bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and genotyping of Echinococcus granulosus sensu lato from livestock in north-eastern Kenya
Authors: Omondi H.A. , Gitau G. , Gathura P. , Mulinge E. , Zeyhle E. , Kimeli P. , Bett B.
Published: October 2020

Cystic echinococcosis (CE) is a zoonotic disease of cosmopolitan distribution and caused by the larval stage of the dog tapeworm, Echinococcus granulosus sensu lato (s.l.). CE occurs in the wider African continent and in Kenya, notably in the Maasailand and Turkana regions; however, recent studies demonstrate its presence in other parts of Kenya. This study determined the occurrence of CE in livestock (camels, goats, sheep and cattle) in Isiolo, Garissa and Wajir counties, and characterized the species of E. granulosus s.l. present. An abattoir survey was used to determine the presence of CE in various organs in livestock. Polymerase chain reaction-restriction fragment length polymorphism and sequencing of the mitochondrial NADH dehydrogenase subunit 1 gene was used for genotyping. A total of 1368 carcasses from 687 goats, 234 camels, 329 sheep and 118 cattle were inspected for the presence of hydatid cysts. The overall proportion of infections was 29.1% in camels, 14.4% in cattle, 9.9% in goats and 8.2% in sheep. The liver was the most infected organ, while only the lung of camels harboured fertile cysts. Of the 139 cysts genotyped, 111 (79.9%) belonged to Echinococcus canadensis (G6/7) and 20 (14.4%) to E. granulosus sensu stricto. One and two cysts were identified as Taenia saginata and unknown Taenia species, respectively. There was a significant association between county of origin and species of the animal with occurrence of CE. This study reports, for the first time, the characterization of Echinococcus species in livestock from Garissa and Wajir counties, and the current situation in Isiolo county. The fertility of cysts in camels and frequency of E. canadensis (G6/7) in all livestock species indicate that camels play an important role in the maintenance of CE in the north-eastern counties of Kenya.
Reproductive compensation in female Palaemonetes argentinus (Decapoda: Natantia) due to Microphallus szidati (Trematoda) infection
Authors: Parietti M. , Merlo M.J. , Natal M. , Méndez Casariego M.A.
Published: October 2020

Parasites may affect host demographic characteristics because they can directly or indirectly cause the death of their hosts and/or influence their reproduction. Parasitism is therefore recognized as a factor that influences the composition and structure of populations and communities. One of these behaviours is the compensatory response: the host can compensate for the parasite losses effect, modifying the reproductive effort to enhance fitness. Ovigerus female Palaemonetes argentinus was collected and sorted into two groups according to the degree of development of their embryos: newly spawned embryos and embryos ready to hatch. The number of embryos and their dry weight for each female were determined. All parts of the female body were checked for parasites. The females of P. argentinus were parasitized by Microphalus szidati. We found that parasitized females produce more embryos but had more egg loss during development and the percentage of embryonic loss was higher in the parasitized females than in non-parasitized. Parasitized females produced lighter eggs than those from uninfected females. This supports the compensatory reproduction hypothesis suggested for this species. Parasitism can change life history traits in a way that fecundity can be compensated; this co-evolution between host and parasites will be population or context dependent. Parasites are a functional part of any ecosystem and as our results show, deleting parasites in life history traits and reproduction studies in free living organisms could lead to an incomplete picture of the true processes that happen in nature.
Membership categorization analysis of racism in an online discussion among neighbors
Authors: Shrikant Natasha
Published: October 2020

This article addresses relationships between micro and macro aspects of language use through analyzing online interactions among neighbors discussing racism in their neighborhood. Membership categorization analysis supplemented with critical theory highlights how the ways neighbors name, characterize, and position categories orients to their rhetorical and identity goals (to construct reasonable stances, to seem not racist), which in turn motivates alignment with critical, folk, or colorblind ideologies of racism. Thus, ideologies do not determine interactional choices participants make, but rather are constituted by those choices. Findings also illustrate how discursive strategies such as reported speech, absurdity, three-part lists, and metadiscourse support ways that neighbors organize categories and achieve their aims. Additional contributions to this study include demonstrating the utility of membership categorization analysis for analyzing discourses of racism and providing practical insight into how racially diverse groups can have productive conversations about racism. (Racism, ideology, membership categorization analysis)*
Older adults’ accounts of the relationships between retirement timing and health: a descriptive qualitative analysis in Chile
Authors: Shura Robin , Opazo Sebastian , Calvo Esteban
Published: October 2020

Retirement timing can have important health implications. Little is known, however, about older adults’ views on this issue and whether they consider it better to retire later, earlier, on time or anytime. This knowledge gap about older adults’ views is particularly true outside North America and Europe. This qualitative study aims to examine older Chileans’ ideas about the relationship between retirement timing and health and to explore gender and class patterns in qualitative themes identified, knowledge which may strengthen quantitative population-based approaches. Framework analysis was conducted on qualitative accounts from a purposive, non-random sample of 40 older Chileans in six focus groups, stratified by gender and class as marked by lifetime occupation. Transcriptions were coded by two independent reviewers (inter-coder reliability = 81%) according to four deductive categories of retirement timing as well as inductive coding of emergent themes. The content and sequence of codes were visually represented in MAXQDA's document portraits and illustrated with descriptive quotes. Results indicate that participants’ views about when to retire in order to maximise health did not highlight retirement age or timing (later, earlier, on time, anytime). Instead, these older Chileans emphasised that the optimal retirement age depends on other conditions, such as employment quality, retirement income and gender. These views were patterned: lower occupational-class participants emphasised income and job hazards, higher-class males emphasised job satisfaction and higher-class females emphasised gendered patterns. Women and lower-class participants were relatively more favourable to earlier retirements than men and higher-class participants. Overall, qualitative analyses of lay perspectives from understudied country contexts complement and extend population-based models focused on timing or retirement age, suggest specific characteristics of retirement transitions that may moderate health consequences, and highlight class and gender differences in views of retirement timing. More research is needed using mixed-methods approaches and leveraging both purposive and random samples.
Dynamics of COVID-19 transmission including indirect transmission mechanisms: a mathematical analysis
Authors: Meiksin A.
Published: October 2020

The outbreak of the novel coronavirus severe acute respiratory syndrome-coronavirus-2 has raised major health policy questions and dilemmas. Whilst respiratory droplets are believed to be the dominant transmission mechanisms, indirect transmission may also occur through shared contact of contaminated common objects that is not directly curtailed by a lockdown. The conditions under which contaminated common objects may lead to significant spread of coronavirus disease 2019 during lockdown and its easing is examined using the susceptible-exposed-infectious-removed model with a fomite term added. Modelling the weekly death rate in the UK, a maximum-likelihood analysis finds a statistically significant fomite contribution, with 0.009 ± 0.001 (95% CI) infection-inducing fomites introduced into the environment per day per infectious person. Post-lockdown, comparison with the prediction of a corresponding counterfactual model with no fomite transmission suggests fomites, through enhancing the overall transmission rate, may have contributed to as much as 25% of the deaths following lockdown. It is suggested that adding a fomite term to more complex simulations may assist in the understanding of the spread of the illness and in making policy decisions to control it.
Unfree labour by free peasants: labour service in the Swedish and Finnish countryside, from the late seventeenth to the early twentieth centuries
Authors: Rahikainen Marjatta
Published: October 2020

This article discusses the received image of free Swedish and Finnish peasants, charting parallels with peasants in the Baltic region. It draws upon the post-Cold War discussion of free and unfree rural labour in early modern Europe. The discussion maintains that the labour service by free Swedish and Finnish peasant landholders and peasant tenants at its heaviest point may have been on a par with thecorvéein the early modern Baltic provinces. It is suggested that the Cold War mental map may have led to an overstatement of the East-West distinction between peasants’ circumstances in the Baltic Sea region.
GovernanceofandbyPhilanthropic Foundations
Authors: Engwall Lars
Published: October 2020

Philanthropic foundations have become increasingly important in present-day societies. In relation to governance, they represent some specific features. Like corporations, they are subject to regulation, but they differ by having neither owners nor customers. This makes the governanceoffoundations an important issue for study. At the same time, governancebyfoundations is likewise of importance. It includes the role of foundations in corporate governance based on their ownership in corporations and their role in resource allocation based on the returns of their assets. Against this background, this article addresses three research questions: (1) What are the characteristics of the governance of foundations? (2) What role do foundations play for corporate governance? (3) What role do foundations play for resource allocation? In order to contribute to answering these questions this article provides an analysis of the first centenary (1917−2017) of a major Swedish philanthropic foundation, the Knut and Alice Wallenberg Foundation. It is concluded that successful foundation governance is characterized by (1) rule compliance, (2) loyalty to the founders, and (3) legitimacy among prospective grantees. Additional conclusions are that the larger, the more concentrated, and the more long-term the asset portfolio, the more significant will be the role a foundation may play in corporate governance, and the more successful asset management and the more careful project selection, the more significant will be the role a foundation may play in resource allocation. In addition, the article demonstrates the reciprocal relationships between foundations, corporations, and grantees.
Is there a relationship between morphological and functional platelet changes and depressive disorder?
Authors: Tagliarini Claudia , Carbone Manuel Glauco , Pagni Giovanni , Marazziti Donatella , Pomara Nunzio
Published: October 2020

Background

Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral biomarker of neuronal activity. Therefore, the literature strongly focused on the investigation of eventual structural and functional platelet abnormalities in neuropsychiatric disorders, particularly in depressive disorder. Given their impact in biological psychiatry, the goal of the present paper was to review and critically analyze studies exploring platelet activity, functionality, and morpho-structure in subjects with depressive disorder.

Methods

According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to March 2020 with the search terms: (1)platelets in depression [Title/Abstract]”; (2) “(platelets[Title]) AND depressive disorder[Title/Abstract]”;(3)“(Platelet[Title]) AND major depressive disorder[Title]”;(4)(platelets[Title]) AND depressed[Title]”;(5)(platelets[Title]) AND depressive episode[Title]”;(6)(platelets[Title]) AND major depression[Title]”;(7)platelet activation in depression[All fields]”;and (8)platelet reactivity in depression[All fields].”

Results

After a detailed screening analysis and the application of specific selection criteria, we included in our review a total of 106 for qualitative synthesis. The studies were classified into various subparagraphs according to platelet characteristics analyzed: serotonergic system (5-HT2Areceptors, SERT activity, and 5-HT content), adrenergic system, MAO activity, biomarkers of activation, responsivity, morphological changes, and other molecular pathways.

Conclusions

Despite the large amount of the literature examined, nonunivocal and, occasionally, conflicting results emerged. However, the findings on structural and metabolic alterations, modifications in the expression of specific proteins, changes in the aggregability, or in the responsivity to different pro-activating stimuli, may be suggestive of potential platelet dysfunctions in depressed subjects, which would result in a kind of hyperreactive state. This condition could potentially lead to an increased cardiovascular risk. In line with this hypothesis, we speculated that antidepressant treatments would seem to reduce this hyperreactivity while representing a potential tool for reducing cardiovascular risk in depressed patients and, maybe, in other neuropsychiatric conditions. However, the problem of the specificity of platelet biomarkers is still at issue and would deserve to be deepened in future studies.
Using a Large‐n Seismic Array to Explore the Robustness of Spectral Estimations
Authors: Kemna K. B. , Peña Castro A. F. , Harrington R. M. , Cochran E. S.
Published: October 2020

Spectral analysis is widely used to estimate and refine earthquake source parameters such as source radius, seismic moment, and stress drop. This study aims to quantify the precision of the single spectra and empirical Green's function spectral ratio approach using the Large‐n Seismic Survey in Oklahoma (LASSO) array. The dense station coverage in an area of local saltwater disposal offers a unique opportunity to observe and quantify radiation pattern effects and subsequent precision of spectral estimates of small earthquakes (M < 3). The results suggest that the precision of source properties estimated from direct phase arrivals for arrays with less than 20 stations should be assumed to be not less than 30% and could be as high as 150% if less than five stations are used. Furthermore, we do not see clear evidence for, or against, a scaling of stress drop with magnitude of small earthquakes (M < 3) as observed by other studies.
SERMeQ Model Produces a Realistic Upper Bound on Calving Retreat for 155 Greenland Outlet Glaciers
Authors: Ultee Lizz , Bassis Jeremy N.
Published: October 2020

The rate of land ice loss due to iceberg calving is a key source of variability among model projections of the 21st century sea level rise. It is especially challenging to account for mass loss due to iceberg calving in Greenland, where ice drains to the ocean through hundreds of outlet glaciers, many smaller than typical model grid scale. Here, we apply a numerically efficient network flowline model (SERMeQ) forced by surface mass balance to simulate an upper bound on decadal calving retreat of 155 grounded outlet glaciers of the Greenland Ice Sheet—resolving five times as many outlets as was previously possible. We show that the upper bound holds for 91% of glaciers examined and that simulated changes in terminus position correlate with observed changes. SERMeQ can provide a physically consistent constraint on forward projections of the dynamic mass loss from the Greenland Ice Sheet associated with different climate projections.
Effects of Nitrogen Limitation on Phytoplankton Physiology in the Western Arctic Ocean in Summer
Authors: Ko Eunho , Gorbunov Maxim Y. , Jung Jinyoung , Joo Hyoung Min , Lee Youngju , Cho Kyoung‐Ho , Yang Eun Jin , Kang Sung‐Ho , Park Jisoo
Published: October 2020

Phytoplankton in the Arctic Ocean are subject to nitrogen limitation in the summer, however, how severely the nitrogen stress affects phytoplankton physiology remains largely unknown. In the summers of 2015–2018, we examined the distribution of phytoplankton photophysiological properties across two contrasting regions of the Arctic Ocean with distinctly different levels of nitrogen availability in the upper water column. We quantified the extent of nitrogen stress using a highly sensitive fluorescence induction and relaxation system to obtain continuous underway measurements and via discrete sample analyses of phytoplankton physiology, as well as nutrient enrichment incubations. The results revealed vast regions in the Chukchi Sea where phytoplankton photosynthesis was severely nitrogen‐stressed. Thereby, the maximum quantum yield of photochemistry in photosystem II showed only a small decrease (12 ± 9%) relative to its nutrient‐replete values, while the maximum photosynthetic electron transport rates under saturating irradiance were impaired to a greater extent (40 ± 17%). This phytoplankton photosynthesis response is indicative of a severe nitrogen limitation, which results in dramatic reduction in growth and net primary production rates. Nutrient enrichment incubations also revealed a marked increase in large‐size phytoplankton growth (>10 μm) after the nitrogen stress was alleviated, suggesting that the larger cells were more susceptible to nitrogen stress. These results are important for understanding how regional nitrogen fluxes control variability in the primary production and phytoplankton community structure and how these processes might change with rapid climate changes in the Arctic Ocean.
Spatiotemporal Variability and Driving Factors of Tibetan Plateau Water Use Efficiency
Authors: Lin Shan , Wang Genxu , Hu Zhaoyong , Huang Kewei , Sun Juying , Sun Xiangyang
Published: October 2020

Water use efficiency (WUE) provides vital information about the carbon‐water coupling relationship of a terrestrial ecosystem. Understanding the spatiotemporal variability and driving factors of the Tibetan Plateau (TP) WUE can facilitate the prediction of the response of the carbon‐water process in the TP to climate change. We used a land surface model to investigate spatiotemporal changes in WUE and the responses to environmental factors, such as atmospheric CO2 concentration and climate and land use change. Our results suggest that the average annual TP WUE was 0.38 g C kg−1 H2O and that this variable tended to increase at a rate of 0.001 g C kg−1 H2O year−1 during the period of 1979–2010. Changes in atmospheric CO2 concentration caused a significant increase in the rate of WUE change (i.e., 0.00051 g C kg−1 H2O year−1); these changes were also found to most significantly contribute to WUE increase in the TP and account for approximately 51% of the WUE fluctuation. Increasing temperature was found to result in a decreasing WUE (rate: −0.00028 g C kg−1 H2O year−1). Regarding results on vegetation type, forested areas had the highest WUE (i.e., 0.88 g C kg−1 H2O) and the highest rate of WUE change (i.e., 0.004 g C kg−1 H2O year−1), whereas the lowest WUE (i.e., 0.26 g C kg−1 H2O) was found in steppe and alpine vegetation areas. Although all other vegetation types were associated with increasing WUE, there was no significant change in the WUE of steppe areas. The main factors influencing WUE fluctuation for different vegetation types were found to be atmospheric CO2 concentration and temperature change.
Influence of Geomagnetic Activity on Derivation of Temperatures From Meteor Wind Radars
Authors: Hall C. M. , Johnsen M. G.
Published: October 2020

Echoes from meteor trails can be analyzed to derive diffusion coefficient and thereafter estimates of neutral temperatures, typically around 90 km altitude. The method entails some assumptions and, usually, use of model pressures. Even so, variations in derived temperatures have been assumed to be representative and indicators of other mesospheric processes. However, we now find that the observed variations, seen as enhancements, are very closely associated with enhancements in geomagnetic activity. Here we introduce a metric for describing geomagnetic activity (as an alternative to, e.g., the k‐index) and suggest a methodology for near‐real‐time correction of results.
The Flare Irradiance Spectral Model‐Version 2 (FISM2)
Authors: Chamberlin P. C. , Eparvier F. G. , Knoer V. , Leise H. , Pankratz A. , Snow M. , Templeman B. , Thiemann E. M. B. , Woodraska D. L. , Woods T. N.
Published: October 2020

The Flare Irradiance Spectral Model (FISM) is an important tool for estimating solar variability for a myriad of space weather research studies and applications, and FISM Version 2 (FISM2) recently was released. FISM2 is an empirical model of the solar ultraviolet irradiance created to fill spectral and temporal gaps in the satellite observations. FISM2 estimates solar ultraviolet irradiance variations due to the solar cycle, solar rotations, and solar flares. The major improvement provided by FISM2 is that it is based on multiple new, more accurate instruments that have now captured almost a full solar cycle and thousands of flares, drastically improving the accuracy of the modeled FISM2 solar irradiance spectra. Specifically, these new instruments are the Solar Dynamics Observatory (SDO)/Extreme Ultraviolet Variability Experiment (EVE), Solar Radiation and Climate Experiment (SORCE)/X‐ray Photometer System (XPS), and SORCE/Solar Stellar Irradiance Comparison Experiment (SOLSTICE). FISM2 is also improved to 0.1‐nm spectral bins across the same 0‐ to 190‐nm spectral range and is already being used in research to estimate space weather changes due to solar irradiance variability in planetary thermospheres and ionospheres.
Transit Time Distributions Estimation Exploiting Flow‐Weighted Time: Theory and Proof‐of‐Concept
Authors: Kim Minseok , Troch Peter A.
Published: October 2020

Time‐variable transit time distributions (TTDs) have been utilized as a tool to understand how catchments transmit water. However, most of the existing TTD estimation methods require to impose certain structures on those TTDs a priori, which could lead to misinterpreting data. We present a data‐based method to estimate time‐variable TTDs without imposing their structure a priori. The core of the method is the use of a revised flow‐weighted time, where TTDs do not reflect variable external forcings directly. The functional forms of the TTDs are much simpler in flow‐weighted time, compared to those in calendar time, and this allows for easier estimation of TTDs. Dynamic (state‐dependent) multiple linear regression methods were applied to estimate the time‐variable TTDs in flow‐weighted time, which can eventually be transformed back to calendar time. The method performs well in a proof‐of‐concept demonstration with synthetic data sets. We also discuss potential generalizations of the proposed method.
Transition From Viscous Fingering to Capillary Fingering: Application of GPU‐Based Fully Implicit Dynamic Pore Network Modeling
Authors: An Senyou , Erfani Hamidreza , Godinez‐Brizuela Omar E. , Niasar Vahid
Published: October 2020

Immiscible two‐phase flow through porous materials exhibits different invasion patterns controlled by dynamic conditions, competition between the viscous and capillary forces, and the contrast between the fluids viscosities. Two distinct invasion patterns are viscous and capillary fingering. While the first one happens under unfavorable viscosity ratios at high injection rates, the second one happens when the viscous forces are very small compared to the capillary forces. Depending on whether the invasion is under the capillary fingering or viscous fingering regime, the remaining oil saturation and the effective permeability of the fluids can significantly change. The contribution of the present work has two key aspects: (a) It addresses how the remaining saturation changes at different flow rates (i.e., capillary numbers) for different unfavorable viscosity ratios in a three‐dimensional system; (b) it presents a new dynamic pore network model using the fully implicit scheme which has been enhanced by the graphic processing unit (GPU) parallel computing. Additionally, the model has been carefully validated against micromodel experiments in both time and space, which to our best knowledge has not been reported in such detail in the literature. The results of the validated 3‐D dynamic pore network model demonstrate the remaining saturation at the breakthrough time as a nonmonotonic trend with the imposed capillary number.
Practical guide for managing large-scale human genome data in research
Authors: Tanjo Tomoya , Kawai Yosuke , Tokunaga Katsushi , Ogasawara Osamu , Nagasaki Masao
Published: October 2020

Studies in human genetics deal with a plethora of human genome sequencing data that are generated from specimens as well as available on public domains. With the development of various bioinformatics applications, maintaining the productivity of research, managing human genome data, and analyzing downstream data is essential. This review aims to guide struggling researchers to process and analyze these large-scale genomic data to extract relevant information for improved downstream analyses. Here, we discuss worldwide human genome projects that could be integrated into any data for improved analysis. Obtaining human whole-genome sequencing data from both data stores and processes is costly; therefore, we focus on the development of data format and software that manipulate whole-genome sequencing. Once the sequencing is complete and its format and data processing tools are selected, a computational platform is required. For the platform, we describe a multi-cloud strategy that balances between cost, performance, and customizability. A good quality published research relies on data reproducibility to ensure quality results, reusability for applications to other datasets, as well as scalability for the future increase of datasets. To solve these, we describe several key technologies developed in computer science, including workflow engine. We also discuss the ethical guidelines inevitable for human genomic data analysis that differ from model organisms. Finally, the future ideal perspective of data processing and analysis is summarized.
Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma
Authors: Kang Yuanbo , He Weihan , Ren Caiping , Qiao Jincheng , Guo Qiuyong , Hu Jingyu , Xu Hongjuan , Jiang Xingjun , Wang Lei
Published: October 2020

Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus. Based on epidemiological data, both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region, in particular, with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy (IMRT) which profoundly contributes to the cure rate of NPC patients. To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment, we discussed the implication of using targeted therapy against critical molecules in various signal pathways, and how they synergize with chemoradiotherapy in the NPC treatment. Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options, which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.
Host specificity of microbiome assembly and its fitness effects in phytoplankton
Authors: Jackrel Sara L , Yang Jinny W , Schmidt Kathryn C , Denef Vincent J
Published: October 2020

Insights into symbiosis between eukaryotic hosts and their microbiomes have shifted paradigms on what determines host fitness, ecology, and behavior. Questions remain regarding the roles of host versus environment in shaping microbiomes, and how microbiome composition affects host fitness. Using a model system in ecology, phytoplankton, we tested whether microbiomes are host-specific, confer fitness benefits that are host-specific, and remain conserved in time in their composition and fitness effects. We used an experimental approach in which hosts were cleaned of bacteria and then exposed to bacterial communities from natural environments to permit recruitment of microbiomes. We found that phytoplankton microbiomes consisted of a subset of taxa recruited from these natural environments. Microbiome recruitment was host-specific, with host species explaining more variation in microbiome composition than environment. While microbiome composition shifted and then stabilized over time, host specificity remained for dozens of generations. Microbiomes increased host fitness, but these fitness effects were host-specific for only two of the five species. The shifts in microbiome composition over time amplified fitness benefits to the hosts. Overall, this work solidifies the importance of host factors in shaping microbiomes and elucidates the temporal dynamics of microbiome compositional and fitness effects.
Correction: ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway
Authors: Chen Zhida , Wu Chunying , Liu Yuting , Li Haonan , Zhu Yeyan , Huang Cailing , Lin Huangbo , Qiao Qiao , Huang Mengming , Zhu Qing , Wang Lei
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
HCF-1 promotes cell cycle progression by regulating the expression of CDC42
Authors: Xiang Pan , Li Fei , Ma Zhihua , Yue Jiping , Lu Cailing , You Yuangang , Hou Lin , Yin Bin , Qiang Boqin , Shu Pengcheng , Peng Xiaozhong
Published: October 2020

The eukaryotic cell cycle involves a highly orchestrated series of events in which the cellular genome is replicated during a synthesis (S) phase and each of the two resulting copies are segregated properly during mitosis (M). Host cell factor-1 (HCF-1) is a transcriptional co-regulator that is essential for and has been implicated in basic cellular processes, such as transcriptional regulation and cell cycle progression. Although a series of HCF-1 transcriptional targets have been identified, few functional clues have been provided, especially for chromosome segregation. Our results showed that HCF-1 activated CDC42 expression by binding to the −881 to −575 region upstream of the CDC42 transcription start site, and the regulation of CDC42 expression by HCF-1 was correlated with cell cycle progression. The overexpression of a spontaneously cycling and constitutively active CDC42 mutant (CDC42F28L) rescued G1 phase delay and multinucleate defects in mitosis upon the loss of HCF-1. Therefore, these results establish that HCF-1 ensures proper cell cycle progression by regulating the expression of CDC42, which indicates a possible mechanism of cell cycle coordination and the regulation mode of typical Rho GTPases.
MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk
Authors: Surakka Ida , Fritsche Lars G. , Zhou Wei , Backman Joshua , Kosmicki Jack A. , Lu Haocheng , Brumpton Ben , Nielsen Jonas B. , Gabrielsen Maiken E. , Skogholt Anne Heidi , Wolford Brooke , Graham Sarah E. , Chen Y. Eugene , Lee Seunggeun , Kang Hyun Min , Langhammer Arnulf , Forsmo Siri , Åsvold Bjørn O. , Styrkarsdottir Unnur , Holm Hilma , Gudbjartsson Daniel , Stefansson Kari , Baras Aris ,   Regeneron Genetics Center, Bai Xiaodong , Balasubramanian Suganthi , Barnard Leland , Blumenfeld Andrew , Cantor Michael , Coppola Giovanni , Economides Aris , Eom Gisu , Habegger Lukas , Hahn Young , Hawes Alicia , Jones Marcus B. , Khalid Shareef , Lotta Luca A. , Maxwell Evan K. , Mitnaul Lyndon J. , Overton John D. , Reid Jeffrey G. , Ferreira Manuel Allen Revez , Salerno William , Sharma Deepika , Shuldiner Alan , Staples Jeffrey C. , Yadav Ashish , Abecasis Goncalo R. , Hveem Kristian , Willer Cristen J.
Published: October 2020

A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of the Nord-Trøndelag Health Study, followed by imputation in the remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation in MEPE, p.(Lys70IlefsTer26, minor allele frequency [MAF] = 0.8%), was associated with decreased ultradistal forearm BMD (P-value = 2.1 × 10−18), and increased osteoporosis (P-value = 4.2 × 10−5) and fracture risk (P-value = 1.6 × 10−5). The MEPE LoF association with BMD and fractures was further evaluated in 279,435 UK (MAF = 0.05%, heel bone estimated BMD P-value = 1.2 × 10−16, any fracture P-value = 0.05) and 375,984 Icelandic samples (MAF = 0.03%, arm BMD P-value = 0.12, forearm fracture P-value = 0.005). Screening for the MEPE LoF mutations before adulthood could potentially prevent osteoporosis and fractures due to the lifelong effect on BMD observed in the study. A key implication for precision medicine is that high-impact functional variants missing from the publicly available cosmopolitan panels could be clinically more relevant than polygenic risk scores.
Sources and upstream pathways of the densest overflow water in the Nordic Seas
Authors: Huang Jie , Pickart Robert S. , Huang Rui Xin , Lin Peigen , Brakstad Ailin , Xu Fanghua
Published: October 2020

Overflow water from the Nordic Seas comprises the deepest limb of the Atlantic Meridional Overturning Circulation, yet questions remain as to where it is ventilated and how it reaches the Greenland-Scotland Ridge. Here we use historical hydrographic data from 2005-2015, together with satellite altimeter data, to elucidate the source regions of the Denmark Strait and Faroe Bank Channel overflows and the pathways feeding these respective sills. A recently-developed metric is used to calculate how similar two water parcels are, based on potential density and potential spicity. This reveals that the interior of the Greenland Sea gyre is the primary wintertime source of the densest portion of both overflows. After subducting, the water progresses southward along several ridge systems towards the Greenland-Scotland Ridge. Kinematic evidence supports the inferred pathways. Extending the calculation back to the 1980s reveals that the ventilation occurred previously along the periphery of the Greenland Sea gyre.
Seasonal modulation of phytoplankton biomass in the Southern Ocean
Authors: Arteaga Lionel A. , Boss Emmanuel , Behrenfeld Michael J. , Westberry Toby K. , Sarmiento Jorge L.
Published: October 2020

Over the last ten years, satellite and geographically constrained in situ observations largely focused on the northern hemisphere have suggested that annual phytoplankton biomass cycles cannot be fully understood from environmental properties controlling phytoplankton division rates (e.g., nutrients and light), as they omit the role of ecological and environmental loss processes (e.g., grazing, viruses, sinking). Here, we use multi-year observations from a very large array of robotic drifting floats in the Southern Ocean to determine key factors governing phytoplankton biomass dynamics over the annual cycle. Our analysis reveals seasonal phytoplankton accumulation (‘blooming’) events occurring during periods of declining modeled division rates, an observation that highlights the importance of loss processes in dictating the evolution of the seasonal cycle in biomass. In the open Southern Ocean, the spring bloom magnitude is found to be greatest in areas with high dissolved iron concentrations, consistent with iron being a well-established primary limiting nutrient in this region. Under ice observations show that biomass starts increasing in early winter, well before sea ice begins to retreat. The average theoretical sensitivity of the Southern Ocean to potential changes in seasonal nutrient and light availability suggests that a 10% change in phytoplankton division rate may be associated with a 50% reduction in mean bloom magnitude and annual primary productivity, assuming simple changes in the seasonal magnitude of phytoplankton division rates. Overall, our results highlight the importance of quantifying and accounting for both division and loss processes when modeling future changes in phytoplankton biomass cycles.
Sensing of autoinducer-2 by functionally distinct receptors in prokaryotes
Authors: Zhang Lei , Li Shuyu , Liu Xiaozhen , Wang Zhuo , Jiang Mei , Wang Ruiying , Xie Laigong , Liu Qinmeng , Xie Xiaorong , Shang Daohan , Li Mengyun , Wei Zhiyan , Wang Yao , Fan Chengpeng , Luo Zhao-Qing , Shen Xihui
Published: October 2020

Autoinducer-2 (AI-2) is a quorum sensing signal that mediates communication within and between many bacterial species. However, its known receptors (LuxP and LsrB families) are not found in all the bacteria capable of responding to this signaling molecule. Here, we identify a third type of AI-2 receptor, consisting of a dCACHE domain. AI-2 binds to the dCACHE domain of chemoreceptors PctA and TlpQ of Pseudomonas aeruginosa, thus inducing chemotaxis and biofilm formation. Boron-free AI-2 is the preferred ligand for PctA and TlpQ. AI-2 also binds to the dCACHE domains of histidine kinase KinD from Bacillus subtilis and diguanylate cyclase rpHK1S-Z16 from Rhodopseudomonas palustris, enhancing their enzymatic activities. dCACHE domains (especially those belonging to a subfamily that includes the AI-2 receptors identified in the present work) are present in a large number of bacterial and archaeal proteins. Our results support the idea that AI-2 serves as a widely used signaling molecule in the coordination of cell behavior among prokaryotic species.
Increased power from conditional bacterial genome-wide association identifies macrolide resistance mutations in Neisseria gonorrhoeae
Authors: Ma Kevin C. , Mortimer Tatum D. , Duckett Marissa A. , Hicks Allison L. , Wheeler Nicole E. , Sánchez-Busó Leonor , Grad Yonatan H.
Published: October 2020

The emergence of resistance to azithromycin complicates treatment of Neisseria gonorrhoeae, the etiologic agent of gonorrhea. Substantial azithromycin resistance remains unexplained after accounting for known resistance mutations. Bacterial genome-wide association studies (GWAS) can identify novel resistance genes but must control for genetic confounders while maintaining power. Here, we show that compared to single-locus GWAS, conducting GWAS conditioned on known resistance mutations reduces the number of false positives and identifies a G70D mutation in the RplD 50S ribosomal protein L4 as significantly associated with increased azithromycin resistance (p-value = 1.08 × 10−11). We experimentally confirm our GWAS results and demonstrate that RplD G70D and other macrolide binding site mutations are prevalent (present in 5.42% of 4850 isolates) and widespread (identified in 21/65 countries across two decades). Overall, our findings demonstrate the utility of conditional associations for improving the performance of microbial GWAS and advance our understanding of the genetic basis of macrolide resistance.
The Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project: defining a healthy volunteer cohort
Authors: Aguib Yasmine , Allouba Mona , Afify Alaa , Halawa Sarah , El-Khatib Mohamed , Sous Marina , Galal Aya , Abdelrahman Eslam , Shehata Nairouz , El Sawy Amr , Elmaghawry Mohamed , Anwer Shehab , Kamel Omnia , El Mozy Wesam , Khedr Hadir , Kharabish Ahmed , Thabet Nagwa , Theotokis Pantazis I. , Buchan Rachel , Govind Risha , Whiffin Nicola , Walsh Roddy , Aguib Heba , Elguindy Ahmed , O’Regan Declan P. , Cook Stuart A. , Barton Paul J. , Ware James S. , Yacoub Magdi
Published: October 2020

The integration of comprehensive genomic and phenotypic data from diverse ethnic populations offers unprecedented opportunities toward advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases are not representative of the global human population, making variant interpretation challenging, especially in underrepresented populations, such as the North African population. To address this, the Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project launched a study comprising 1000 individuals free of cardiovascular disease (CVD). Here, we present the first 391 Egyptian healthy volunteers recruited to establish a pilot phenotyped control cohort. All individuals underwent detailed clinical investigation, including cardiac magnetic resonance imaging (MRI), and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions. We identified 1262 variants in 27 cardiomyopathy genes of which 15.1% were not captured in current global and regional genetic reference databases (here: gnomAD and Great Middle Eastern Variome). The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in CVD and population genetics.
Best practices for the analytical validation of clinical whole-genome sequencing intended for the diagnosis of germline disease
Authors: Marshall Christian R. , Chowdhury Shimul , Taft Ryan J. , Lebo Mathew S. , Buchan Jillian G. , Harrison Steven M. , Rowsey Ross , Klee Eric W. , Liu Pengfei , Worthey Elizabeth A. , Jobanputra Vaidehi , Dimmock David , Kearney Hutton M. , Bick David , Kulkarni Shashikant , Taylor Stacie L. , Belmont John W. , Stavropoulos Dimitri J. , Lennon Niall J. ,   Medical Genome Initiative
Published: October 2020

Whole-genome sequencing (WGS) has shown promise in becoming a first-tier diagnostic test for patients with rare genetic disorders; however, standards addressing the definition and deployment practice of a best-in-class test are lacking. To address these gaps, the Medical Genome Initiative, a consortium of leading healthcare and research organizations in the US and Canada, was formed to expand access to high-quality clinical WGS by publishing best practices. Here, we present consensus recommendations on clinical WGS analytical validation for the diagnosis of individuals with suspected germline disease with a focus on test development, upfront considerations for test design, test validation practices, and metrics to monitor test performance. This work also provides insight into the current state of WGS testing at each member institution, including the utilization of reference and other standards across sites. Importantly, members of this initiative strongly believe that clinical WGS is an appropriate first-tier test for patients with rare genetic disorders, and at minimum is ready to replace chromosomal microarray analysis and whole-exome sequencing. The recommendations presented here should reduce the burden on laboratories introducing WGS into clinical practice, and support safe and effective WGS testing for diagnosis of germline disease.
CRY-dependent plasticity of tetrad presynaptic sites in the visual system of Drosophila at the morning peak of activity and sleep
Authors: Damulewicz Milena , Woźnicka Olga , Jasińska Małgorzata , Pyza Elżbieta
Published: October 2020

Tetrad synapses are formed between the retina photoreceptor terminals and postsynaptic cells in the first optic neuropil (lamina) of Drosophila. They are remodelled in the course of the day and show distinct functional changes during activity and sleep. These changes result from fast degradation of the presynaptic scaffolding protein Bruchpilot (BRP) by Cryptochrome (CRY) in the morning and depend on BRP-170, one of two BRP isoforms. This process also affects the number of synaptic vesicles, both clear and dense-core, delivered to the presynaptic elements. In cry01 mutants lacking CRY and in brpΔ170, the number of synaptic vesicles is lower in the morning peak of activity than during night-sleep while in wild-type flies the number of synaptic vesicles is similar at these two time points. CRY may also set phase of the circadian rhythm in plasticity of synapses. The process of synapse remodelling stimulates the formation of clear synaptic vesicles in the morning. They carry histamine, a neurotransmitter in tetrad synapses and seem to be formed from glial capitate projections inside the photoreceptor terminals. In turn dense-core vesicles probably carry synaptic proteins building the tetrad presynaptic element.
Reduced striatal vesicular monoamine transporter 2 in REM sleep behavior disorder: imaging prodromal parkinsonism
Authors: Beauchamp Leah C. , Villemagne Victor L. , Finkelstein David I. , Doré Vincent , Bush Ashley I. , Barnham Kevin J. , Rowe Christopher C.
Published: October 2020

Motor deficits in parkinsonism are caused by degeneration of dopaminergic nigral neurons. The success of disease-modifying therapies relies on early detection of the underlying pathological process, leading to early interventions in the disease phenotype. Healthy (n = 16), REM sleep behavior disorder (RBD) (n = 14), dementia with Lewy bodies (n = 10), and Parkinson’s disease (PD) (n = 20) participants underwent 18F-AV133 vesicular monoamine transporter type-2 (VMAT2) PET to determine the integrity of the nigrostriatal pathway. Clinical, neurophysiological and neuropsychological testing was conducted to assess parkinsonian symptoms. There was reduced VMAT2 levels in RBD participants in the caudate and putamen, indicating nigrostriatal degeneration. RBD patients also presented with hyposmia and anxiety, non-motor symptoms associated with parkinsonism. 18F-AV133 VMAT2 PET allows identification of underlying nigrostriatal degeneration in RBD patients. These findings align with observations of concurrent non-motor symptoms in PD and RBD participants of the Parkinson’s Progression Markers Initiative. Together, these findings suggest that RBD subjects have prodromal parkinsonism supporting the concept of conducting neuroprotective therapeutic trials in RBD-enriched cohorts. Ongoing longitudinal follow-up of these subjects will allow us to determine the time-window of clinical progression.