipeptides are identified and the experimentally-verified QW dipeptide is by far the smallest LLPS system. Our results suggest that dipeptides, minimal but complete, possess multivalent interactions sufficient for LLPS, and LLPS is a general property of peptides/proteins, independent of their length.
THEM6-mediated lipid remodelling sustains stress resistance in cancer
Authors: Blomme Arnaud , Peter Coralie , Mui Ernest , Blanco Giovanny Rodriguez , Mason Louise M. , Jamieson Lauren E. , McGregor Grace H. , Lilla Sergio , Ntala Chara , Patel Rachana , Thiry Marc , Kung Sonia H. Y. , Ford Catriona A. , Rushworth Linda K. , McGarry David J. , Mason Susan , Repiscak Peter , Nixon Colin , Salji Mark J. , Markert Elke , MacKay Gillian M. , Kamphorst Jurre J. , Graham Duncan , Faulds Karen , Fazli Ladan , Gleave Martin E. , Avezov Edward , Edwards Joanne , Yin Huabing , Sumpton David , Blyth Karen , Close Pierre , Murphy Daniel J. , Zanivan Sara , Leung Hing Y. 
Published: April 2021

ABSTRACTDespite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reducesin vivotumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. Consequently, THEM6 loss in CRPC cells significantly alters ER function, reducingde novosterol biosynthesis and preventing lipid-mediated induction of ATF4. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether, our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.
Detection of two CAL.20C SARS-CoV-2 variants in Monterrey metropolitan area in Northeast Mexico
Authors: Galán-Huerta Kame A. , Rivas-Estilla Ana M. , Lozano-Sepúlveda Sonia A. , Martínez-Acuña Natalia , Arellanos-Soto Daniel , Montes-de-Oca-Luna Roberto , Treviño-Garza Consuelo , de-la-O-Cavazos Manuel E. , Ramos-Jiménez Javier 
Published: April 2021

AbstractSARS-CoV-2 variants of concern (VOC) are a worldwide problem. CAL.20C is considered a VOC and its distribution should be monitored. We detected two CAL.20C variants in Monterrey, Mexico in patients who had no recent travel history. This indicates that this variant is now transmitted locally in Northeast Mexico.
Strategies for antigen testing: An alternative approach to widespread PCR testing
Authors: Reddy Sanjay G. , Das Saumya 
Published: April 2021

ABSTRACTMultiple applications of low cost and rapid antigen tests for individuals, in parallel (at the same time) or at times sufficiently close to each other, when appropriately interpreted can considerably increase sensitivity of these tests, improving on their performance greatly. Under reasonable assumptions, this occurs when considering a positive to arise in a composite test if at least one of two underlying repeated tests are positive. Parallel Rapid Testing can potentially provide a form of testing that is accessible (combining wide availability and lack of expense) and quick. Moreover, it can provide a level of sensitivity that is comparable to seemingly more sophisticated but more expensive alternatives. In combination with sequential testing, this strategy offers an alternative method of testing that can be applied immediately and on a widespread basis.
Impact of HIV Infection on COVID-19 Outcomes Among Hospitalized Adults in the U.S.
Authors: Durstenfeld Matthew S. , Sun Kaiwen , Ma Yifei , Rodriguez Fatima , Secemsky Eric A. , Parikh Rushi V. , Hsue Priscilla Y. 
Published: April 2021

AbstractBackgroundWhether HIV infection is associated with differences in clinical outcomes among people hospitalized with COVID-19 is uncertain.ObjectiveTo evaluate the impact of HIV infection on COVID-19 outcomes among hospitalized patients.MethodsUsing the American Heart Association’s COVID-19 Cardiovascular Disease registry, we used hierarchical mixed effects models to assess the association of HIV with in-hospital mortality accounting for patient demographics and comorbidities and clustering by hospital. Secondary outcomes included major adverse cardiac events (MACE), severity of illness, and length of stay (LOS).ResultsThe registry included 21,528 hospitalization records of people with confirmed COVID-19 from 107 hospitals in 2020, including 220 people living with HIV (PLWH). PLWH were younger (56.0+/-13.0 versus 61.3+/-17.9 years old) and more likely to be male (72.3% vs 52.7%), Non-Hispanic Black (51.4% vs 25.4%), on Medicaid (44.5% vs 24.5), and active tobacco users (12.7% versus 6.5%).Of the study population, 36 PLWH (16.4%) had in-hospital mortality compared with 3,290 (15.4%) without HIV (Risk ratio 1.06, 95%CI 0.79-1.43; risk difference 0.9%, 95%CI −4.2 to 6.1%; p=0.71). After adjustment for age, sex, race, and insurance, HIV was not associated with in-hospital mortality (aOR 1.13; 95%CI 0.77-1.6; p 0.54) even after adding body mass index and comorbidities (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91), severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86), or LOS (aOR 1.03; 95% CI 0.76-1.66, p=0.21).ConclusionHIV was not associated with adverse outcomes of COVID-19 including in-hospital mortality, MACE, or severity of illness.Condensed AbstractWe studied 21,528 patients hospitalized with COVID-19 at 107 hospitals in AHA’s COVID-19 registry to examine the association between HIV and COVID-19 outcomes. More patients with HIV were younger, male, non-Hispanic Black, on Medicaid and current smokers. HIV was not associated with worse COVID-19 in-hospital mortality (Risk ratio 1.06, 95%CI 0.79-1.43; p=0.71) even after adjustment (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was also not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91) or severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86. Our findings do not support that HIV is a major risk factor for adverse COVID-19 outcomes.
Patient perspectives on healthcare at the time of COVID-19 and suggestions for care redesign after the pandemic: a qualitative study in all six WHO regions
Authors: Stamm Tanja A , Seidler Yuki , Andrews Margaret R , Eghbali Mohammad , Kiguli Juliet , Ritschl Valentin , Omara Maisa , Schaffer Gertraud , Mosor Erika 
Published: April 2021

AbstractObjectiveThe COVID-19 pandemic has triggered significant changes in healthcare. As they were mainly driven by professionals and are likely to influence healthcare in the future, it is of utmost importance to consider patients’ perspectives equally. We, therefore, explored the lived experiences of patients and patient representatives in all six World Health Organisation (WHO) regions regarding healthcare at the time of COVID-19 and extracted suggestions for care redesign after the pandemic.MethodsWe conducted semi-structured interviews until saturation. Thematic analysis followed a modified form of meaning condensation. We established rigour by transcript checking, inter-coder agreement, quote variation and standardised reporting.ResultsDisadvantaged people experienced an unprecedented inequity in healthcare due to the pandemic. The main reasons were the reduction in public care services and limited access to information, transportation, technology and income. Stigmatisation from COVID-19 differed between cultural contexts and ranged from none to feeling “ashamed” and “totally bashed”. Participants experienced telehealth as indispensable but with limitations. These included giving “bad news”, such as having an eye removed because of melanoma, and the difficulty of providing end-of-life care over the phone. Patient representatives redefined their role and became indispensable influencers throughout the pandemic and beyond.ConclusionWe reached out to individuals with a diversity of perspectives, including minorities and marginalised populations. A systematic exclusion of people with limited technology access increases inequity in healthcare and biases research findings. Since preferences and personal meanings drive behaviour and could be foundations for targeted interventions, they must be considered in all groups of people to increase society’s resilience as a whole.
Using the OHDSI network to develop and externally validate a patient-level prediction model for Heart Failure in Type II Diabetes Mellitus
Authors: Williams Ross D. , Reps Jenna M. , Kors Jan A , Ryan Patrick B , Steyerberg Ewout , Verhamme Katia M. , Rijnbeek Peter R. 
Published: April 2021

AbstractIntroductionHeart Failure (HF) and Type 2 Diabetes Mellitus (T2DM) frequently coexist and exacerbate symptoms of each other. Treatments are available for T2DM that also provide beneficial treatment effects for HF. Guidelines recommend that patients with HF should be given Sodium-glucose co-transporter-2 inhibitors in preference to other second-line treatments for T2DM. Increasing personalization of treatment means that patients who have or are at risk of HF receive a customised treatment. We aimed to develop and externally validate prediction models to predict the 1-year risk of incident HF in T2DM patients starting second-line treatment.MethodsWe analysed a federated network of electronic medical records and administrative claims data from five databases (CCAE, MDCD, MDCR, Optum Clinformatics and Optum EHR) in the United States. We used each database to develop a model to predict 1-year risk of incident HF in patients initialising a second pharmaceutical intervention, following initial treatment with metformin for T2DM. We then performed internal validation for each model as well as external validation using the other databases.ResultsA total of 403,187 patients were included in the study. We developed 5 models with discrimination ranging from 0.72 to 0.80 at external validation in the other databases. Consistent high performance was noted for models developed in CCAE, Optum Clinformatics and Optum EHR with AUCs ranging from 0.74 to 0.81. For these models, calibration was acceptable.ConclusionThree high-performing prediction models were developed for this problem. The CCAE developed model was selected for recommendation as it achieved the same discrimination and better calibration performance than the Optum Clinformatics and Optum EHR models, whilst selecting fewer covariates and as such was selected as the best developed model. The models could be useful in stratifying patient treatment, planning healthcare utilization and reducing cost by aiding in increasing preparedness of healthcare providers.
Transcriptome analysis reveals regulatory networks and hub genes in flavonoid metabolism ofRosa roxburghii
Authors: Huang Xiaolong , Wu Zongmin , Liu Yanjing , Yi Yin , Yan Huiqing , Li Qiaohong 
Published: April 2021

ABSTRACTRosa roxburghiiTratt, the most popular fruit that blooms in the southwest of China, is rich in flavonoids. However, the regulatory network and critical genes involved in the metabolism of flavonoid compounds inR. roxburghiiare still unknown. In this study, we revealed that flavonoid, anthocyanin and catechin accumulated at different levels in various tissues ofR. roxburghii. We further obtained and analyzed differentially expressed genes (DEGs) involved in flavonoid metabolism from five samples ofR. roxburghiiby transcriptome sequencing. A total of 1 130 DEGs were identified, including 166 flavonoid pathway biosynthesis genes, 622 transcription factors, 301 transporters, and 221 cytochrome P450 proteins. A weighted gene co-expression network analysis (WGCNA) of the DEGs uncovered different co-expression networks. In terms of biosynthesis enzymes, cytochrome P450 CYP749A22 and CYP72A219 were highlighted in regulation flavonoids content. Anthocyanin 3-O-glucosyltransferase and F3’H were the top two critical enzymes for anthocyanin content. In contrast, caffeic acid 3-O-methyltransferase, 4-coumarate-CoA ligase, and shikimate O-hydroxycinnamoyl transferase were essential for catechin accumulation. Additionally, the eigengene network of the “black” module had high correlations with total flavonoid (r= 0.9, p=5e-06). There were 26 eigengenes in the “black” module, including six flavonoid biosynthesis, 14 TFs and six transporters. Among them, besides cytochrome P450 proteins (DN136557_c0_g1,DN135573_c0_g1andDN145971_c4_g1), isoflavone-hydroxylase (DN143321_c3_g1) was crucial for total flavonoids content based on the high degree of connectivity. The transcription factorsRrWRKY45(DN142829_c1_g5),RrTCP20(DN146443_c1_g1) andRrERF118(DN141507_c3_g2) were significantly correlated with flavonoids inR. roxburghii. The present transcriptomic and biochemical data on metabolites should encourage further investigation on functional genomics and breeding ofR. roxburghiiwith strong pharmaceutical potential.
Host Factor Rab11a is Critical for Efficient Assembly of Influenza A Virus Genomic Segments
Authors: Han Julianna , Ganti Ketaki , Sali Veeresh Kumar , Twigg Carly , Zhang Yifeng , Manivasagam Senthamizharasi , Liang Chieh-Yu , Vogel Olivia , Huang Iris , Emmanuel Shanan , Plung Jesse , Radoshevich Lillianna , Perez Jasmine T. , Lowen Anice C. , Manicassamy Balaji 
Published: April 2021

SummaryIt is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion; however, the role of host factors in genome assembly is not completely understood. To evaluate the significance of cellular factors in genome assembly, we generated a reporter virus carrying a tetracysteine tag in the NP gene (NP-Tc virus) and assessed the dynamics of vRNP localization with cellular components by fluorescence microscopy. At early time points, vRNP complexes were preferentially exported to the MTOC; subsequently, vRNPs associated on vesicles positive for cellular factor Rab11a and formed distinct vRNP bundles that trafficked to the plasma membrane on microtubule networks. In Rab11a deficient cells, however, vRNP bundles were smaller in the cytoplasm with less co-localization between different vRNP segments. Furthermore, Rab11a deficiency increased the production of non-infectious particles with higher RNA copy number to PFU ratios, indicative of defects in specific genome assembly. These results indicate that Rab11a+ vesicles serve as hubs for the congregation of vRNP complexes and enable specific genome assembly through vRNP:vRNP interactions, revealing the importance of Rab11a as a critical host factor for influenza A virus genome assembly.