bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza-Associated Medical Visits Prevented by Influenza Vaccination in Young Children in Thailand, 2012–2014
Authors: Rolfes Melissa A , Olsen Sonja J , Kittikraisak Wanitchaya , Suntarattiwong Piyarat , Klungthong Chonticha , Ellison Damon , Mott Joshua A , Chotpitayasunondh Tawee
Published: June 2020

Despite recommendations, few children aged 6–35 months in Thailand receive seasonal influenza vaccination. Using previously estimated incidence and vaccine effectiveness data from the period 2012–2014, we estimate that up to 121 000 medical visits could be prevented each year with 50% coverage and expanded recommendations to children aged <5 years.
Insights into the control of metabolism and biomass accumulation in a staple C4 grass
Authors: Billakurthi Kumari , Schreier Tina B
Published: June 2020

This article comments on:

Chen J, Zhu M, Liu R, Zhang M, Lv Y, Liu Y, Xiao X, Yuan J, Cai H. 2020. BIOMASS YIELD 1 regulates Sorghum biomass and grain yield via the shikimate pathway. Journal of Experimental Botany 71, 5506–5520.
Is this an early stage merger? A case study on molecular gas and star formation properties of Arp 240
Authors: He Hao , Wilson C D , Sliwa Kazimierz , Iono Daisuke , Saito Toshiki
Published: June 2020

We present new high-resolution 12CO J = 1–0, J = 2–1, and 13CO J = 1–0 maps of the early stage merger Arp 240 (NGC 5257/8) obtained with the Atacama Large Millimeter/submillimeter Array (ALMA). Simulations in the literature suggest that the merger has just completed its first passage; however, we find that this system has a lower global gas fraction but a higher star formation efficiency (SFE) compared to typical close galaxy pairs, which suggests that this system may already be in an advanced merger stage. We combine the ALMA data with 12CO J = 3–2 observations from the Submillimeter Array and carry out RADEX modelling on several different regions. Both, the RADEX modelling and a local thermal equilibrium (LTE) analysis show that the regions are most likely to have a CO-to-H2 conversion factor αCO close to or perhaps even smaller than the typical value for (ultra)luminous infrared galaxies. Using 33-GHz data from the Very Large Array to measure the star formation rate, we find that most star-forming regions have molecular gas depletion times of less than 100 Myr. We calculated the SFE per free-fall time for different regions and find some regions appear to have values greater than 100 per cent. We find these regions generally show evidence for young massive clusters (YMCs). After exploring various factors, we argue that this is mainly due to the fact that radio continuum emission in those regions is dominated by that from YMCs, which results in an overestimate of the SFE per free-fall time.
Corruption, Opportunity Networks, and Gender
Authors: Wiesehomeier Nina , Verge Tània
Published: June 2020

Given the gender stereotype that women are more ethical than men, people should assess female politicians as being less corruptible. Yet information about access to networks suggests that opportunities to engage in unethical behavior may counter this perception. Using a conjoint analysis in a nationally representative survey in Spain, a country shaken by corruption scandals, we asked respondents to identify the more corruptible politician between two hypothetical local councilors by imagining an investor willing to offer a bribe to advance business interests. Results indicate that female politicians do symbolically stand for honesty. However, this assessment is offset by embeddedness cues signaling a woman politician’s access to opportunity networks. We discuss our findings in light of instrumentalist arguments for an increase of women in politics as a means to combat corruption.
Detecting Lineage-Specific Shifts in Diversification: A Proper Likelihood Approach
Authors: Laudanno Giovanni , Haegeman Bart , Rabosky Daniel L , Etienne Rampal S
Published: June 2020

The branching patterns of molecular phylogenies are generally assumed to contain information on rates of the underlying speciation and extinction processes. Simple birth–death models with constant, time-varying, or diversity-dependent rates have been invoked to explain these patterns. They have one assumption in common: all lineages have the same set of diversification rates at a given point in time. It seems likely, however, that there is variability in diversification rates across subclades in a phylogenetic tree. This has inspired the construction of models that allow multiple rate regimes across the phylogeny, with instantaneous shifts between these regimes. Several methods exist for calculating the likelihood of a phylogeny under a specified mapping of diversification regimes and for performing inference on the most likely diversification history that gave rise to a particular phylogenetic tree. Here, we show that the likelihood computation of these methods is not correct. We provide a new framework to compute the likelihood correctly and show, with simulations of a single shift, that the correct likelihood indeed leads to parameter estimates that are on average in much better agreement with the generating parameters than the incorrect likelihood. Moreover, we show that our corrected likelihood can be extended to multiple rate shifts in time-dependent and diversity-dependent models. We argue that identifying shifts in diversification rates is a nontrivial model selection exercise where one has to choose whether shifts in now-extinct lineages are taken into account or not. Hence, our framework also resolves the recent debate on such unobserved shifts. [Diversification; macroevolution; phylogeny; speciation]
To Be Seen, Heard, and Valued: Strategies to Promote a Sense of Belonging for Women and Underrepresented in Medicine Physicians
Authors: Haggins Adrianne N.
Published: June 2020

Lingering unconscious biases and daily cues continue to permeate and persist in academic medicine environments in the form of the exclusion of physicians who are women or racially/ethnically underrepresented in medicine. Academic medicine environments must change so that women and underrepresented in medicine racial/ethnic groups are seen, heard, and valued. A shared awareness among faculty, administrators, and trainees can inform the development of intentional strategies to alter individual behaviors, academic spaces, and institutional processes to cultivate a sense of belonging. Shifting the norms in medicine and the course of historical exclusion will require professional development in areas of inclusive teaching practices, skills to cultivate mentoring relationships with diverse trainees, and fostering discussions about the relevance of personal identity, as well as attention to the symbolism and imagery in institutional messages (e.g., portraits on the walls, website, marketing campaigns) and to the value of including community involvement in productivity metrics.
Globe-hopping
Authors: Chistikov Dmitry , Goulko Olga , Kent Adrian , Paterson Mike
Published: June 2020

We consider versions of the grasshopper problem (Goulko & Kent 2017
Proc. R. Soc. A
473
, 20170494) on the circle and the sphere, which are relevant to Bell inequalities. For a circle of circumference 2
π
, we show that for unconstrained lawns of any length and arbitrary jump lengths, the supremum of the probability for the grasshopper’s jump to stay on the lawn is one. For antipodal lawns, which by definition contain precisely one of each pair of opposite points and have length
π
, we show this is true except when the jump length
ϕ
is of the form
π
(
p
/
q
) with
p
,
q
coprime and
p
odd. For these jump lengths, we show the optimal probability is 1 − 1/
q
and construct optimal lawns. For a
pair
of antipodal lawns, we show that the optimal probability of jumping from one onto the other is 1 − 1/
q
for
p
,
q
coprime,
p
odd and
q
even, and one in all other cases. For an antipodal lawn on the sphere, it is known (Kent & Pitalúa-García 2014
Phys. Rev. A
90
, 062124) that if
ϕ
 = 
π
/
q
, where

q
∈

N

, then the optimal retention probability of 1 − 1/
q
for the grasshopper’s jump is provided by a hemispherical lawn. We show that in all other cases where 0 < 
ϕ
 < 
π
/2, hemispherical lawns are not optimal, disproving the hemispherical colouring maximality hypotheses (Kent & Pitalúa-García 2014
Phys. Rev. A
90
, 062124). We discuss the implications for Bell experiments and related cryptographic tests.
Ecology of the collapse of Rapa Nui society
Authors: Lima M. , Gayo E. M. , Latorre C. , Santoro C. M. , Estay S. A. , Cañellas-Boltà N. , Margalef O. , Giralt S. , Sáez A. , Pla-Rabes S. , Chr. Stenseth N.
Published: June 2020

Collapses of food producer societies are recurrent events in prehistory and have triggered a growing concern for identifying the underlying causes of convergences/divergences across cultures around the world. One of the most studied and used as a paradigmatic case is the population collapse of the Rapa Nui society. Here, we test different hypotheses about it by developing explicit population dynamic models that integrate feedbacks between climatic, demographic and ecological factors that underpinned the socio-cultural trajectory of these people. We evaluate our model outputs against a reconstruction of past population size based on archaeological radiocarbon dates from the island. The resulting estimated demographic declines of the Rapa Nui people are linked to the long-term effects of climate change on the island's carrying capacity and, in turn, on the ‘per-capita food supply’.
Contrasting the ecological effects of decreasing ice cover versus accelerated glacial melt on the High Arctic's largest lake
Authors: Michelutti Neal , Douglas Marianne S. V. , Antoniades Dermot , Lehnherr Igor , St. Louis Vincent L. , St. Pierre Kyra , Muir Derek C. G. , Brunskill Gregg , Smol John P.
Published: June 2020

Lake Hazen, the High Arctic's largest lake, has received an approximately 10-fold increase in glacial meltwater since its catchment glaciers shifted from net mass gain to net mass loss in 2007 common era (CE), concurrent with recent warming. Increased glacial meltwater can alter the ecological functioning of recipient aquatic ecosystems via changes to nutrient budgets, turbidity and thermal regimes. Here, we examine a rare set of five high-resolution sediment cores collected in Lake Hazen between 1990 and 2017 CE to investigate the influence of increased glacial meltwater versus alterations to lake ice phenology on ecological change. Subfossil diatom assemblages in all cores show two major shifts over the past approximately 200 years including: (i) a proliferation of pioneering, benthic taxa at approximately 1900 CE from previously depauperate populations; and (ii) a rise in planktonic taxa beginning at approximately 1980 CE to present-day dominance. The topmost intervals from each sequentially collected core provide exact dates and demonstrate that diatom regime shifts occurred decades prior to accelerated glacial inputs. These data show that diatom assemblages in Lake Hazen are responding primarily to intrinsic lake factors linked to decreasing duration of lake ice and snow cover rather than to limnological impacts associated with increased glacial runoff.
Muricauda hadalis sp. nov., a novel piezophile isolated from hadopelagic water of the Mariana Trench and reclassification of Muricauda antarctica as a later heterotypic synonym of Muricauda teanensis
Authors: Zhang Yan , Gao Yuxin , Pei Jiahao , Cao Junwei , Xie Zhe , Liu Rulong , Wang Li , Wei Yuli , Fang Jiasong
Published: June 2020

A novel marine Gram-stain-negative, non-motile, aerobic and rod-shaped bacterium, designated as strain MT-229T, was isolated from the deep seawater in the Mariana Trench and characterized phylogenetically and phenotypically. Bacterial optimal growth occurred at 30 °C (ranging 10–40 °C), pH 6 (ranging 3–11) and with 11 % (w/v) NaCl (ranging 0–17 %). Strain MT-229T was a piezophile, growing optimally at 20 MPa (range 0.1–70 MPa). The nearest phylogenetic neighbours were

Muricauda antarctica

CGMCC 1.2174T and

Muricauda taeanensis

JCM 17757T with 16S rRNA gene similarity of 98.7 %. The sole respiratory quinone was menaquinone-6 (MK-6). The major polar lipids were phosphatidylethanolamine (PE), two unidentified aminolipids (AL) and ten unidentified lipids. The major fatty acids of strain MT-229T were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The G+C content of the genomic DNA was 45.6 mol%. The combined genotypic and phenotypic data indicated that strain MT-229T represents a novel species of the genus

Muricauda

, for which the name Muricauda hadalis sp. nov. is proposed, with the type strain MT-229T (=DSM 109894T=MCCC 1K04201T). In addition, the whole-genome-based comparisons revealed that the type strains of

Muricauda antarctica

and Muricauda teanensis belong to a single species. It is, therefore, proposed that

M. antarctica

be recognized as a heterotypic synonym of M. teanensis.
Platon: identification and characterization of bacterial plasmid contigs in short-read draft assemblies exploiting protein sequence-based replicon distribution scores
Authors: Schwengers Oliver , Barth Patrick , Falgenhauer Linda , Hain Torsten , Chakraborty Trinad , Goesmann Alexander
Published: June 2020

Plasmids are extrachromosomal genetic elements that replicate independently of the chromosome and play a vital role in the environmental adaptation of bacteria. Due to potential mobilization or conjugation capabilities, plasmids are important genetic vehicles for antimicrobial resistance genes and virulence factors with huge and increasing clinical implications. They are therefore subject to large genomic studies within the scientific community worldwide. As a result of rapidly improving next-generation sequencing methods, the quantity of sequenced bacterial genomes is constantly increasing, in turn raising the need for specialized tools to (i) extract plasmid sequences from draft assemblies, (ii) derive their origin and distribution, and (iii) further investigate their genetic repertoire. Recently, several bioinformatic methods and tools have emerged to tackle this issue; however, a combination of high sensitivity and specificity in plasmid sequence identification is rarely achieved in a taxon-independent manner. In addition, many software tools are not appropriate for large high-throughput analyses or cannot be included in existing software pipelines due to their technical design or software implementation. In this study, we investigated differences in the replicon distributions of protein-coding genes on a large scale as a new approach to distinguish plasmid-borne from chromosome-borne contigs. We defined and computed statistical discrimination thresholds for a new metric: the replicon distribution score (RDS), which achieved an accuracy of 96.6 %. The final performance was further improved by the combination of the RDS metric with heuristics exploiting several plasmid-specific higher-level contig characterizations. We implemented this workflow in a new high-throughput taxon-independent bioinformatics software tool called Platon for the recruitment and characterization of plasmid-borne contigs from short-read draft assemblies. Compared to PlasFlow, Platon achieved a higher accuracy (97.5 %) and more balanced predictions (F1=82.6 %) tested on a broad range of bacterial taxa and better or equal performance against the targeted tools PlasmidFinder and PlaScope on sequenced

Escherichia coli

isolates. Platon is available at: http://platon.computational.bio/.
SARS-CoV-2 mutations altering regulatory properties: deciphering host’s and virus’s perspectives
Authors: Islam Abul Bashar Mir Md. Khademul , Khan Md. Abdullah-Al-Kamran
Published: June 2020

Since the first recorded case of the SARS-CoV-2, it has acquired several mutations in its genome while spreading throughout the globe. However, apart from some changes in protein coding, functional importance of these mutations in disease pathophysiology are still largely unknown. In this study, we investigated the significance of these mutations both from the host’s and virus’s perspective by analyzing the host miRNA binding and virus’s internal ribosome entry site (IRES), respectively. Strikingly, we observed that due to the acquired mutations, host miRNAs bind differently compared to the reference; where few of the miRNAs lost and few gained the binding affinity for targeting the viral genome. Moreover, functional enrichment analysis suggests that targets of both of these gained and lost miRNAs might be involved in various host immune signaling pathways. Also, we sought to shed some insights on the impacts of mutations on the IRES structure of SARS-CoV-2. Remarkably, we detected that three particular mutations in the IRES can disrupt its secondary structure which can further make the virus less functional. These results could be valuable in exploring the functional importance of the mutations of SARS-CoV-2 and could provide novel insights into the differences observed different parts of the world.
Loss of pH switch unique to SARS-CoV2 supports unfamiliar virus pathology
Authors: Paris Kristina A. , Santiago Ulises , Camacho Carlos J.
Published: June 2020

Cell surface receptor engagement is a critical aspect of viral infection. This paper compares the dynamics of virus-receptor interactions for SARS-CoV (CoV1) and CoV2. At low (endosomal) pH, the binding free energy landscape of CoV1 and CoV2 interactions with the angiotensin-converting enzyme 2 (ACE2) receptor is almost the same. However, at neutral pH the landscape is different due to the loss of a pH-switch (His445Lys) in the receptor binding domain (RBD) of CoV2 relative to CoV1. Namely, CoV1 stabilizes a transition state above the bound state. In situations where small external strains are applied by, say, shear flow in the respiratory system, the off rate of the viral particle is enhanced. As a result, CoV1 virions are expected to detach from cell surfaces in time scales that are much faster than the time needed for other receptors to reach out and stabilize virus attachment. On the other hand, the loss of this pH-switch, which sequence alignments show is unique to CoV2, eliminates the transition state and allows the virus to stay bound to the ACE2 receptor for time scales compatible with the recruitment of additional ACE2 receptors diffusing in the cell membrane. This has important implications for viral infection and its pathology. CoV1 does not trigger high infectivity in the nasal area because it either rapidly drifts down the respiratory tract or is exhaled. By contrast, this novel mutation in CoV2 should not only retain the infection in the nasal cavity until ACE2-rich cells are sufficiently depleted, but also require fewer particles for infection. This mechanism explains observed longer incubation times, extended period of viral shedding, and higher rate of transmission. These considerations governing viral entry suggest that number of ACE2-rich cells in human nasal mucosa, which should be significantly smaller for children (and females relative to males), should also correlate with onset of viral load that could be a determinant of higher virus susceptibility. Critical implications for the development of new vaccines to combat current and future pandemics that, like SARS-CoV2, export evolutionarily successful strains via higher transmission rates by viral retention in nasal epithelium are also discussed.
Evolution and spread of SARS-CoV-2 likely to be affected by climate
Authors: Bajaj Priyanka , Arya Prakash Chandra
Published: June 2020

COVID-19 pandemic has been extensively studied by many researchers. However, it is still unclear why it was restricted to higher latitudes during the initial days and later cascaded in the tropics. Here, we analyzed 176 SARS-CoV-2 genomes across different latitudes and climate (Koppen’s climate) that provided insights about within species virus evolution and its relation to abiotic factors. Two genetically variant groups, named as G1 and G2 were identified, well defined by four mutations. The G1 group (ancestor), is mainly restricted to warm and moist, temperate climate (Koppen’s C climate) while its descendent G2 group surpasses the climatic restrictions of G1, initially cascading into neighboring cold climate (D) of higher latitudes and later into hot climate of the tropics (A). It appears that the gradation of temperate climate (Cfa-Cfb) to cold climate (Dfa-Dfb) drives the evolution of G1 into G2 variant group which later adapted to tropical climate (A) as well. It seems this virus followed inverse latitudinal gradient in the beginning due to its preference towards temperate (C) and cold climate (D). Our work elucidates virus evolutionary studies combined with climatic studies can provide crucial information about the pathogenesis and natural spreading pathways in such outbreaks which is hard to achieve through individual studies. Mutational insights gained may help design an efficacious vaccine.

Graphical Abstract

In Brief

The authors elucidate adaptation of SARS-CoV-2 to different climates by studying phylogenetics and the distribution of strains on Koppen’s climate map.

Highlights

Phylogenetic network divides SARS-CoV-2 strains into two variant groups, G1 and G2.

G1 strains is restricted to Koppen’s“temperate”climate (mainlyCfa-Cfb).

G2 strains has evolved from G1 to sustain in other climates mainly “humid-continental” (Dfa-Dfb)and “tropical-savannah” (Aw)climate.
The Lifelines COVID-19 Cohort: a questionnaire-based study to investigate COVID-19 infection and its health and societal impacts in a Dutch population-based cohort
Authors: Intyre Kate Mc , Lanting Pauline , Deelen Patrick , Wiersma Henry , Vonk Judith M. , Ori Anil P.S. , Jankipersadsing Soesma A. , Warmerdam Robert , van Blokland Irene , Boulogne Floranne , Dijkema Marjolein X.L. , Herkert Johanna C. , Claringbould Annique , Bakker Olivier , Lopera Maya Esteban A. , Bültmann Ute , Zhernakova Alexandra , Reijneveld Sijmen A. , Zijlstra Elianne , Swertz Morris , Brouwer Sandra , van Ooijen R. , Angelini Viola , Dekker Louise , Sijtsma Anna , Scherjon Sicco A. , Dekens Jackie , Mierau Jochen O. , Boezen H. Marike , Franke Lude
Published: June 2020

The COVID-19 pandemic has affected billions of people around the world not only through the infection itself but also through its wider impact on public health and daily life. To assess the effects of the pandemic, a team of researchers across a wide range of disciplines developed and implemented the Lifelines COVID-19 questionnaire, leading to the development of the Lifelines COVID-19 cohort. This cohort is recruited from participants of the Lifelines prospective population cohort and the Lifelines NEXT birth cohort, and participants were asked to fill out detailed questionnaires about their physical and mental health and experiences on a weekly basis starting in late March of 2020 and on a bi-weekly basis staring in June 2020. The Lifelines region covers the three Northern provinces of the Netherlands— Drenthe, Groningen and Friesland—which together account for ∼10% of the Dutch population. To date, >70,000 people have responded to the questionnaires at least once, and the questionnaire program is still ongoing. Data collected by the questionnaires will be used to address four aspects of the outbreak: (1) how the COVID-19 pandemic developed in the three northern provinces of the Netherlands, (2) which environmental risk factors predict disease susceptibility and severity, (3) which genetic risk factors predict disease susceptibility and severity and (4) what are the psychological and societal impacts of the crisis.

Informed consent

All Lifelines and Lifelines NEXT participants have provided informed consent that provide the opportunity for add-on research.

Research involving human participants

Both the Lifelines and the Lifelines NEXT studies were approved by the ethics committee of the University Medical Center Groningen.
Breath-borne VOC Biomarkers for COVID-19
Authors: Chen Haoxuan , Qi Xiao , Ma Jianxin , Zhang Chunyang , Feng Huasong , Yao Maosheng
Published: June 2020

Rapid diagnosis of COVID-19 is key to controlling the pandemic. Here we report the potential breath-borne volatile organic compound (VOC) biomarkers for COVID-19. Higher levels of ethyl butanoate were detected in exhaled breath of COVID-19 patients (N=10) than healthy controls/health care workers (N=21), lung cancer (LC) patients (N=7) and backgrounds. In contrast, breath-borne butyraldehyde and isopropanol (an efficient SARS-CoV-2 inactivation agent) were significantly higher for non-COVID-19 respiratory infections (URTI) (N=22) than COVID-19, HC, LC patients and backgrounds. Breath-borne isopropanol emission from COVID-19 patients varied greatly up to ∼100-fold difference. COVID-19 patients had lower acetone levels than other subjects, except LC patients. The monitoring of ethyl butanoate, butyraldehyde and isopropanol could lend considerable support in rapidly screening COVID-19; and alerting the presence of COVID-19 patient in particular environments.

One Sentence Summary

COVID-19 patients emit distinctive VOC profiles
A chromosome-level genome assembly and annotation of the humpback grouperCromileptes altivelas
Authors: Sun Yun , Zhang Dongdong , Shi Jianzhi , Chen Guisen , Wu Ying , Shen Yang , Cao Zhenjie , Zhang Linlin , Zhou Yongcan
Published: June 2020

Cromileptes altivelasthat belongs to Serranidae in the order Perciformes, is widely distributed throughout the tropical waters of the Indo-West Pacific regions. Due to their excellent food quality and abundant nutrients, it has become a popular marine food fish with high market values. Here, we reported a chromosome-level genome assembly and annotation of the humpback grouper genome using more than 103X PacBio long-reads and high-throughput chromosome conformation capture (Hi-C) technologies. The N50 contig length of the assembly is as large as 4.14 Mbp, the final assembly is 1.07 Gb with N50 of scaffold 44.78 Mb, and 99.24% of the scaffold sequences were anchored into 24 chromosomes. The high-quality genome assembly also showed high gene completeness with 27,067 protein coding genes and 3,710 ncRNAs. This high accurate genome assembly and annotation will not only provide an essential genome resource forC. altivelasbreeding and restocking, but will also serve as a key resource for studying fish genomics and genetics.
The Effect of Uncertainty on Prediction Error in the Action-Perception Loop
Authors: Perrykkad Kelsey , Lawson Rebecca P. , Jamadar Sharna , Hohwy Jakob
Published: June 2020

Among all their sensations, agents need to distinguish between those caused by themselves and those caused by external causes. The ability to infer agency is particularly challenging under conditions of uncertainty. Within the predictive processing framework, this should happen through active control of prediction error that closes the action-perception loop. Here we use a novel, temporally-sensitive, behavioural proxy for prediction error to show that it is minimised most quickly when variability is low, but also when volatility is high. Further, when human participants report agency, they show steeper prediction error minimisation. We demonstrate broad effects of uncertainty on accuracy of agency judgements, movement, policy selection, and hypothesis switching. Measuring autism traits, we find differences in policy selection, sensitivity to uncertainty and hypothesis switching despite no difference in overall accuracy.
Disentangling the biological information encoded in disordered mitochondrial morphology through its rapid elicitation by iCMM
Authors: Miyamoto Takafumi , Uosaki Hideki , Mizunoe Yuhei , Goto Satoi , Yamanaka Daisuke , Masuda Masato , Yoneyama Yosuke , Nakamura Hideki , Hattori Naoko , Takeuchi Yoshinori , Sekiya Motohiro , Matsuzaka Takashi , Hakuno Fumihiko , Takahashi Shin-Ichiro , Yahagi Naoya , Ito Koichi , Shimano Hitoshi
Published: June 2020

Mitochondrial morphology is dynamically changed in conjunction with spatiotemporal functionality. Although considerable efforts have been made to understand why abnormal mitochondrial morphology occurs in various diseases, the biological significance of mitochondrial morphology in states of health and disease remains to be elucidated owing to technical limitations. In the present study, we developed a novel method, termed inducible Counter Mitochondrial Morphology (iCMM), to purposely manipulate mitochondrial morphological patterns on a minutes timescale, using a chemically inducible dimerization system. Using iCMM, we showed that mitochondrial morphological changes rapidly lead to the characteristic reconstitution of various biological information, which is difficult to investigate by conventional genetic engineering. The manipulation of mitochondrial morphology using iCMM can improve our understanding of the interplay between mitochondrial morphology and cellular functions.
Development of optogenetic tools to manipulate cell cycle checkpoints
Authors: Goto Yuhei , Aoki Kazuhiro
Published: June 2020

In order to understand the systematic regulation of the cell cycle, we need more precise tools for cell-cycle perturbation. Optogenetics is a powerful technique for precisely controlling cellular signaling at higher spatial and temporal resolution. Here, we report optogenetic tools for the rapid and reversible control of cell-cycle checkpoints with a red/far-red light photoreceptor, phytochrome B (PhyB). We established fission yeast cells producing phycocyanobilin as a chromophore of PhyB, and demonstrated light-dependent protein recruitment to the plasma membrane, nucleus, and kinetochore. Using this system, we developed optogenetic manipulation of the cell cycle in two ways: the Opto-G2/M checkpoint triggered G2/M cell cycle arrest in response to red light, and Opto-SAC induced a spindle assembly checkpoint (SAC) in response to red light and then quickly released the SAC by far-red light.
Genetic susceptibility to pneumonia: A GWAS meta-analysis between UK Biobank and FinnGen
Authors: Campos Adrian I. , Kho Pik Fang , Vazquez-Prada Karla X. , García-Marín Luis M. , Martin Nicholas G. , Cuéllar-Partida Gabriel , Rentería Miguel E.
Published: June 2020

Rationale

Pneumonia is a respiratory condition with complex aetiology. Host genetic variation is thought to contribute to individual differences in susceptibility and symptom manifestation.

Methods

We analysed pneumonia data from the UK Biobank (14,780 cases and 439,096 controls) and FinnGen (9,980 cases and 86,519 controls). We perform genome-wide association study (GWAS) meta-analysis, gene-based test, colocalisation, genetic correlation, latent causal variable and polygenic prediction in an independent Australian sample (N=5,595) to draw insights into the genetic aetiology of pneumonia risk.

Results

We identify two independent loci on chromosome 15 (lead SNPs rs2009746 and rs76474922) to be associated with pneumonia(p<5e-8). Gene-based tests revealed eighteen genes in chromosomes 15,16 and 9, includingIL127, PBX3, APOBRand smoking related genesCHRNA3/5, associated with pneumonia. Evidence ofHYKKandPBX3involvement in pneumonia risk was supported by eQTL colocalisation analysis. We observed genetic correlations between pneumonia and cardiorespiratory, psychiatric and inflammatory related traits. Latent causal variable analysis suggests a strong genetic causal relationship cardiovascular health phenotypes and pneumonia risk. Polygenic risk scores (PRS) for pneumonia significantly predicted self-reported pneumonia history in an independent Australian sample, albeit with a small effect size (OR=1.11 95%CI=[1.04-1.19], p<0.05). Sensitivity analyses suggested the associations in chromosome 15 are mediated by smoking history, but the association of genes in chromosome 16 and 9, and polygenic prediction were robust to adjustment for smoking.

Conclusions

Altogether, our results highlight common genetic variants, genes and potential pathways that contribute to individual differences in susceptibility to pneumonia, and advance our understanding of the genetic factors underlying heterogeneity in respiratory medical outcomes.
An urgent need for a paradigm shift in HIV testing for older children: A sine qua non condition to achieve an AIDS-free generation
Authors: Yumo H.A. , Ndenkeh J.J.N. , Sieleunou I. , Nsame D.N. , Kuwoh P.B. , Beissner M. , Kuaban C.
Published: June 2020

Background

Achieving an AIDS-free generation requires effective pediatric testing and treatment services. While pediatric HIV testing has been more focused on children below 18 months through PMTCT, the yield of this approach remains unclear comparatively to testing children above 18 months through routine PITC. This study aimed at bridging this evidence gap and provide knowledge to guide pediatric HIV testing investments.

Materials and Methods

Parents visiting or receiving HIV care in three hospitals in Cameroon were invited to test their children for HIV. HIV testing was done using PCR and antibody rapid tests for children < 18 months and those ≥18 months, respectively. We compared HIV case detection and ART initiation between the two subgroups of children and this using Chi-square test at 5% significant level.

Results

A total of 4079 children aged 6 weeks-15 years were included in the analysis. Compared to children < 18 months, children group ≥18 months was 4-fold higher among those who enrolled in the study (80.3% vs 19.7%, p<0.001); 3.5-fold higher among those who tested for HIV (77.6% vs 22.4%, p<0.001); 6-fold higher among those who tested HIV+ (85.7% vs 14.3%, p=0.241) and 11-fold higher among those who enrolled on ART (91.7% vs 8.3%, p< 0.028).

Conclusions

Our results show that 4 out of 5 children who tested HIV+ and over 90% of ART enrolled cases were children ≥ 18 months. Thus, while rolling out PCR HIV testing technology for neonates and infants, committing adequate and proportionate resources in antibody rapid testing for older children is a sine quo none condition to achieve an AIDS-free generation.
Qualitative forecast and temporal evolution of the disease spreading using a simplified model and COVID-19 data for Italy
Authors: Simeone Roberto
Published: June 2020

In a previous paper [1] a simplified SEIR model applied to COVID-19 cases detected in Italy, including the lockdown period, has shown a good fitting to the time evolution of the disease during the observed period.

In this paper that model is applied to the initial data available for Italy in order to forecast, in a qualitative way, the time evolution of the disease spreading. The values obtained are to be considered indicative.

The same model has been applied both to the data relating to Italy and to some italian regions generally finding good qualitative results.

The only tuning parameter in the model is the ‘incubation period’ τ.

In this modelization the tuning parameter, together with the calculated growth rate of the exponential curve used to approximate the early stage data, are in strong relationship with the compartments’ transfer rates.

The relationships between the parameters simplify modeling by allowing a rough (not supported by statistical considerations) forecast of the time evolution, starting from the first period of growth of the diffusion.

Conclusions

A simplified compartmental model that uses only the incubation period and the exponential growth rate as parameters is applied to the COVID-19 data for Italy in several periods of the initial growth of the diffusion showing the different stages of the spread evolution. The simplification is based on the strong protection measures that were in place in Italy during the lockdown period after the initial free diffusion.
Cost-effectiveness and return on investment of protecting health workers in low- and middle-income countries during the COVID-19 pandemic
Authors: Risko Nicholas , Werner Kalin , Offorjebe O. Agatha , Vecino-Ortiz Andres I. , Wallis Lee A. , Razzak Junaid
Published: June 2020

Background

In this paper, we predict the health and economic consequences of immediate investment in personal protective equipment (PPE) for health care workers (HCWs) in low- and middle-income countries (LMICs).

Methods

To account for health consequences, we estimated mortality for health care workers (HCW), and present a cost-effectiveness and return on investment (ROI) analysis using a decision-analytic model with Bayesian multivariate sensitivity analysis and Monte Carlo simulation. Inputs were used from the World Health Organization Essential Supplies Forecasting Tool and the Imperial College of London epidemiologic model.

Results

An investment of $9.6 billion USD would adequately protect HCWs in all LMICs. This intervention saves 2,299,543 lives across LMICs, costing $59 USD per HCW case averted and $4,309 USD per HCW life saved. The societal ROI is $755.3 billion USD, the equivalent of a 7,932% return. Regional and national estimates are also presented. In scenarios where PPE remains scarce, 70-100% of HCWs will get infected, irrespective of nationwide social distancing policies. Maintaining HCW infection rates below 10% and mortality below 1% requires inclusion of a PPE scale-up strategy as part of the pandemic response.

Discussion

In conclusion, wide-scale procurement and distribution of PPE for LMICs is an essential strategy to prevent widespread HCW morbidity and mortality. It is cost-effective and yields a large downstream return on investment.
An agent based modelling approach to study lockdown efficacy for infectious disease spreads
Authors: Pathak Anagh , Mohan Varun Madan , Banerjee Arpan
Published: June 2020

We sought to simulate lockdown scenarios using an Agent Based Modelling (ABM) strategy, which is a new modelling paradigm that seeks to simulate the actions and interactions of autonomous agents within an environment. The spread of infectious viral diseases occur over a connected social network. Specifically, the goal was to understand the effect of network topology and lockdown strategies on disease spreading dynamics. To explore the effect of topology we assumed the social network over which the disease spreads to have small-world or scale-free properties characterized by a rewiring probability and degree distribution respectively. Lockdowns were simulated as intervention strategies that modified the spreading dynamics of infection over a given graph structure through changes in properties of agent interaction. Lockdown efficacy was assessed by the maximum number of infections recorded during a simulation run. Thereafter, lockdown efficacy was evaluated as a function of lockdown start times and duration. Thus, we propose that ABM approach can be used to assess various lockdown strategies that aim to prevent breakdown of medical infrastructure while accounting for realistic social network configurations specific to a local population.

Notation
Decoding the microstructural properties of white matter using realistic models
Authors: Hédouin Renaud , Metere Riccardo , Chan Kwok-Shing , Licht Christian , Mollink Jeroen , van Walsum Anne-Marievan Cappellen , Marques José P.
Published: June 2020

Multi-echo gradient echo (ME-GRE) magnetic resonance signal evolution in white matter has a strong dependence on the orientation of myelinated axons with respect to the main static field. Although analytical solutions have been able to predict some of the white matter (WM) signal behaviour of the hollow cylinder model, it has been shown that realistic models of WM offer a better description of the signal behaviour observed.

In this work, we present a pipeline to (i) generate realistic 2D WM models with their microstructure based on real axon morphology with adjustable fiber volume fraction (FVF) and g-ratio. We (ii) simulate their interaction with the static magnetic field to be able to simulate their MR signal. For the first time, we (iii) demonstrate that realistic 2D WM models can be used to simulate a MR signal that provides a good approximation of the signal obtained from a real 3D WM model derived from electron microscopy. We then (iv) demonstratein silicothat 2D WM models can be used to predict microstructural parameters in a robust way if ME-GRE multi-orientation data is available and the main fiber orientation in each pixel is known using DTI. A deep learning network was trained and characterized in its ability to recover the desired microstructural parameters such as FVF, g-ratio, free and bound water transverse relaxation and magnetic susceptibility. Finally, the network was trained to recover these micro-structural parameters from anex vivodataset acquired in 9 orientations with respect to the magnetic field and 12 echo times. We demonstrate that this is an overdetermined problem and that as few as 3 orientations can already provide comparable results for some of the decoded metrics.

[Highlights] - A pipeline to generate realistic white models of arbitrary fiber volume fraction and g-ratio is presented; - We present a methodology to simulated the gradient echo signal from segmented 2D and 3D models of white matter, which takes into account the interaction of the static magnetic field with the anisotropic susceptibility of the myelin phospholipids; - Deep Learning Networks can be used to decode microstructural white matter parameters from the signal of multi-echo multi-orientation data;
Interspecific introgression and natural selection in the evolution of Japanese apricot (Prunus mume)
Authors: Numaguchi Koji , Akagi Takashi , Kitamura Yuto , Ishikawa Ryo , Ishii Takashige
Published: June 2020

Domestication and population differentiation in crops involve considerable phenotypic changes. The logs of these evolutionary paths, including natural/artificial selection, can be found in the genomes of the current populations. However, these profiles have been little studied in tree crops, which have specific characters, such as long generation time and clonal propagation, maintaining high levels of heterozygosity.

We conducted exon-targeted resequencing of 129 genomes in the genusPrunus, mainly Japanese apricot (Prunus mume), and apricot (P. armeniaca), plum (P. salicina), and peach (P. persica). Based on their genome-wide single nucleotide polymorphisms merged with published resequencing data of 79 ChineseP. mumecultivars, we inferred complete and ongoing population differentiation inP. mume.

Sliding window characterization of the indexes for genetic differentiation identified interspecific fragment introgressions betweenP. mumeand related species (plum and apricot). These regions often exhibited strong selective sweeps formed in the paths of establishment or formation of substructures ofP. mume, suggesting thatP. mumehas frequently imported advantageous genes from other species in the subgenusPrunusas adaptive evolution.

These findings shed light on the complicated nature of adaptive evolution in a tree crop that has undergone interspecific exchange of genome fragments with natural/artificial selection.
Expression ofAce2, Tmprss2, andFurinin mouse ear tissue
Authors: Uranaka Tsukasa , Kashio Akinori , Ueha Rumi , Sato Taku , Bing Han , Ying Gao , Kinoshita Makoto , Kondo Kenji , Yamasoba Tatsuya
Published: June 2020

Objectives

Intracellular entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on the interaction between its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2) and depends on Furin-mediated spike 23 protein cleavage and spike protein priming by host cell proteases including 24 transmembrane protease serine 2 (TMPRSS2).Tmprss1, Tmprss3,andTmprss5are expressed in the spiral ganglion neurons and the organ of Corti in the inner ear; however,Ace2, Tmprss2,andFurinexpression profiles in the middle ear remain unclear. Therefore, this study aimed to analyzeAce2, Tmprss2,andFurinexpression in the middle and inner ear of mice.

Study Design

Animal research.

Setting

Department of Otolaryngology and Head and Neck Surgery, University of Tokyo.

Methods

We performed immunohistochemical analysis to examine the distribution of Ace2, Tmprss2, and Furin in the eustachian tube, middle ear space, and cochlea of mice.

Results

Ace2 was expressed in the cytoplasm in the middle ear epithelium, eustachian tube epithelium, stria vascularis, and spiral ganglion. Tmprss2 and Furin were widely expressed in the middle ear spaces and the cochlea.

Conclusion

Co-expression of Ace2, Tmprss2, and Furin in the middle ear indicates that the middle ear is susceptible to SARS-CoV-2 infections, thus warranting the use of personal protective equipment during mastoidectomy for coronavirus disease (COVID-19) patients.
Spinal Column Architecture of the Flexible SPP1 Bacteriophage Tail Tube
Authors: Zinke Maximilian , Sachowsky Katrin A. A. , Öster Carl , Zinn-Justin Sophie , Ravelli Raimond B.G. , Schröder Gunnar F. , Habeck Michael , Lange Adam
Published: June 2020

Phage therapy has recently regained attention at combating multidrug-resistant bacteria. In 2019, tailed bacteriophages of theSiphoviridaefamily were engineered to successfully treat a disseminated bacterial infection after all other drugs had failed.(1) This family of phages features a long, flexible, non-contractile tail that has been difficult to characterize structurally. Here, we present the atomic structure of the tail-tube of the bacteriophage SPP1 – a member of this family. Our hybrid structure is based on the integration of structural restraints from solid-state NMR and a density map from cryo-EM. We show that the tail tube protein (TTP) gp17.1 organizes into hexameric rings that are stacked by flexible linker domains and, thus, form a hollow flexible tube with a negatively charged lumen suitable for the transport of DNA.

One sentence summary

Integrative structural biology by solid-state NMR and cryo-EM enables structure determination of the flexible tail of the bacteriophage SPP1.
DGAT1 is a lipid metabolism oncoprotein that enables cancer cells to accumulate fatty acid while avoiding lipotoxicity
Authors: Wilcock Daniel J. , Badrock Andrew P. , Owen Rhys , Guerin Melissa , Southam Andrew D. , Johnston Hannah , Ogden Samuel , Fullwood Paul , Watson Joanne , Ferguson Harriet , Ferguson Jennifer , Richardson Daniel A. , Lloyd Gavin R. , Jankevics Andris , Dunn Warwick B. , Wellbrock Claudia , Lorigan Paul , Ceol Craig , Francavilla Chiara , Smith Michael P. , Hurlstone Adam F. L.
Published: June 2020

Dysregulated cellular metabolism is a hallmark of cancer. As yet, few druggable oncoproteins directly responsible for this hallmark have been identified. Increased fatty acid acquisition allows cancer cells to meet their membrane biogenesis, ATP, and signaling needs. Excess fatty acids suppress growth factor signaling and cause oxidative stress in non-transformed cells, but surprisingly not in cancer cells. Molecules underlying this cancer adaptation may provide new drug targets. Here, we identify Diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, as a frequently up-regulated oncoprotein allowing cancer cells to tolerate excess fatty acids. DGAT1 over-expression alone induced melanoma in zebrafish melanocytes, and co-operated with oncogenic BRAF or NRAS for more rapid melanoma formation. Mechanistically, DGAT1 stimulated melanoma cell growth through sustaining mTOR kinase–S6 kinase signaling and suppressed cell death by tempering fatty acid oxidation, thereby preventing accumulation of reactive oxygen species including lipid peroxides.

SIGNIFICANCE

We show that DGAT1 is abona fideoncoprotein capable of inducing melanoma formation and co-operating with other known drivers of melanoma. DGAT1 facilitates enhanced fatty acid acquisition by melanoma cells through suppressing lipototoxicity. DGAT1 is also critical for maintaining S6K activity required for melanoma cell growth.