bluuebunny/crossref_metadata_2025 huggingface dataset:
Global genetic diversity patterns and transmissions of SARS-CoV-2
Authors: Chen Zhi-wei , Li Zhao , Li Hu , Ren Hong , Hu Peng
Published: May 2020

Background

Since it was firstly discovered in China, the SARS-CoV-2 epidemic has caused a substantial health emergency and economic stress in the world. However, the global genetic diversity and transmissions are still unclear.

Methods

3050 SARS-CoV-2 genome sequences were retrieved from GIASID database. After aligned by MAFFT, the mutation patterns were identified by phylogenetic tree analysis.

Results

We detected 17 high frequency (>6%) mutations in the 3050 sequences. Based on these mutations, we classed the SARS-CoV-2 into four main groups and 10 subgroups. We found that group A was mainly presented in Asia, group B was primarily detected in North America, group C was prevailingly appeared in Asia and Oceania and group D was principally emerged in Europe and Africa. Additionally, the distribution of these groups was different in age, but was similar in gender. Group A, group B1 and group C2 were declined over time, inversely, group B2, group C3 and group D were rising. At last, we found two apparent expansion stages (late Jan-2020 and late Feb-2020 to early Mar-2020, respectively). Notably, most of groups are quickly expanding, especially group D.

Conclusions

We classed the SARS-CoV-2 into four main groups and 10 subgroups based on different mutation patterns at first time. The distribution of the 10 subgroups was different in geography, time and age, but not in gender. Most of groups are rapidly expanding, especially group D. Therefore, we should attach importance to these genetic diversity patterns of SARS-CoV-2 and take more targeted measures to constrain its spread.
The First Wave of COVID-19 in Israel – Initial Analysis of Publicly Available Data
Authors: Last Mark
Published: May 2020

The first case of COVID-19 was confirmed in Israel on February 21, 2020. Within approximately 30 days, the total number of confirmed cases climbed up to 1,000, accompanied by a doubling period of less than 3 days. About one week later, after this number exceeded 4, 000 cases, and following some extreme lockdown measures taken by the Israeli government, the daily infection rate started a sharp decrease from the peak value of 1,131 down to slightly more than 100 new confirmed cases on April 30. Motivated by this encouraging data, similar to the trends observed in many other countries, along with the growing economic pressures, the Israeli government has quickly lifted most of its emergency regulations. Throughout May, the daily number of new cases stayed at a very low level of 20 – 40 until at the end of May it started a steady increase, exceeding 1, 000 by the end of June and 2,000 on July 22. As suggested by some experts and popular media, this disturbing trend may be even a part of a “second wave”. This article attempts to analyze the currently available data on Israel, compared to three European countries (Greece, Italy, and Sweden), in order to understand the local dynamics of COVID-19, assess the effect of the implemented intervention measures, and discuss some plausible scenarios for the foreseeable future.
Suboptimal biological sampling as a probable cause of false-negative COVID-19 diagnostic test results
Authors: Kinloch Natalie N. , Ritchie Gordon , Brumme Chanson J. , Dong Winnie , Dong Weiyan , Lawson Tanya , Jones R. Brad , Montaner Julio S.G. , Leung Victor , Romney Marc G. , Stefanovic Aleksandra , Matic Nancy , Lowe Christopher F. , Brumme Zabrina L.
Published: May 2020

Improper nasopharyngeal swab collection could contribute to false-negative COVID-19 results. In support of this, specimens from confirmed or suspected COVID-19 cases that tested negative or indeterminate (i.e. suspected false-negatives) contained less human DNA (a stable molecular marker of sampling quality) compared to a representative pool of specimens submitted for testing.
COVID-19 Infection in Children: Estimating Pediatric Morbidity and Mortality
Authors: Barton Michelle , Mehta Kayur , Kumar Kriti , Lu Jielin , Le Saux Nicole , Sampson Margaret , Robinson Joan
Published: May 2020

BACKGROUND

Estimates of pediatric morbidity and mortality from COVID-19 are vital for planning optimal use of human and material resources throughout this pandemic.

METHODS

Government websites from countries with minimum 1000 cases in adults and children on April 13, 2020 were searched to find the number of cases confirmed in children, the age range, and the number leading to hospitalization, intensive care unit (ICU) admission or death. A systematic literature search was performed April 13, 2020 to find additional data from cases series.

RESULTS

Data on pediatric cases were available from government websites for 23 of the 70 countries with minimum 1000 cases by April 13, 2020. Of 424 978 cases in these 23 countries, 8113 (1.9%) occurred in children. Nine publications provided data from 4251 cases in 4 additional countries. Combining data from the websites and the publications, 330 of 2361 cases required admission (14%). The ICU admission rate was 2.2 % of confirmed cases (44 of 2031) and 7.2% of admitted children (23 of 318). Death was reported for 15 cases.

CONCLUSION

Children accounted for 1.9% of confirmed cases. The true incidence of pediatric infection and disease will only be known once testing is expanded to individuals with less severe or no symptoms. Admission rates vary from 0.3 to 10% of confirmed cases (presumably varying with the threshold for testing) with about 7% of admitted children requiring ICU care. Death is rare in middle and high income countries.
Cancer phylogenetic tree inference at scale from 1000s of single cell genomes
Authors: Salehi Sohrab , Dorri Fatemeh , Chern Kevin , Kabeer Farhia , Rusk Nicole , Funnell Tyler , Williams Marc J , Lai Daniel , Andronescu Mirela , Campbell Kieran R. , McPherson Andrew , Aparicio Samuel , Roth Andrew , Shah Sohrab , Bouchard-Côté Alexandre
Published: May 2020

A new generation of scalable single cell whole genome sequencing (scWGS) methods allows unprecedented high resolution measurement of the evolutionary dynamics of cancer cell populations. Phylogenetic reconstruction is central to identifying sub-populations and distinguishing the mutational processes that gave rise to them. Existing phylogenetic tree building models do not scale to the tens of thousands of high resolution genomes achievable with current scWGS methods. We constructed a phylogenetic model and associated Bayesian inference procedure, sitka, specifically for scWGS data. The method is based on a novel phylogenetic encoding of copy number (CN) data, the sitka transformation, that simplifies the site dependencies induced by rearrangements while still forming a sound foundation to phylogenetic inference. The sitka transformation allows us to design novel scalable Markov chain Monte Carlo (MCMC) algorithms. Moreover, we introduce a novel point mutation calling method that incorporates the CN data and the underlying phylogenetic tree to overcome the low per-cell coverage of scWGS. We demonstrate our method on three single cell datasets, including a novel PDX series, and analyse the topological properties of the inferred trees. Sitka is freely available athttps://github.com/UBC-Stat-ML/sitkatree.git.
Mutations inMYLPFcause a novel segmental amyoplasia that manifests as distal arthrogryposis
Authors: Chong Jessica X. , Talbot Jared C. , Teets Emily M. , Previs Samantha , Martin Brit L. , Shively Kathryn M. , Marvin Colby T. , Aylsworth Arthur S. , Saadeh-Haddad Reem , Schatz Ulrich A. , Inzana Francesca , Ben-Omran Tawfeg , Almusafri Fatima , Al-Mulla Mariam , Buckingham Kati J. , Harel Tamar , Mor-Shaked Hagar , Radhakrishnan Periyasamy , Girisha Katta M , Nayak Shalini S. , Shukla Anju , Dieterich Klaus , Faure Julien , Rendu John , Capri Yline , Latypova Xenia , Nickerson Deborah A. , Warshaw David , Janssen Paul M. ,   University of Washington Center for Mendelian Genomics, Amacher Sharon L. , Bamshad Michael J.
Published: May 2020

We identified ten persons in six consanguineous families with Distal Arthrogryposis (DA) who had congenital contractures, scoliosis, and short stature. Exome sequencing revealed that each affected person was homozygous for one of two different rare variants (c.470G>T, p.(Cys157Phe) or c.469T>C, p.(Cys157Arg)) affecting the same residue ofmyosin light chain, phosphorylatable, fast skeletal muscle(MYLPF). In a seventh family, a c.487G>A, p.(Gly163Ser) variant inMYLPFarosede novoin a father, who transmitted it to his son. In an eighth family comprised of seven individuals with dominantly-inherited DA, a c.98C>T, p.(Ala33Val) variant segregated in all four persons tested. Variants inMYLPFunderlie both dominant and recessively inherited DA. Mylpf protein models suggest that the residues associated with dominant DA interact with myosin whereas the residues altered in families with recessive DA only indirectly impair this interaction. Pathological and histological exam of a foot amputated from an affected child revealed complete absence of skeletal muscle (i.e., segmental amyoplasia). To investigate the mechanism for this finding, we generated an animal model for partial MYLPF impairment by knocking out zebrafishmylpfa. Themylpfamutant had reduced trunk contractile force and complete pectoral fin paralysis, demonstrating thatmylpfimpairment most severely affects limb movement.mylpfamutant muscle weakness was most pronounced in an appendicular muscle and was explained by reduced myosin activity and fiber degeneration. Collectively, our findings demonstrate that partial loss of MYLPF function can lead to congenital contractures, likely as a result of degeneration of skeletal muscle in the distal limb.
Microglial phagocytosis dysfunction is related to local neuronal activity in a genetic model of epilepsy
Authors: Sierra-Torre Virginia , Plaza-Zabala Ainhoa , Bonifazi Paolo , Abiega Oihane , Díaz-Aparicio Irune , Tegelberg Saara , Lehesjoki Anna-Elina , Valero Jorge , Sierra Amanda
Published: May 2020

Microglial phagocytosis of apoptotic cells is an essential component of the brain regenerative response in neurodegenerative diseases. Phagocytosis is very efficient in physiological conditions, as well as during apoptotic challenge induced by excitotoxicity or inflammation, but is impaired in mouse and human mesial temporal lobe epilepsy (MTLE). Here we extend our studies to a genetic model of progressive myoclonus epilepsy type 1 (EPM1) in mice lacking cystatin B (CSTB), an inhibitor of cysteine proteases involved in lysosomal proteolysis. We first demonstrated that microglial phagocytosis was impaired in the hippocampus inCstbknock-out (KO) mice when seizures arise and hippocampal atrophy begins, at 1 month of age. To test if this blockage was related to the lack ofCstbin microglia, we used anin vitromodel of phagocytosis and siRNAs to acutely reduceCstbexpression but we found no significant effect in the phagocytosis of apoptotic cells. We then tested whether seizures were involved in the phagocytosis impairment, similar to MTLE, and analyzedCstbKO mice before seizures begin, at postnatal day 14. Here, phagocytosis impairment was restricted to the granule neuron layer but not to the subgranular zone, where there are no active neurons. Furthermore, we observed apoptotic cells (both phagocytosed and not phagocytosed) inCstbdeficient mice at close proximity to active, cFos+neurons and used mathematical modeling to demonstrate that the physical relationship between apoptotic cells and cFos+ neurons was specific forCstbKO mice. These results suggest a complex crosstalk between apoptosis, phagocytosis and neuronal activity, hinting that local neuronal activity could be related to phagocytosis dysfunction inCstbKO mice. Overall, this data suggest that phagocytosis impairment is an early feature of hippocampal damage in epilepsy and opens novel therapeutic approaches for epileptic patients based on targeting microglial phagocytosis.
Full-length 16S rRNA gene amplicon analysis of human gut microbiota using MinION™ nanopore sequencing confers species-level resolution
Authors: Matsuo Yoshiyuki , Komiya Shinnosuke , Yasumizu Yoshiaki , Yasuoka Yuki , Mizushima Katsura , Takagi Tomohisa , Kryukov Kirill , Fukuda Aisaku , Morimoto Yoshiharu , Naito Yuji , Okada Hidetaka , Bono Hidemasa , Nakagawa So , Hirota Kiichi
Published: May 2020

Background

Species-level genetic characterization of complex bacterial communities has important clinical applications in both diagnosis and treatment. Amplicon sequencing of the 16S ribosomal RNA (rRNA) gene has proven to be a powerful strategy for the taxonomic classification of bacteria. This study aims to improve the method for full-length 16S rRNA gene analysis using the nanopore long-read sequencer MinION™. We compared it to the conventional short-read sequencing method in both a mock bacterial community and human fecal samples.

Results

We modified our existing protocol for full-length 16S amplicon sequencing by MinION™. A new strategy for library construction with an optimized primer set overcame PCR-associated bias and enabled taxonomic classification across a broad range of bacterial species. We compared the performance of full-length and short-read 16S amplicon sequencing for the characterization of human gut microbiota with a complex bacterial composition. The relative abundance of dominant bacterial genera was highly similar between full-length and short-read sequencing. At the species level, MinION™ long-read sequencing had better resolution for discriminating between members of particular taxa such asBifidobacterium, allowing an accurate representation of the sample bacterial composition.

Conclusions

Our present microbiome study, comparing the discriminatory power of full-length and short-read sequencing, clearly illustrated the analytical advantage of sequencing the full-length 16S rRNA gene, which provided the requisite species-level resolution and accuracy in clinical settings.
Is diversity in worker body size important for the performance of bumble bee colonies?
Authors: Holland Jacob G. , Nakayama Shinnosuke , Porfiri Maurizio , Nov Oded , Bloch Guy
Published: May 2020

Specialization and plasticity are important for many forms of collective behavior, but the interplay between these factors is little understood. In insect societies, workers are often predisposed to specialize in different tasks, sometimes with morphological or physiological adaptations, facilitating a division of labor. Workers may also plastically switch between tasks or vary their effort. The degree to which predisposed specialization limits plasticity is not clear and has not been systematically tested in ecologically relevant contexts. We addressed this question in 20 freely-foraging bumble bee (Bombus terrestris) colonies by continually manipulating colonies to contain either a typically diverse or reduced (“homogeneous”) worker body size distribution, over two trials. Pooling both trials, diverse colonies did better in several indices of colony performance. The importance of body size was further demonstrated by the finding that foragers were larger than nurses even in homogeneous colonies with a very narrow body size range. However, the overall effect of size diversity stemmed mostly from one trial. In the other trial, homogeneous and diverse colonies showed comparable performance. By comparing behavioral profiles based on several thousand observations, we found evidence that workers in homogeneous colonies in this trial rescued colony performance by plastically increasing behavioral specialization and/or individual effort, compared to same-sized individuals in diverse colonies. Our results are consistent with a benefit to colonies of predisposed (size-diverse) specialists under certain conditions, but also suggest that plasticity or effort, can compensate for reduced (size-related) specialization. Thus, we suggest that an intricate interplay between specialization and plasticity is functionally adaptive in bumble bee colonies.
Mycena genomes resolve the evolution of fungal bioluminescence
Authors: Ke Huei-Mien , Lee Hsin-Han , Lin Chan-Yi Ivy , Liu Yu-Ching , Lu Min R. , Hsieh Jo-Wei Allison , Chang Chiung-Chih , Wu Pei-Hsuan , Lu Meiyeh Jade , Li Jeng-Yi , Shang Gaus , Lu Rita Jui-Hsien , Nagy László G. , Chen Pao-Yang , Kao Hsiao-Wei , Tsai Isheng Jason
Published: May 2020

Mushroom-forming fungi in the order Agaricales represent an independent origin of bioluminescence in the tree of life, yet the diversity, evolutionary history, and timing of the origin of fungal luciferases remain elusive. We sequenced the genomes and transcriptomes of five bonnet mushroom species (Mycena spp.), a diverse lineage comprising the majority of bioluminescent fungi. Two species with haploid genome assemblies ∼150Mb are amongst the largest in Agaricales, and we found that a variety of repeats between Mycena species were differentially mediated by DNA methylation. We show that bioluminescence evolved in the last common ancestor of mycenoid and the marasmioid clade of Agaricales and was maintained through at least 160 million years of evolution. Analyses of synteny across genomes of bioluminescent species resolved how the luciferase cluster was derived by duplication and translocation, frequently rearranged and lost in most Mycena species, but conserved in the Armillaria lineage. Luciferase cluster members were co-expressed across developmental stages, with highest expression in fruiting body caps and stipes, suggesting fruiting-related adaptive functions. Our results contribute to understanding a de novo origin of bioluminescence and the corresponding gene cluster in a diverse group of enigmatic fungal species.

Significance

We present the genomes of five new bonnet mushroom Mycena species, formerly the last fungal bioluminescent lineage lacking reference genomes. These genome-scale datasets allowed us to construct an evolutionary model pinpointing all possible changes in the luciferase cluster across all fungi and additional genes involved in bioluminescence. We show that luciferase clusters were differentially lost in different fungal lineages and in particular a substantial loss was observed in the Mycena lineage. This can be attributed to genome regions of Mycena underwent different evolutionary dynamics. Our findings offer insights into the evolution of how a gene cluster that emerged 160 million years ago and was frequently lost or maintained due to differences in genome plasticity.
Identification of PDE6D as a potential target of sorafenib via PROTAC technology
Authors: Li Yang , Meng Qingshi , Wang Ping , Liu Xiaolei , Fu Qiuyu , Xie Yuting , Zhou Yu , Qi Xiangbing , Huang Niu
Published: May 2020

The identification of unknown target of a multi-kinase inhibitor sorafenib is important to better understand the mechanism of action of this drug in anti-cancer and anti-fibrotic treatments. Here, we report the combination of PROTAC technique with quantitative proteomic analysis to identify the unknown cellular targets of sorafenib. Sorafenib-based PROTAC can strongly degrade a non-kinase target PDEδ in different types of cells. We also confirmed the direct binding interaction of PDEδ with sorafenib by CETSA and SPR assays. Together, our research suggests that PDEδ is a new potential target of sorafenib, and PROTAC technology may be a promising approach for cellular target identification of bioactive compounds of interest.
Cutting out the middle clam: lucinid endosymbiotic bacteria are also associated with seagrass roots worldwide
Authors: Martin Belinda C. , Middleton Jen A. , Fraser Matthew W. , Marshall Ian P.G. , Scholz Vincent V. , Schmidt Hannes
Published: May 2020

Seagrasses and lucinid bivalves inhabit highly reduced sediments with elevated sulphide concentrations. Lucinids house symbiotic bacteria (Ca. Thiodiazotropha) capable of oxidising sediment sulphide, and their presence in sediments has been proposed to promote seagrass growth by decreasing otherwise phytotoxic sulphide levels. However, vast and productive seagrass meadows are present in ecosystems where lucinids do not occur. Hence, we hypothesised that seagrasses themselves host sulphur-oxidising bacteria that could secure their survival when lucinids are absent. We analysed newly generated and publicly available 16S rRNA gene sequences from seagrass roots and sediments across 14 seagrass species and 10 countries and found that persistent and colonising seagrasses across the world harbour sulphur-oxidisingCa. Thiodiazotropha, regardless of the presence of lucinids. We used fluorescencein situhybridisation to visually confirm the presence ofCa. Thiodiazotropha on roots ofHalophila ovalis, a colonising seagrass species with wide geographical, water depth range, and sedimentary sulphide concentrations. We provide the first evidence thatCa. Thiodiazotropha are commonly present on seagrass roots, providing a mechanism for seagrasses to alleviate sulphide stress globally.
Identification of Lipid Droplets in Gut Microbiota
Authors: Zhang Kai , Zhou Chang , Zhou Ziyun , Li Xuehan , Li Zemin , Zhang Mengwei , Zhang Xuelin , Zhang Congyan , Wei Taotao , Zhang Shuyan , Liu Pingsheng
Published: May 2020

Recent research has accumulating evidence to support that gut microbiota can be a newly discovered organ/tissue for humans. Although the functions of gut microbiota have been linked to almost all aspects of human physiological, most findings so far are still either belonged to correlational research or at preliminary stage of causal study due to the complexity of gut microbiota as well as lack of proper tools and methods. Thus, development of new approaches is essential and necessary. Lipid droplet is a cellular organelle governing cell lipid homeostasis that is directly related to human metabolic syndromes. Previously we and other groups found lipid droplets in several bacterial strains. We wonder if gut bacteria have lipid droplets. If so, these bacteria may play key roles to regulate gut lipid content, remove unnecessary lipids and produce useful lipid molecules for host. Here we identified lipid droplet-like structures in freshly isolated bacteria from mouse small and large intestines, as well as mouse and human feces. We also purified and analyzed lipid droplets from a cloned human gut bacteriumStreptomyces thermovulgaris. Together, we demonstrate the existence of lipid droplets in gut microbiota and established an approach to study them.
Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α
Authors: Al-Rashed Fatema , Ahmad Zunair , Thomas Reeby , Melhem Motasem , Snider Ashley J. , Obeid Lina M. , Al-Mulla Fahd , Hannun Yusuf A. , Ahmad Rasheed
Published: May 2020

Obesity is associated with elevated levels of TNF-α and proinflammatory CD11c monocytes /macrophages. TNF-α mediated dysregulation in the plasticity of monocytes/macrophages is concomitant with pathogenesis of several inflammatory diseases, including metabolic syndrome, but the underlying mechanisms are incompletely understood. Since neutral sphingomyelinase 2 (nSMase2; product of the sphingomyelin phosphodiesterase 3 gene,SMPD3) is a key enzyme for ceramide production involved in inflammation, we investigated whether nSMase2 contributed to the inflammatory changes in the monocytes/macrophages induced by TNF-α. In this study, we demonstrate that the disruption of nSMase activity in monocytes/macrophages either by chemical inhibitor GW4869 or small interfering RNA (siRNA) against SMPD3 results in defects in the TNF-α mediated expression of CD11c. Furthermore, blockage of nSMase in monocytes/macrophages inhibited the secretion of inflammatory mediators IL-1b and MCP-1. In contrast, inhibition of acid SMase (aSMase) activity did not attenuate CD11c expression or secretion of IL-1b and MCP-1. TNF-α-induced phosphorylation of JNK, p38 and NF-κB was also attenuated by the inhibition of nSMase2. Moreover, NF-kB/AP-1 activity was blocked by the inhibition of nSMase2. SMPD3 was elevated in PBMCs from obese individuals and positively corelated with TNF-α gene expression. These findings indicate that nSMase2 acts, at least in part, as a master switch in the TNF-α mediated inflammatory responses in monocytes/macrophages.
Dectin-1 limits central nervous system autoimmunity through a non-canonical pathway
Authors: Deerhake M. Elizabeth , Danzaki Keiko , Inoue Makoto , Cardakli Emre D. , Nonaka Toshiaki , Aggarwal Nupur , Barclay William E. , Ji Ru Rong , Shinohara Mari L.
Published: May 2020

Pathologic roles for innate immunity in neurologic disorders are well-described, but protective aspects of the immune response are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. However, we found that Dectin-1 is protective in experimental autoimmune encephalomyelitis (EAE), while its canonical signaling mediator, Card9, promotes the disease. Notably, Dectin-1 does not respond to heat-killedMycobacteria, an adjuvant to induce EAE. Myeloid cells mediate the protective function of Dectin-1 in EAE and upregulate gene expression of neuroprotective molecules, including Oncostatin M (Osm) through a non-canonical Card9-independent pathway, mediated by NFAT. Furthermore, we found that the Osm receptor (OsmR) functions specifically in astrocytes to reduce EAE severity. Our study revealed a new mechanism of protective myeloid-astrocyte crosstalk regulated by a non-canonical Dectin-1 pathway and identifies novel therapeutic targets for CNS autoimmunity.

Graphical Abstract

Dectin-1 is a protective C-type lectin receptor (CLR) in experimental autoimmune encephalomyelitis (EAE)

Dectin-1 promotes expression ofOsm, a neuroprotective IL-6 family cytokine, in myeloid cells

OsmR signaling in astrocytes limits EAE progression and promotes remission

Non-canonical Card9-independent signaling drives a distinct Dectin-1-mediated transcriptional program to induce expression ofOsmand other factors with protective or anti-inflammatory functions
A role for tectorial membrane mechanics in activating the cochlear amplifier
Authors: Nankali A. , Wang Y. , Strimbu C. E. , Olson E. S. , Grosh K.
Published: May 2020

The mechanical and electrical responses of the mammalian cochlea to acoustic stimuli are nonlinear and highly tuned in frequency. This is due to the electromechanical properties of cochlear outer hair cells (OHCs). At each location along the cochlear spiral, the OHCs mediate an active process in which the sensory tissue motion is enhanced at frequencies close to the most sensitive frequency (called the characteristic frequency CF). Previous experimental results showing an approximate 0.3 cycle phase shift in the OHC-generated extracellular voltage relative the basilar membrane displacement that is initiated at a frequency approximately one-half octave lower than the CF are repeated in the present paper with similar findings. This shift is significant because it brings the phase of the OHC-derived electromotile force near to that of the basilar membrane velocity at frequencies above the shift, thereby enabling the transfer of electrical to mechanical power at the basilar membrane. In order to seek a candidate physical mechanism for this phenomenon, we used a comprehensive electromechanical mathematical model of the cochlear response to sound. The model predicts the phase shift in the extracellular voltage referenced to the basilar membrane at a frequency approximately one-half octave below CF, in accordance with the experimental data. In the model, this feature arises from a minimum in the radial impedance of the tectorial membrane and its limbal attachment. These experimental and theoretical results are consistent with the hypothesis that a tectorial membrane resonance introduces the correct phasing between mechanical and electrical responses for power generation, effectively turning on the cochlear amplifier.

SIGNIFICANCE

The mechanical and electrical responses of the mammalian cochlea are nonlinear exhibiting up to a thousand-fold difference in gain depending on the frequency and level of sound stimulus. Cochlear outer hair cells (OHC) are broadband electro-mechanical energy converters that mediate this nonlinear active process. However, the mechanism by which the OHC electromotile force acquires the appropriate phase to power this nonlinearity remains unknown. By analyzing new and existing experimental data and using a mathematical model, we address this open issue. We present evidence which suggests that a relatively simple feature, the frequency dependence of the radial impedance of the tectorial membrane, provides requisite mechanics to turn on the frequency-specific nonlinear process essential for healthy hearing.
Interceptive capturing in large-billed crows: Velocity-dependent weighing of prediction of future target location and visual feedback of current target location
Authors: Ujihara Yusuke , Matsui Hiroshi , Izawa Ei-Ichi
Published: May 2020

Interception of a moving target is a fundamental behaviour of predators and requires tight coupling between the sensory and motor systems. In the literature of foraging studies, feedback mechanisms based on current target position are frequently reported. However, there have also been recent reports of animals employing feedforward mechanisms, in which prediction of future target location plays an important role. In nature, coordination of these two mechanisms may contribute to intercepting evasive prey. However, how animals weigh these two mechanisms remain poorly understood. Here, we conducted a behavioural experiment involving crows (which show flexible sensorimotor coordination in various domains) capturing a moving target. We changed the velocity of the target to examine how the crows utilised prediction of the target location. The analysis of moment-to-moment head movements and computational simulations revealed that the crows used prediction of future target location when the target velocity was high. In contrast, their interception depended on the current momentary position of the target when the target velocity was slow. These results suggest that crows successfully intercept targets by weighing predictive and visual feedback mechanisms, depending on the target velocity.
Spatially clustered resources increase aggregation and mating duration inDrosophila melanogaster
Authors: Churchill Emily R. , Bridle Jon R. , Thom Michael D. F.
Published: May 2020

In environments where females mate multiply, males should adjust their behaviour and physiology in response to the prevailing perceived level of sperm competition. This expectation is well supported by both laboratory and field studies, but we don’t yet know what mechanisms facilitate these plastic responses in natural populations. One way in which males appear to assess sperm competition risk is through encounter rates with conspecific males. Such encounter rates may be driven by the spatial distribution of resources required by male. However, explicit links between resource distribution, male encounter rate, and shifts in behaviour related to sperm competition have not been demonstrated. Here we show that a small increase in the distance of patches of food resources in the laboratory: (a) approximately halves the mean distances between pairs of males; and (b) is associated with an increase in subsequent copulation duration – previously shown to be a reliable indicator of male perception of sperm competition risk – by more than two minutes. Aggregation of resources, operating via increased encounter rate, is a mechanism that can stimulate plastic male sperm competition responses. Because spatial distribution of resources, including those exploited byDrosophila, is variable in nature, this may explain one way in which sperm competition-related plasticity is influenced in wild-living males.
VviMYB41 orthologs contribute to the water deficit induced suberization of grapevine fine roots
Authors: Zhang Li , Merlin Isabelle , Pascal Stéphanie , Bert Pierre-François , Domergue Frédéric , Gambetta Gregory A.
Published: May 2020

The permeability of roots to water and nutrients is controlled through a variety of mechanisms and one of the most conspicuous is the presence of structures such as the Casparian strips and suberin lamellae. Roots actively regulate the creation of these structures developmentally, along the length of the root, and in response to the environment, including abiotic stresses such as drought. In the current study, we characterized the suberin composition along the length of grapevine fine roots during development and in response to water deficit. In parallel samples we quantified changes in expression of suberin biosynthesis- and deposition-related gene families (via RNAseq) allowing the identification of drought-responsive suberin-related genes. Grapevine suberin composition did not differ between primary and lateral roots, and was similar to that of other species. Under water deficit there was a global upregulation of suberin biosynthesis which resulted in an increase of suberin specific monomers, but without changes in their relative abundances, and this upregulation took place across all the developmental stages of fine roots. These changes corresponded to the upregulation of numerous suberin biosynthesis- and deposition-related genes which included orthologs of the previously characterized AtMYB41 transcriptional factor. Functional validation of two grapevine MYB41 orthologs, VviMYB41 and VviMYB41-like, confirmed their ability to globally upregulate suberin biosynthesis and deposition. This study provides a detailed characterization of the developmental and water deficit induced suberization of grapevine fine roots and identifies important orthologs responsible for suberin biosynthesis, deposition, and its regulation in grape.

One sentence summary

Our study details the biochemical changes and molecular regulation of how grapevines decrease their root permeability during drought.
DMT alters cortical travelling waves
Authors: Alamia Andrea , Timmermann Christopher , VanRullen Rufin , Carhart-Harris Robin L.
Published: May 2020

Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) is a particularly interesting serotonergic psychedelic that can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. In the present study, we investigated the electrophysiological correlates of the DMT-induced altered state, by recording EEG signals from a pool of participants receiving DMT and (separately) placebo (saline), intravenously, while instructed to keep their eyes closed (i.e. ‘resting state’). Consistent with our prior hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e., travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest (i.e. a backward travelling wave) were significantly decreased, while the bottom-up ‘forward travelling wave’, was significantly increased. These results support a recent model proposing that psychedelics reduce the ‘precision-weighting of priors’, thus altering the balance of top-down versus bottom-up information passing, where properties of backward waves are considered correlates of this precision weighting. The robust hypothesis-confirming nature of the present findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states – i.e. reduced backward and increased forward travelling waves - and lend further support to prior assumptions about the functional significance of cortical travelling waves.
Binding Mechanism of the Matrix Domain of HIV-1 Gag on Lipid Membranes
Authors: Monje-Galvan V. , Voth Gregory A.
Published: May 2020

Aggregation of the HIV-1 Gag protein onto the plasma membrane (PM) enables viral budding and infection propagation. Gag assembly at the membrane interface is mediated by its matrix domain (MA), the Myristoylated (Myr) N-terminus. MA targets the PM through electrostatic interactions, mainly at its highly-basic-region (HBR). The mechanism of Myr insertion and its role in protein-membrane dynamics remains unclear. Using all-atom molecular dynamics, we examined an MA unit in the vicinity of lipid bilayers that model different characteristics of the PM. Interaction with PIP2and PS lipids is highly favored around the HBR, and is enough to keep the protein bound. Additionally, we simulated three MA units near our bilayers and quantified the collective effects of free monomers vs. formed trimers on Myr insertion events. Micro-second-long trajectories allowed us to observe Myr insertion, propose a mechanism, quantify specific interactions with lipids, and examine the response of the local membrane environment.
Haplocheck: Phylogeny-based Contamination Detection in Mitochondrial and Whole-Genome Sequencing Studies
Authors: Weissensteiner Hansi , Forer Lukas , Fendt Liane , Kheirkhah Azin , Salas Antonio , Kronenberg Florian , Schoenherr Sebastian
Published: May 2020

Within-species contamination is a major issue in sequencing studies, especially for mitochondrial studies. Contamination can be detected by analysing the nuclear genome or by inspecting the heteroplasmic sites in the mitochondrial genome. Existing methods using the nuclear genome are computationally expensive, and no suitable tool for detecting contamination in large-scale mitochondrial datasets is available. Here we present haplocheck, a tool that requires only the mitochondrial genome to detect contamination in both mitochondrial and whole-genome sequencing studies. Haplocheck is able to distinguish between contaminated and real heteroplasmic sites using the mitochondrial phylogeny. By applying haplocheck to the 1000 Genomes Project data, we show (1) high concordance in contamination estimates between mitochondrial and nuclear DNA and (2) quantify the impact of mitochondrial copy numbers on the mitochondrial based contamination results. Haplocheck complements leading nuclear DNA based contamination tools, and can therefore be used as a proxy tool in nuclear genome studies.

Haplocheck is available both as a command-line tool athttps://github.com/genepi/haplocheckand as a cloud web-service producing interactive reports that facilitates the navigation through the phylogeny of contaminated samples.
Epigenetic regulator miRNA pattern differences among SARS-CoV, SARS-CoV-2 and SARS-CoV-2 world-wide isolates delineated the mystery behind the epic pathogenicity and distinct clinical characteristics of pandemic COVID-19
Authors: Khan Md. Abdullah-Al-Kamran , Sany Md. Rabi Us , Islam Md. Shafiqul , Mehebub Md. Saheb , Khademul Islam Abul Bashar Mir Md.
Published: May 2020

Detailed molecular mechanism of SARS-CoV-2 pathogenesis is still elusive to address its deadlier nature and to design effective theraputics. Here, we present our study elucidating the interplay between the SARS-CoV and SARS-CoV-2 viruses’; and host’s miRNAs, an epigenetic regulator, as a mode of pathogenesis, and enlightened how the SARS-CoV and SARS-CoV-2 infections differ in terms of their miRNA mediated interactions with host and its implications in the disease complexity. We have utilized computational approaches to predict potential host and viral miRNAs, and their possible roles in different important functional pathways. We have identified several putative host antiviral miRNAs that can target the SARS viruses, and also SARS viruses’ encoded miRNAs targeting host genes.In silicopredicted targets were also integrated with SARS infected human cells microarray and RNA-seq gene expression data. Comparison of the host miRNA binding profiles on 67 different SARS-CoV-2 genomes from 24 different countries with respective country’s normalized death count surprisingly uncovered some miRNA clusters which are associated with increased death rates. We have found that induced cellular miRNAs can be both a boon and a bane to the host immunity, as they have possible roles in neutralizing the viral threat, parallelly, they can also function as proviral factors. On the other hand, from over representation analysis, interestingly our study revealed that although both SARS-CoV and SARS-CoV-2 viral miRNAs could target broad immune signaling pathways; only some of the SARS-CoV-2 miRNAs are found to uniquely target some immune signaling pathways like-autophagy, IFN-I signaling etc, which might suggest their immune-escape mechanisms for prolonged latency inside some hosts without any symptoms of COVID-19. Further, SARS-CoV-2 can modulate several important cellular pathways which might lead to the increased anomalies in patients with comorbidities like-cardiovascular diseases, diabetes, breathing complications, etc. This might suggest that miRNAs can be a key epigenetic modulator behind the overcomplications amongst the COVID-19 patients. Our results support that miRNAs of host and SARS-CoV-2 can indeed play a role in the pathogenesis which can be further concluded with more experiments. These results will also be useful in designing RNA therapeutics to alleviate the complications from COVID-19.
Identification of 370 genetic loci for age at first sex and birth linked to externalising behaviour
Authors: Mills Melinda C. , Tropf Felix C. , Brazel David M. , van Zuydam Natalie , Vaez Ahmad ,   eQTLGen Consortium, BIOS Consortium, Pers Tune H. , Snieder Harold , Perry John R.B. , Ong Ken K. , den Hoed Marcel , Barban Nicola , Day Felix R.
Published: May 2020

Age at first sexual intercourse (AFS) and age at first birth (AFB) have implications for health and evolutionary fitness. In the largest genome-wide association study to date (AFS, N=387,338; AFB, N=542,901), we identify 370 independent signals, 11 sex-specific, with a 5-6% polygenic score (PGS) prediction. Heritability of AFB shifted from 9% [CI=4-14] for women born in 1940 to 22% [CI=19-25] in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility, and spermatid differentiation. Polycystic Ovarian Syndrome leads to later AFB, linking with infertility. Late AFB is protective against later-life disease and associated with parental longevity. Higher childhood socioeconomic circumstances and those in the highest PGS decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, for understanding longevity, and guiding experimentation into mechanisms of infertility.
Dynamic patterns of YAP1 expression and cellular localization in the developing and injured utricle
Authors: Borse Vikrant , Barton Matthew , Arndt Harry , Kaur Tejbeer , Warchol Mark E.
Published: May 2020

The Hippo pathway is an evolutionarily conserved signaling pathway involved in regulating organ size, development, homeostasis and regeneration1–4. YAP1 is a transcriptional coactivator and the primary effector of Hippo signaling. Upstream activation of the Hippo pathway leads to nuclear translocation of YAP1, which then evokes changes in gene expression and cell cycle entry5. A prior study has demonstrated nuclear translocation of YAP1 in the supporting cells of the developing utricle6, but the possible role of YAP1 in hair cell regeneration is unclear. The present study characterizes the cellular localization of YAP1 in the utricles of mice and chicks, both under normal conditions and after hair cell injury. During neonatal development of the mouse utricle, YAP1 expression was observed in the cytoplasm of supporting cells, and was also transiently expressed in the cytoplasm of hair cells. We also observed temporary nuclear translocation of YAP1 in supporting cells of the mouse utricle at short time periods after placement in organotypic culture. However, little or no nuclear translocation of YAP1 was observed after injury to the utricles of neonatal or mature mice. In contrast, a significant degree of YAP1 nuclear translocation was observed in the chicken utricle after streptomycin-induced hair cell damagein vitroandin vivo. Together, these data suggest that differences in YAP1 signaling may be partly responsible for the distinct regenerative abilities of the avian vs. mammalian inner ear.
A Phylogenetic Approach to Inferring the Order in Which Mutations Arise during Cancer Progression
Authors: Gao Yuan , Gaither Jeff , Chifman Julia , Kubatko Laura
Published: May 2020

Summary

Although the role of evolutionary process in cancer progression is widely accepted, increasing attention is being given to the evolutionary mechanisms that can lead to differences in clinical outcome. Recent studies suggest that the temporal order in which somatic mutations accumulate during cancer progression is important. Single-cell sequencing provides a unique opportunity to examine the mutation order during cancer progression. However, the errors associated with single-cell sequencing complicate this task. We propose a new method for inferring the order in which somatic mutations arise within a tumor using noisy single-cell sequencing data that incorporates the errors that arise from the data collection process. Using simulation, we show that our method outperforms existing methods for identifying mutation order in most cases, especially when the number of cells is large. Our method also provides a means to quantify the uncertainty in the inferred mutation order along a fixed phylogeny. We apply our method to empirical data from colorectal and prostate cancer patients.
Taxonomic Reassignment ofPseudohaptolina Birgericomb. nov. (Haptophyta)
Authors: Gérikas Ribeiro Catherine , dos Santos Adriana Lopes , Probert Ian , Vaulot Daniel , Edvardsen Bente
Published: May 2020

The haptophyte genusPseudohaptolina(formerlyChrysochromulinaclade B1-3) currently harbors two species:Pseudohaptolina arcticaandPseudohap-tolina sorokinii. In addition,Chrysochromulina birgeriis expected to belong to this genus due to its morphological similarity toP. sorokinii, but has not yet been genetically characterized. A strain belonging toPseudohaptolinawas brought into culture from Arctic waters, characterized by 18S and 28S rRNA gene sequencing as well as optical and transmission electron microscopy, and deposited in the Roscoff Culture Collection with the code RCC5270. Molecular and morphological data from RCC5270 were compared with those from previously describedPseudohaptolinaandPseudohaptolina-like species. Strain RCC5270 showed strong phylogenetic affinity toP. sorokinii, but TEM observations showed that RCC5270 possesses three types of organic body scale, rather than two as originally described inP. sorokinii. We found that the occurrence of three scale types is likely to have been overlooked in the original descriptions of bothP. sorokiniiandC. birgeri. We also found that environmental metabarcodes identical to the sequence of RCC5270 were abundant in the location from whichC. birgeriwas initially described (Gulf of Finland). We conclude thatP. sorokiniiandC. birgeriare conspecific andP. sorokiniiis therefore synonymous withC. birgeri. Based on its phylogenetic placement and nomenclatural priority we propose the new combinationPseudohaptolina birgeriand emend the description of this species.