bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the N- and C-terminal regions of FliF, the MS ring component inVibrioflagellar basal body
Authors: Kojima Seiji , Kajino Hiroki , Hirano Keiichi , Inoue Yuna , Terashima Hiroyuki , Homma Michio 
Published: January 2021

AbstractThe MS ring is a part of the flagellar basal body and formed by 34 subunits of FliF, which consists of a large periplasmic region and two transmembrane segments connected to the N- and C-terminal regions facing the cytoplasm. A cytoplasmic protein, FlhF, which determines the position and number of the basal body, supports MS ring formation in the membrane. In this study, we constructed FliF deletion mutants that lack 30 or 50 residues at the N-terminus (ΔN30 and ΔN50), and 83 (ΔC83) or 110 residues (ΔC110) at the C-terminus. The N-terminal deletions were functional and conferred motility ofVibriocells, whereas the C-terminal deletions were nonfunctional. The mutants were expressed inEscherichia colito determine whether an MS ring could still be assembled. When co-expressing ΔN30FliF or ΔN50FliF with FlhF, fewer MS rings were observed than with the expression of wild-type FliF, in the MS ring fraction, suggesting that the N-terminus interacts with FlhF. MS ring formation is probably inefficient without an additional factor or FlhF. The deletion of the C-terminal cytoplasmic region did not affect the ability of FliF to form an MS ring because a similar number of MS rings were observed for ΔC83FliF as with wild-type FliF, although further deletion of the second transmembrane segment (ΔC110FliF) abolished it. These results suggest that the terminal regions of FliF have distinct roles; the N-terminal region for efficient MS ring formation and the C-terminal region for MS ring function. The second transmembrane segment is indispensable for MS ring assembly.ImportanceThe bacterial flagellum is a supramolecular architecture involved in cell motility. At the base of the flagella, a rotary motor that begins to construct an MS ring in the cytoplasmic membrane comprises 34 transmembrane proteins (FliF). Here, we investigated the roles of the N and C terminal regions of FliF, which are MS rings. Unexpectedly, the cytoplasmic regions of FliF are not indispensable for the formation of the MS ring, but the N-terminus appears to assist in ring formation through recruitment of FlhF, which is essential for flagellar formation. The C-terminus is essential for motor formation or function.
SARS-CoV-2 seroprevalence in the urban population of Qatar: An analysis of antibody testing on a sample of 112,941 individuals
Authors: Coyle Peter V. , Chemaitelly Hiam , Hadj Kacem Mohamed Ali Ben , Al Molawi Naema Hassan Abdulla , Kahlout Reham Awni El , Gilliani Imtiaz , Younes Nourah , Kanaani Zaina Al , Khal Abdullatif Al , Kuwari Einas Al , Butt Adeel A. , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Rahim Hanan F. Abdul , Nasrallah Gheyath K. , Yassine Hadi M. , Kuwari Mohamed G. Al , Romaihi Hamad Eid Al , Al-Thani Mohamed H. , Bertollini Roberto , Abu-Raddad Laith J. 
Published: January 2021

ABSTRACTBackgroundQatar has experienced a large SARS-CoV-2 epidemic. Our first objective was to assess the proportion of the urban population that has been infected with SARS-CoV-2, by measuring the prevalence of detectable antibodies. Our second objective was to identify predictors for infection and for having higher antibody titers.MethodsResidual blood specimens from individuals receiving routine and other clinical care between May 12-September 9, 2020 were tested for anti-SARS-CoV-2 antibodies. Associations with seropositivity and higher antibody titers were identified through regression analyses. Probability weights were applied in deriving the epidemiological measures.ResultsWe tested 112,941 individuals (∼10% of Qatar’s urban population), of whom 51.6% were men and 66.0% were 20-49 years of age. Seropositivity was 13.3% (95% CI: 13.1-13.6%) and was significantly associated with sex, age, nationality, clinical-care type, and testing date. The proportion with higher antibody titers varied by age, nationality, clinical-care type, and testing date. There was a strong correlation between higher antibody titers and seroprevalence in each nationality, with a Pearson correlation coefficient of 0.85 (95% CI: 0.47-0.96), suggesting that higher antibody titers may indicate repeated exposure to the virus. The percentage of antibody-positive persons with prior PCR-confirmed diagnosis was 47.1% (95% CI: 46.1-48.2%), severity rate was 3.9% (95% CI: 3.7-4.2%), criticality rate was 1.3% (95% CI: 1.1-1.4%), and fatality rate was 0.3% (95% CI: 0.2-0.3%).ConclusionsFewer than two in every 10 individuals in Qatar’s urban population had detectable antibodies against SARS-CoV-2 between May 12-September 9, 2020, suggesting that this population is still far from the herd immunity threshold and at risk from a subsequent epidemic wave.
Leveraging mathematical models of disease dynamics and machine learning to improve development of novel malaria interventions
Authors: Golumbeanu Monica , Yang Guojing , Camponovo Flavia , Stuckey Erin M. , Hamon Nicholas , Mondy Mathias , Rees Sarah , Chitnis Nakul , Cameron Ewan , Penny Melissa A. 
Published: January 2021

AbstractBackgroundSubstantial research is underway to develop next-generation interventions that address current malaria control challenges. As there is limited testing in their early development, it is difficult to predefine intervention properties such as efficacy that achieve target health goals, and therefore challenging to prioritize selection of novel candidate interventions. Here, we present a quantitative approach to guide intervention development using mathematical models of malaria dynamics coupled with machine learning. Our analysis identifies requirements of efficacy, coverage, and duration of effect for five novel malaria interventions to achieve targeted reductions in malaria prevalence. This study highlights the role of mathematical models to support intervention development.MethodsA mathematical model of malaria transmission dynamics is used to simulate deployment and predict potential impact of new malaria interventions by considering operational, health-system, population, and disease characteristics. Our method relies on consultation with product development stakeholders to define the putative space of novel intervention specifications. We couple the disease model with machine learning to search this multi-dimensional space and efficiently identify optimal intervention properties that achieve specified health goals. We demonstrate the power of our approach by application to five malaria interventions in development.ResultsAiming for malaria prevalence reduction, we identify and quantify key determinants of intervention impact along with their minimal properties required to achieve the desired health goals. While coverage is generally identified as the largest driver of impact, higher efficacy, longer protection duration or multiple deployments per year are needed to increase prevalence reduction. We show that the efficacy and duration needs depend on the biological action of the interventions. Interventions on multiple parasite or vector targets, as well as combinations the new interventions with drug treatment, lead to significant burden reductions and lower efficacy or duration requirements.ConclusionsOur approach uses disease dynamic models and machine learning to support decision-making and resource investment, facilitating development of new malaria interventions. By evaluating the intervention capabilities in relation to the targeted health goal, our analysis allows prioritization of interventions and of their specifications from an early stage in development, and subsequent investments to be channeled cost-effectively towards impact maximization. Although we focus on five malaria interventions, the analysis is generalizable to other new malaria interventions.
Cholesteryl Hemiazelate Induces Lysosome Dysfunction and Exocytosis in Macrophages
Authors: Domingues Neuza , Almeida Calado Rita Diogo , Brito Patrícia H. , Matthiesen Rune , Ramalho José , Soares Maria I. L. , Pereira Telmo , Oliveira Luis , Vicente José R. , Wong Louise H. , Cho Soo Min , Simões Ines C. M. , Sampaio Julio , Klose Christian , Surma Michal A. , Almeida Manuel S. , Rodrigues Gustavo , Araújo-Gonçalves Pedro , Ferreira Jorge , Simons Kai , Pinho e Melo Teresa M. V. D. , Peden Andrew , Almeida Claudia Guimas , Futter Clare E. , Futerman Anthony H. , Vaz Winchil L.C. , Vieira Otilia V. 
Published: January 2021

ABSTRACTOBJECTIVEA key event in atherogenesis is the formation of lipid-loaded macrophages, lipidotic cells, which exhibit irreversible accumulation of undigested modified low-density lipoproteins in lysosomes. This event culminates with the loss of cell homeostasis, inflammation and cell death. In this study we propose to identify the chemical etiological factors and understanding the molecular and cellular mechanisms responsible for the impairment of lysosome function in macrophages.APPROACH AND RESULTSUsing shotgun lipidomics we have discovered that a family of oxidized lipids (cholesteryl hemiesters, ChE), end products of oxidation of polyunsaturated cholesteryl esters, occurs at higher concentrations in the plasma of two cohorts of cardiovascular disease patients than in the plasma of a control cohort. Macrophages exposed to the most prevalent ChE, cholesteryl hemiazelate (ChA) exhibit lysosome enlargement, peripheral lysosomal positioning, lysosome dysfunction and lipidosis which are irreversible. The transcriptomic profile of macrophages exposed to ChA indicates that the lysosome pathway is deeply affected and is well correlated with lysosome phenotypic and functional changes. Interestingly, the dysfunctional peripheral lysosomes are more prone to fuse with the plasma membrane, secreting their undigested luminal content into the extracellular milieu with potential consequences to the pathology.CONCLUSIONWe identify ChA not only as one of the molecules involved in the etiology of irreversible lysosome dysfunction culminating with lipidosis but also as a promoter of exocytosis of the dysfunctional lysosomes. The latter event is a new mechanism that may be important in the pathogenesis of atherosclerosis.
EMS-based mutants are useful for enhancing drought tolerance in spring wheat
Authors: Zahra Sadaf , Zulfiqar Sana , Hussain Momina , Akhtar Muhammad , Shaheen Tayyaba , Mehboob-ur-Rahman  
Published: January 2021

AbstractSustainable wheat production in drought prone areas can be achieved by developing resilient wheat varieties. In the present study, chemical mutagenesis was used to induce mutations in a cultivated wheat variety ‘NN-Gandum-1’. In total, 44 mutants were selected based on their high yield potential for exposing to well-watered (W1) and rainfed (W2) conditions for one season. Then 24 mutants were selected, and were exposed to W1and W2regimes. On the basis of least relative reduction in physiological parameters under W2regime, five mutants were selected for conducting exome capturing assays. In total, 184 SNPs were identified in nine genes (ABC transporter type 1, Aspartic peptidase, Cytochrome P450, transmembrane domain, Heavy metal-associated domain, HMA, NAC domain, NAD (P)-binding domain, S-type anion channel, Ubiquitin-conjugating enzyme E2 and UDP-glucuronosyl/UDP-glucosyltransferase). Maximum number of mutations were observed in chr.2D, which contained mutations in three genes i.e. ABC transporter type 1, NAD (P)-binding domain and UDP-glucuronosyl/UDP-glucosyltransferase which may have a role in conferring drought tolerance. The selected mutants were further tested for studying their biochemical responses under both the regimes for two years. The extent of membrane damage was estimated through malondialdehydeand hydrogen per oxidase and tolerance to drought stress was assessed via antioxidant enzymes in leaves. The selected mutants under drought stress increased the accumulation of proline content, total soluble sugars, total free amino acids, while decreased total chlorophyll content, carotenoids and total soluble protein. Finally, the procedure of narrowing down the number of developed mutants from a large mutation population (>4000) is found useful for exploring the complex trait like drought without compromising yield potential. These mutants can further be explored to understand the genetic circuits of drought tolerance in wheat which will pave the way towards improving livelihood of resource poor farming community mostly relying on cereal food.
Plasmodium falciparumK13 mutations in Africa and Asia present varying degrees of artemisinin resistance and an elevated fitness cost in African parasites
Authors: Stokes Barbara H. , Rubiano Kelly , Dhingra Satish K. , Mok Sachel , Straimer Judith , Gnädig Nina F. , Bath Jade R. , Deni Ioanna , Ward Kurt E. , Striepen Josefine , Yeo Tomas , Ross Leila S. , Legrand Eric , Ariey Frédéric , Cunningham Clark H. , Souleymane Issa M. , Gansané Adama , Nzoumbou-Boko Romaric , Ndayikunda Claudette , Kabanywanyi Abdunoor M. , Uwimana Aline , Smith Samuel J. , Kolley Olimatou , Ndounga Mathieu , Warsame Marian , Leang Rithea , Nosten François , Anderson Timothy J.C. , Rosenthal Philip J. , Ménard Didier , Fidock David A. 
Published: January 2021

AbstractThe emergence of artemisinin (ART) resistance inPlasmodium falciparumparasites has led to increasing rates of treatment failure with first-line ART-based combination therapies (ACTs) in Southeast Asia. In this region, select mutations in K13 can result in delayed parasite clearance ratesin vivoand enhanced survival in the ring-stage survival assay (RSA)in vitro. Our genotyping of 3,299P. falciparumisolates across 11 sub-Saharan countries reveals the continuing dominance of wild-type K13 and confirms the emergence of a K13 R561H variant in Rwanda. Using gene editing, we provide definitive evidence that this mutation, along with M579I and C580Y, can confer variable degrees ofin vitroART resistance in AfricanP. falciparumstrains. C580Y and M579I were both associated with substantial fitness costs in African parasites, which may counter-select against their dissemination in high-transmission settings. We also report the impact of multiple K13 mutations, including the predominant variant C580Y, on RSA survival rates and fitness in multiple Southeast Asian strains. No change in ART susceptibility was observed upon editing point mutations in ferrodoxin or mdr2, earlier associated with ART resistance in Southeast Asia. These data point to the lack of an evident biological barrier to mutant K13 mediating ART resistance in Africa, while identifying their detrimental impact on parasite growth.
Mapping the dynamic transfer functions of epigenome editing
Authors: Lee Jessica B. , Caywood Leandra M. , Lo Jennifer Y. , Levering Nicholas , Keung Albert J. 
Published: January 2021

AbstractBiological information can be encoded in the dynamics of signaling components which has been implicated in a broad range of physiological processes including stress response, oncogenesis, and stem cell differentiation. To study the complexity of information transfer across the eukaryotic promoter, we screened 119 dynamic conditions—modulating the frequency, intensity, and pulse width of light—regulating the binding of an epigenome editor to a fluorescent reporter. This system revealed highly tunable gene expression and filtering behaviors and provided the most comprehensive quantification to date of the maximum amount of information that can be reliably transferred across a promoter as ∼1.7 bits. Using a library of over 100 orthogonal epigenome editors, we further determined that chromatin state could be used to tune mutual information and expression levels, as well as completely alter the input-output transfer function of the promoter. This system unlocks the information-rich content of eukaryotic epigenome editing.
Facility‐specific ‘house’ microbiome ensures the maintenance of functional microbial communities into coffee beans fermentation: implications for source tracking
Authors: da Silva Vale Alexander , de Melo Pereira Gilberto Vinícius , de Carvalho Neto Dão Pedro , Sorto Ruben Dario , Goés‐Neto Aristóteles , Kato Rodrigo , Soccol Carlos Ricardo 
Published: January 2021

AbstractThis work aimed at studying the unconfirmed hypothesis predicting the existence of a connection between coffee farm microbiome and the resulting spontaneous fermentation process. Using Illumina‐based amplicon sequencing, 360 prokaryotes and 397 eukaryotes were identified from coffee fruits and leaves, over‐ripe fruits, water used for coffee de‐pulping, depulped coffee beans, soil, and temporal fermentation samples at an experimental farm in Honduras. Coffee fruits and leaves were mainly associated with high incidence of Enterobacteriaceae, Pseudomonas, Colletotrichum, and Cladosporium. The proportion of Enterobacteriaceae was increased when leaves and fruits were collected on the ground compared to those from the coffee tree. Coffee farm soil showed the richest microbial diversity with marked presence of Bacillus. Following the fermentation process, microorganisms present in depulped coffee beans (Leuconostoc, Gluconobater, Pichia, Hanseniaspora, and Candida) represented more than 90% of the total microbial community, which produced lactic acid, ethanol, and several volatile compounds. The community ecology connections described in this study showed that coffee fruit provides beneficial microorganisms for the fermentation process. Enterobacteria, Colletotrichum, and other microbial groups present in leaves, fruit surface, over‐ripe fruits, and soil may transfer unwanted aromas to coffee beans, so they should be avoided from having access to the fermentation tank.
Alarming decline of bovids in Kasanka National Park, Zambia: A case study of the puku antelope (Kobus vardonii)
Authors: Rduch Vera , Jentke Thalia 
Published: January 2021

AbstractKnowledge about antelope populations and their status is a key for conservation. In November 2019, we used distance sampling to perform a re‐survey of the bovid species in Kasanka National Park, Zambia, with a focus on the puku (Kobus vardonii). Data collection and subsequent analyses were of the same design as in a previous survey in 2009–2010. This allowed for the direct comparison between survey periods, especially for the data collected in November 2010 and 2019. The estimated puku population size decreased from 5,038 (range 3,268–7,238) animals in 2009–2010 to 819 (range 250–2,708) animals in 2019, representing an 84% decline. Smaller group sizes were observed. Changes in population structure (decline in male abundance, fewer male groups) and spatial distribution (decline in population density, especially along the park boundaries) of puku showed signs of increased poaching activities in Kasanka National Park. Also, puku became more vigilant and demonstrated significantly longer flight distances in 2019 in comparison with 2010. A strong decline in puku in combination with clear signs of poaching, as well as the reduced species richness and sightings of other bovids, should become an agenda for long‐term conservation of Kasanka National Park.
Ultraviolet filters in sunscreens and cosmetic products—A market survey
Authors: Chaiyabutr Chayada , Sukakul Thanisorn , Kumpangsin Titinun , Bunyavaree Monthatip , Charoenpipatsin Norramon , Wongdama Supisara , Boonchai Waranya 
Published: January 2021

AbstractBackgroundAs several reports have raised a variety of environmental, health, and safety issues related to ultraviolet (UV) filters, it is crucial to understand the trends in the exposure of the population to UV filters.ObjectiveTo determine the frequency of UV filter usage in sunscreens and other cosmetic products in Thai market.MethodsWe surveyed the UV filter labelling on sunscreens and cosmetic products sold in the Thai market. In all, 312 sunscreens and 1350 other cosmetic products were investigated.ResultsTitanium dioxide was the most frequently used UV filter in both sunscreens (66.7%) and other cosmetic products (68.4%). Ethylhexyl methoxycinnamate was the most common organic UVB filter, whereas butyl methoxydibenzoylmethane was the most common organic UVA filter. In sunscreens aimed at children, bis‐ethylhexyloxyphenol methoxyphenyl triazine was the most commonly used UV filter. The most frequent co‐occurrence of UV filters was titanium dioxide and ethylhexyl methoxycinnamate.ConclusionsTitanium dioxide was the most commonly used UV filter, which differs from the findings of previous surveys. Knowing the availability and frequency of each UV filter provides valuable information about consumer exposure levels, facilitates refinements of the allergen series in patch testing, and enhances the monitoring of adverse effects of UV filters.
Persistence of both reversible airway obstruction and higher blood eosinophils may predict lung function decline in severe asthma
Authors: Sposato Bruno , Scalese Marco , Ricci Alberto , Rogliani Paola , Paggiaro Pierluigi ,   The Omalizumab Italian Study Group
Published: January 2021

AbstractObjectiveThis study analysed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics.MethodsAbout 202 severe asthmatics were studied after 12–120 months of step‐5 treatment associated to anti‐IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV1 > 12% or ≤12% changes differentiated RAO+ from RAO− subjects. Blood eosinophil (BE) counts after treatment were considered.ResultsPre‐/post‐treatment bronchodilator FEV1% and ACT were lower (61% [50–71], 74.4% [62.5–83.7] and 20[18–22]), whereas BE were higher (380 cells/µl [170–590]) in RAO+ compared to RAO− subjects (77% [64–88], p = 0.0001, 81.8% [66.1–94.3], p = 0.0001, 21[18–23], p = 0.045 and 230 cells/µl [80–360], p = 0.003). A negative relationship between SABA‐induced FEV1% changes and pre‐bronchodilator FEV1% (β = −0.551%; p = 0.0001) and ACT (β = −0.059; p = 0.038) was found. Conversely, post‐treatment BE levels were positively related (β = 145.565 cells/µl; p = 0.003) to FEV1 > 12% increases. A rising trend of pre‐/post‐bronchodilator FEV1% in time was observed in RAO− subjects with BE < 300 cells/µl. Conversely, we highlighted significant declining tendencies of pre/post‐bronchodilator FEV1% in RAO+ patients with BE > 300 cells/µl reaching lower values after more than 36 months of step‐5 treatment (59.6% [39.9–72.1] vs 74[66.5–89.2] of RAO+ individuals with BE < 300 cells/µl [p = 0.026] and 81.6% [66.1–91.8] of RAO‐subjects with BE > 300 cells/µl [p = 0.009]).ConclusionPersistent SABA‐induced FEV1 > 12%, especially when associated to BE > 300 cells/ml, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step‐5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline.