bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment of a marine nematode model for animal functional genomics, environmental adaptation and developmental evolution
Authors: Xie Yusu , Zhang Pengchi , Xue Beining , Cao Xuwen , Ren Xiaoliang , Wang Lili , Sun Yuanyuan , Yang Hanwen , Zhang Liusuo
Published: March 2020

Nematodes play key roles in marine ecosystem. Although oceans cover 71% of the Earth’s surface, none of marine model nematode has been reported. Here, we constructed the first inbred line of free-living marine nematodeLitoditis marina, sequenced and assembled its genome. Furthermore, we successfully applied CRISPR/Cas9 genome editing inL. marina. Comparative genomics revealed that immunity and oxygen regulation genes are expanded, which is probably central to its sediment adaptation. WhileL. marinaexhibits massive gene contractions in NHRs, chemoreceptors, xenobiotics detoxification and core histones, which could explain the more defined marine environment. Our experiments showed that dozens of H4 genes inCaenorhabditis elegansmight contribute to its adaptation to the complex terrestrial environments, while two H4 genes inL. marinaare involved in salinity stress adaptation. Additionally, ninety-two conserved genes appear to be positively selected inL. marina, which may underpin its osmotic, neuronal and epigenetic changes in the sea. With short generation time, highly inbred lines, and genomic resources, our report bringsL. marinaa promising marine animal model, and a unique satellite marine model to the well-known biomedical model nematodeC. elegans. This study will underpin ongoing work on animal functional genomics, environmental adaptation and developmental evolution.
Wide awake at bedtime? The effects of caffeine on sleep and circadian timing in teenagers - a randomized crossover trial
Authors: Reichert Carolin F. , Veitz Simon , Bühler Miriam , Gruber Georg , Rehm Sophia S. , Rentsch Katharina , Garbazza Corrado , Meyer Martin , Slawik Helen , Lin Yu-Shiuan , Weibel Janine
Published: March 2020

Background

Adolescents frequently consume caffeine with unknown consequences on sleep and circadian rhythms. In adults, the evidence indicates that caffeine acutely reduces homeostatic sleep pressure and delays the circadian timing system.

Objective

Here, we investigated the acute effects of caffeine intake on the developing sleep-wake regulatory system of teenagers.

Design

In a double-blind randomized crossover laboratory study, 18 teenagers (16.1 ± 1 years old, pubertal development scale [PDS]: 2.76 ± 0.35) ingested 80 mg caffeine (vs placebo) four hours prior to bedtime. Until bedtime, participants regularly filled in the Karolinska Sleepiness Scale and gave saliva samples to measure melatonin secretion. During nighttime, we quantified homeostatic sleep need by the electroencephalographically derived amount of slow wave sleep duration (SWS). After sleep, participants rated sleep quality by the Leeds Sleep Evaluation Questionnaire.

Results

While participants felt less sleepy after caffeine vs. placebo (P=0.038), their ratings of sleep quality were not strongly affected by the treatment. However, objectively, SWS was on average reduced by ∼20 min after caffeine vs. placebo (P=0.026). This caffeine-induced reduction was more pronounced in those individuals with more SWS under placebo (regression:P=0.042; standardized beta=0.622,P=0.011), even if controlling for habitual caffeine intake or pubertal stage (PDS). In melatonin onsets we observed both delays and advances in response to caffeine. This variance could partly be explained by differences in relative dose (i.e., mg caffeine/kg of bodyweight): the higher the relative dose, the more likely were delays (regression:P=0.01; standardized beta=0.592,P=0.01).

Conclusions

In teenagers, evening caffeine intake of already 80 mg (i.e. ∼8fl oz of common energy drinks) is sufficient to promote alertness at the costs of subsequent sleep. These costs might be more pronounced in adolescents with a higher need for SWS. Moreover, caffeine might disturb the circadian timing system, consequently hampering the balanced interplay of sleep-wake regulatory components.

Sources of Support

Marie-Heim-Voegtlin Grant of the Swiss National Science Foundation (SNSF) PMPDP1_171364
Analyzing matched sets of microbiome data using the LDM and PERMANOVA
Authors: Zhu Zhengyi , Satten Glen A. , Mitchell Caroline , Hu Yi-Juan
Published: March 2020

Background

Matched-set data arise frequently in microbiome studies. For example, we may collect pre- and post-treatment samples from a set of individuals, or use important confounding variables to match data from case participants to one or more control participants. Thus, there is a need for statistical methods for data comprised of matched sets, to test hypotheses against traits of interest (e.g., clinical outcomes or environmental factors) at the community level and/or the OTU (operational taxonomic unit) level. Optimally, these methods should accommodate complex data such as those with unequal sample sizes cross sets, confounders varying within sets, as well as continuous traits of interest.

Methods

PERMANOVA is a commonly used distance-based method for testing hypotheses at the community level. We have also developed the linear decomposition model (LDM) that unifies the community-level and OTU-level tests into one framework. Here we present a strategy that can be used with both PERMANOVA and the LDM for analyzing matched-set data. We propose to include an indicator variable for each set as covariates, so as to constrain comparisons between samples within a set, and also permute traits within each set, which can account for exchangeable sample correlations. The flexible nature of PERMANOVA and the LDM allows discrete or continuous traits or interactions to be tested, within-set confounders to be adjusted, and unbalanced data to be fully exploited.

Results

Our simulations indicate that our proposed strategy outperformed alternative strategies in a wide range of scenarios. Using simulation, we also explored optimal designs for matched-set studies. The flexibility of PERMANOVA and the LDM for a variety of matched-set microbiome data is illustrated by the analysis of data from two real studies.

Conclusions

Including set indicator variables and permuting within sets when analyzing matched-set data with PERMANOVA or the LDM is a strategy that performs well and is capable of handling the complex data structures that frequently occur in microbiome studies.
Short-range, orientation-reversing template-switching events occur at a high frequency in the human and yeast genomes
Authors: Tremblay-Belzile Samuel , Di Giorgio Juliana Pérez , Loubert-Hudon Audrey , Verreault Alain , Brisson Normand , Omichinski James G.
Published: March 2020

The identification of structural variations in genomes using next-generation sequencing approaches greatly facilitates the study of genetic and genomic diseases. The data generated using these approaches also provide interesting new means to examine DNA repair, recombination, and replication to better understand sources of genomic instability. To better utilize this data, we developed SCARR (Systematic Combination of Alignments to Recreate Rearrangements) to identify DNA rearrangements, and used it to examine the occurrence of orientation-reversing events in human and budding yeast genomes. SCARR exceeds the sensitivity of previous genome sequencing approaches, and identifies rearrangements genome-wide with base-pair resolution, which helps provide insights into the mechanisms involved in their formation. We find that short-range orientation-reversing events occur at high rates in both human and yeast genomes. We quantified these rearrangements in yeast strains lacking various DNA repair factors, and propose that these short-range events often occur through template-switching events within a replication fork. We hypothesize that this mechanism may act as an error-prone alternative to fork reversal to restart stalled replication forks.
Combined abdominal heterotopic heart and aorta transplant model in mice
Authors: Dun Hao , Ye Li , Zhu Yuehui , Wong Brian W.
Published: March 2020

Abstract

Background

Allograft vasculopathy (AV) remains a major obstacle to long-term allograft survival. While the mouse aortic transplantation model has been proven as a useful tool for study of the pathogenesis of AV, simultaneous transplantation of the aorta alongside the transplantation of another organ may reveal more clinically relevant mechanisms that contribute to the pathogenesis of chronic allograft rejection. Therefore, we developed a combined abdominal heart and aorta transplantation model in mice which benefits from reducing animal and drug utilization, while providing an improved model to study the progressive nature of AV.

Methods

The middle of the infrarenal aorta of the recipient mouse was ligatured between the renal artery and its bifurcation. Proximal and distal aortotomies were performed at this site above and below the ligature, respectively, for the subsequent anastomoses of the donor aorta and heart grafts to the recipient infrarenal aorta in an end-to-side fashion. The distal anastomotic site of the recipient infrarenal aorta was connected with the outlet of the donor aorta. Uniquely, the proximal anastomotic site on the recipient infrarenal aorta was shared to connect with both the inlet of the donor aorta and the inflow tract to the donor heart. The outflow tract from the donor heart was connected to the recipient inferior vena cava (IVC).

Results

The median times for harvesting the heart graft, aorta graft, recipient preparation and anastomosis were 11.5, 8.0, 9.0 and 40.5 min, respectively, resulting in a total median ischemic time of 70 min. The surgery survival rate was more than 96% (29/30). Both the syngeneicC57Bl/6aorta and heart grafts survived more than 90 days in 29C57Bl/6recipients. Further,Balb/ctoC57Bl/6allografts treated with anti-CD40L and CTLA4.Ig survived more than 90 days with a 100% (3/3) survival rate. (3/3).

Conclusions

This model is presented as a new tool for researchers to investigate transplant immunology and assess immunosuppressive strategies. It is possible to share a common anastomotic stoma on the recipient abdominal aorta to reconstruct both the aorta graft entrance and heart graft inflow tract. This allows for the study of allogeneic effects on both the aorta and heart from the same animal in a single survival surgery.
Genome Report:De novogenome assembly and annotation for the Taita white-eye (Zosterops silvanus)
Authors: Engler Jan O. , Lawrie Yvonne , Gansemans Yannick , Van Nieuwerburgh Filip , Suh Alexander , Lens Luc
Published: March 2020

The Taita White-eye (Zosterops silvanus) is an endangered songbird endemic to the Taita Hills of Southern Kenya, where it is confined to small areas of fragmented forest. With diversification rates exceeding those reported in most other vertebrates, White-eyes are a prime example of a ‘great speciator’. Nevertheless, we still know surprisingly little about the genomic underpinnings leading to this extraordinary fast radiation. Here, we present a draft genome assembly (ZSil_MB_1.0) for the Taita White-eye generated from a blood sample of a wild, female bird captured in the Taita Hills, Kenya. By performing ade novoassembly with linked-reads and annotation of the assembly with the MAKER pipeline, we generated a 1.069 Gb assembly with a scaffold N50 of 1.105 Mb and an L50 of 244. After quality evaluation of the assembly, we identified 92.1% of BUSCOs complete or fragmented, indicating that ourde novoassembly is of high quality. This new assembly provides a genomic resource for future studies into the evolutionary and comparative genomics of this rapidly diversifying group of birds.
FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (OsFIT) interacts with OsIRO2 to regulate iron homeostasis
Authors: Liang Gang , Zhang Huimin , Li Yang , Pu Mengna , Yang Yujie , Li Chenyang , Lu Chengkai , Xu Peng , Yu Diqiu
Published: March 2020

There are two Fe-uptake strategies for maintaining Fe homeostasis in plants. As a special graminaceous plant, rice applies both strategies. However, it remains unclear how these two strategies are regulated in rice. IRON-RELATED BHLH TRANSCRIPTION FACTOR 2 (OsIRO2) is critical for regulating Fe uptake in rice. In this study, we identified an interacting partner of OsIRO2,Oryza sativaFER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (OsFIT), which encodes a bHLH transcription factor. The OsIRO2 protein is localized in the cytoplasm and nucleus, but OsFIT facilitates the accumulation of OsIRO2 in the nucleus. Loss-of-function mutations toOsFITresult in decreased Fe accumulation, severe Fe-deficiency symptoms, and disrupted expression of Fe-uptake genes. In contrast,OsFIToverexpression promotes Fe accumulation and the expression of Fe-uptake genes. Genetic analyses indicated thatOsFITandOsIRO2function in the same genetic node. Further analysis suggested that OsFIT and OsIRO2 form a functional transcription activation complex to initiate the expression of Fe-uptake genes. Our findings provide a mechanism understanding of how rice maintains Fe homeostasis.

One-sentence summary

OsFIT interacts with and facilitates the accumulation of OsIRO2 in the nucleus where the OsFIT-OsIRO2 transcription complex initiates the transcription of Fe deficiency responsive genes.
Single nucleus RNASeq profiling of mouse lung: reduced dissociation bias and improved detection of rare cell types compared with single cell RNASeq
Authors: Koenitzer Jeffrey R , Wu Haojia , Atkinson Jeffrey J , Brody Steven L , Humphreys Benjamin D
Published: March 2020

RATIONALE

Single cell RNA-sequencing (scRNASeq) has led to multiple recent advances in our understanding of lung biology and pathophysiology, but utility is limited by the need for fresh samples, loss of cell types due to death or inadequate dissociation, and the induction of transcriptional stress responses during tissue digestion. Single nucleus RNASeq (snRNASeq) has addressed these deficiencies in some other tissues, but no protocol exists for lung. We sought to develop such a protocol and compare its results with scRNA-seq.

METHODS

Single nucleus suspensions were prepared rapidly (45 min) from two mouse lungs in lysis buffer on ice while a single cell suspension from an additional mouse lung was generated using a combination of enzymatic and mechanical dissociation (1.5 h). Cells and nuclei were processed using the 10x Genomics platform, and following sequencing of cDNA libraries single cell data was analyzed by Seurat.

RESULTS

16,656 single nucleus and 11,934 single cell transcriptomes were generated. Despite reduced mRNA levels in nuclei vs. cells, gene detection rates were equivalent in snRNASeq and scRNASeq (∼1,750 genes and 3,000 UMI per cell) when mapping intronic and exonic reads. snRNASeq identified a much greater proportion of epithelial cells than scRNASeq (46% vs 2% of total), including basal and neuroendocrine cells, while reducing immune cells from 54% to 15%. snRNASeq transcripts are enriched for transcription factors and signaling proteins, with reduced detection of housekeeping genes, mitochondrial genes, and artifactual stress response genes. Both techniques improved mesenchymal cell detection over previous studies, and analysis of fibroblast diversity showed two transcriptionally distinct populations ofCol13a1+cells, termedBmper+andBrinp1+fibroblasts. To define homeostatic signaling relationships among cell types, receptor-ligand mapping of was performed for alveolar compartment cells using snRNASeq data, revealing complex interplay among epithelial, mesenchymal, and capillary endothelial cells.

CONCLUSION

Single nucleus RNASeq can be readily applied to snap frozen, archival murine lung samples, improves dissociation bias, eliminates artifactual gene expression and provides similar gene detection compared to scRNASeq.
Antibiotic prescribing records in two UK primary care electronic health record systems. Comparison of the CPRD GOLD and CPRD Aurum databases
Authors: Gulliford Martin C , Sun Xiaohui , Anjuman Thamina , Yelland Eleanor , Murray-Thomas Tarita
Published: March 2020

Objective

We evaluated whether recording of antibiotic prescribing across two primary care electronic health record (EHR) systems is similar. Data were analysed from the Clinical Practice Research Datalink (CPRD) databases: CPRD GOLD (Vision data) and CPRD Aurum (EMIS data).

Methods

Cohorts of patients were randomly sampled from both databases, stratifying by general practice, age-group and gender. All antibiotic prescriptions in 2017 were identified. Age- and sex-standardised antibiotic prescribing rates per 1,000 person years were calculated. Prescribing of individual antibiotic products and associated medical diagnosis recorded on the same date was also evaluated. English CPRD GOLD general practices were analysed as a subgroup, because all CPRD Aurum practices sampled were in England.

Results

There were 101,360 antibiotic prescriptions among 158,305 sampled patients at 883 CPRD Aurum practices, and 112,931 prescriptions among 160,394 sampled patients at 290 CPRD GOLD practices. The age- and sex-standardised antibiotic prescribing rate in 2017 was 512.6 (95% confidence interval 510.4 to 514.9) per 1,000 person years in CPRD Aurum and 584.3 (582.1 to 586.5) per 1,000 person years in CPRD GOLD [505.2 (501.6 to 508.9) per 1,000 person years if restricted to practices in England]. The 25 most frequently prescribed antibiotic products were similar in both databases. One or more medical codes were recorded on the same date as an antibiotic prescription for 72,989 (74%) prescriptions in CPRD Aurum, 84,756 (78%) in CPRD GOLD, and 28,471 (78%) for CPRD GOLD in England. Skin, respiratory and genito-urinary tract infections were recorded for 39,035 (40%) prescriptions in CPRD Aurum, 41,326 (38%) in CPRD GOLD, with 15,481 (42%) in English CPRD GOLD practices only.

Conclusion

Similar estimates for antibiotic prescribing and infection recording were found for both databases suggesting similar recording across EMIS and Vision systems. Future research on antimicrobial stewardship can be conducted in CPRD Aurum informed by previous results from CPRD GOLD. It may also be possible to combine CPRD GOLD and CPRD Aurum data in research on antibiotic prescribing.
Transmission potential of COVID-19 in Iran
Authors: Muniz-Rodriguez Kamalich , Fung Isaac Chun-Hai , Ferdosi Shayesteh R. , Ofori Sylvia K. , Lee Yiseul , Tariq Amna , Chowell Gerardo
Published: March 2020

We estimated the reproduction number of 2020 Iranian COVID-19 epidemic using two different methods: R0was estimated at 4.4 (95% CI, 3.9, 4.9) (generalized growth model) and 3.50 (1.28, 8.14) (epidemic doubling time) (February 19 - March 1) while the effective R was estimated at 1.55 (1.06, 2.57) (March 6-19).
Dopaminergic Co-transmission with Sonic Hedgehog Inhibits Abnormal Involuntary Movements
Authors: Malave Lauren , Zuelke Dustin R. , Uribe-Cano Santiago , Starikov Lev , Rebholz Heike , Friedman Eitan , Qin Chuan , Li Qin , Bezard Erwan , Kottmann Andreas H.
Published: March 2020

L-Dopa induced dyskinesia (LID) is a debilitating side effect of dopamine replacement therapy for Parkinson’s Disease. The mechanistic underpinnings of LID remain obscure. Here we report that diminshed sonic hedgehog (Shh) signaling in the basal ganglia caused by the degeneration of midbrain dopamine neurons (DANs) facilitates the formation and expression of LID. We demonstrate that augmenting Shh signaling with agonists of the Shh effector Smoothened attenuates LID in mouse and macaque models of PD. Employing conditional genetic loss-of-function approaches, we show that reducing Shh secretion from DANs or Smo activity in cholinergic interneurons (CINs) promotes LID. Conversely, the selective expression of constitutively active Smo (SmoM2) in CINs is sufficient to render the sensitized aphakia model of PD resistant to LID. Furthermore, acute depletion of Shh from DANs through prolonged optogenetic stimulation in otherwise intact mice and in the absence of L-Dopa produces LID-like involuntary movements. These findings indicate that augmenting Shh signaling in the L-Dopa treated brain may be a promising and unexpected novel therapeutic approach for mitigating the dyskinetic side effects of long-term treatment with L-Dopa
Detailed point cloud data on stem size and shape of Scots pine trees
Authors: Saarinen Ninni , Kankare Ville , Yrttimaa Tuomas , Viljanen Niko , Honkavaara Eija , Holopainen Markus , Hyyppä Juha , Huuskonen Saija , Hynynen Jari , Vastaranta Mikko
Published: March 2020

Quantitative assessment of the effects of forest management on tree size and shape has been challenging as there has been a lack of methodologies for characterizing differences and possible changes comprehensively in space and time. Terrestrial laser scanning (TLS) and photogrammetric point clouds provide three-dimensional (3D) information on tree stem reconstructions required for characterizing differences between stem shapes and growth allocation. This data set includes 3D reconstructions of stems of Scots pine (Pinus sylvestrisL.) trees from sample plots with different thinning treatments. The thinning treatments include two intensities of thinning, three thinning types as well as control (i.e. no thinning treatment since the establishment). The data set can be used in developing point clouds processing algorithms for single tree stem reconstruction and for investigating variation in stem size and shape of Scots pine trees. Additionally, it offers possibilities in characterizing the effects of various thinning treatments on stem size and shape of Scots pine trees from boreal forests.

Data set

Zenodohttps://zenodo.org/record/3701271

Data set license

Attribution 4.0 International (CC BY 4.0)
Association of lanthipeptide genes with TnpAREPtransposases in marine picocyanobacteria
Authors: Laurenceau Raphaël , Raho Nicolas , Cariani Zev , Bliem Christina , Kearney Sean M. , Thomas Elaina , Osman Mohammed A. M. , Chisholm Sallie W.
Published: March 2020

Lanthipeptides are a family of ribosomally synthesized, post-translationally modified peptides that are widespread among bacteria, typically functioning as antibacterials. The marine picocyanobacteriaProchlorococcusandSynechococcusproduce an unusual and diverse set of lanthipeptides of unknown function called prochlorosins. While well-studied model bacteria produce one or two different molecules of this type, a single picocyanobacterium can produce as many as 80; the community of picocyanobacteria in a single milliliter of seawater can collectively encode up to 10,000 prochlorosins. The molecular events that led to this expansion and diversification of the lanthipeptide repertoire in picocyanobacteria – the numerically dominant photosynthesizers in the oceans – is unknown.

We present evidence for an unusual association between prochlorosin genes with a single-stranded DNA transposase belonging to the TnpAREPfamily. The genes co-occur and co-localize across the phylogeny of marine picocyanobacteria forming a distinct association pattern within genomes, most likely resulting from the transposase activity. Given the role of TnpAREPhomologs in other bacteria, we propose - based on genomic structures - that they contribute to the creation of the prochlorosin structural diversity through a diversifying recombination mechanism.

Post-submission note

Since the original submission of this manuscript to bioRxiv, we have refined our phylogenetic analysis of the TnpA-REP transposases and we do not find strong evidence for or against a causal relationship between the presence of TnpA-REP transposases and the expansion and diversification of lanthipeptides genes. While the genetic association described in the manuscript remains valid, adjacent TnpA-REP and Prochlorosins do not appear phylogenetically linked, which might simply be the consequence of high rates of recombination for both genes. More genomic data are needed to untangle the driving force behind the lanthipeptide gene expansion in marine picocyanobacteria.

IMPORTANCE

Only a few mechanisms have been described that promote the diversification of a targeted gene region in bacteria. We present indirect evidence that the TnpAREPtransposases associated with prochlorosins in picocyanobacteria could represent a novel such mechanism, and explain the extreme expansion and diversification of prochlorosins in this abundant marine microbe.
Unravelling the Phylogenomic Relationships of the Most Diverse African Palm GenusRaphia(Calamoideae, Arecaceae)
Authors: Helmstetter Andrew J. , Kamga Suzanne Mogue , Bethune Kevin , Lautenschläger Thea , Zizka Alexander , Bacon Christine D. , Wieringa Jan J. , Stauffer Fred , Antonelli Alexandre , Sonké Bonaventure , Couvreur Thomas L.P.
Published: March 2020

Palms are conspicuous floristic elements across the tropics. In continental Africa, even though there are less than 70 documented species, they are omnipresent across the tropical landscape. The genusRaphiahas 20 accepted species in Africa and one species endemic to the Neotropics. It is the most economically important genus of African palms with most of its species producing food and construction material.Raphiais divided into five sections based on inflorescence morphology. Nevertheless, the taxonomy ofRaphiais problematic with no intra-generic phylogenetic study available. We present a phylogenetic study of the genus using a targeted exon capture approach sequencing of 56 individuals representing 18 out of the 21 species. Our results recovered five well supported clades within the genus. Three sections correspond to those based on inflorescence morphology.R. regalisis strongly supported as sister to all otherRaphiaspecies and is placed into a newly described section: Erectae. Overall, morphological based identifications agreed well with our phylogenetic analyses, with 12 species recovered as monophyletic based on our sampling. Species delimitation analyses recovered 17 or 23 species depending on the confidence level used. Species delimitation is especially problematic in the Raphiate and Temulentae sections. In addition, our clustering analysis using SNP data suggested that individual clusters matched geographic distribution. The Neotropical speciesR. taedigerais supported as a distinct species, rejecting the hypothesis of a recent introduction into South America. Our analyses support the hypothesis that theRaphiaindividuals from Madagascar are potentially a distinct species different from the widely distributedR. farinifera. In conclusion, our results support the infra generic classification ofRaphiabased on inflorescence morphology, which is shown to be phylogenetically useful. Classification and species delimitation within sections remains problematic even with our phylogenomic approach. Certain widely distributed species could potentially contain cryptic species. More in-depth studies should be undertaken using morphometrics, increased sampling and more variable markers. Our study provides a robust phylogenomic framework that enables further investigation on the biogeographic history, morphological evolution and other eco-evolutionary aspects of this charismatic, socially and economically important palm genus.
Effects of dead conspecifics, hunger states, and seasons on the foraging behavior of the purple urchinHeliocidaris crassispina
Authors: Belleza Dominic Franco C. , Kawabata Yuuki , Toda Tatsuki , Nishihara Gregory N.
Published: March 2020

Trophic cascades exerts a powerful effect between predator and prey relationships in an ecosystem. In aquatic environments, the signals associated with predators and predation are used by prey as a cue to avoid encountering predators when foraging for food. These cues are powerful enough to control prey populations and indirectly protect primary producers. We evaluated the effects of cues associated with predation on the purple urchin,Heliocidariscrassispina and examined effects of hunger state and season using time-lapse photography, we conducted a series of manipulative andin situbehavior experiments to determine foraging behavior patterns which demonstrate behavior modification. The results suggest that starved urchins were less sensitive to predation cues when compared to normally fed urchins. Field experiments indicated that 70% of fed urchins fled when exposed to a predation cue (presence of a dead urchin), whereas all starved urchins remained regardless of the cue, supporting the results from the laboratory using the dead urchin and algae treatment cues. Sea urchin activity and feeding rates were lower in winter-spring than in summer-autumn. We suggest that hunger state has a large influence over the behavioral-response of sea urchins, while also being affected by season due to metabolic control. In general, starvation overrides predator avoidance behaviors and exposes prey species to higher risks of predation.
Sister-chromatid-sensitive Hi-C reveals the conformation of replicated human chromosomes
Authors: Mitter Michael , Gasser Catherina , Takacs Zsuzsanna , Langer Christoph C. H. , Tang Wen , Jessberger Gregor , Beales Charlie T. , Neuner Eva , Ameres Stefan L. , Peters Jan-Michael , Goloborodko Anton , Micura Ronald , Gerlich Daniel W.
Published: March 2020

The three-dimensional organization of the genome supports regulated gene expression, recombination, DNA repair, and chromosome segregation during mitosis. Chromosome conformation capture (Hi-C)1–3has revealed a complex genomic landscape of internal chromosome structures in vertebrate cells4–11yet how sister chromatids topologically interact in replicated chromosomes has remained elusive due to their identical sequences. Here, we present sister-chromatid-sensitive Hi-C (scsHi-C) based on nascent DNA labeling with 4-thio-thymidine. Genome-wide conformation maps of human chromosomes revealed that sister chromatid pairs interact most frequently at the boundaries of topologically associating domains (TADs). Continuous loading of a dynamic cohesin pool separates sister-chromatid pairs inside TADs and is required to focus sister chromatid contacts at TAD boundaries. We identified a subset of TADs that are overall highly paired, characterized by facultative heterochromatin, as well as insulated topological domains that form separately within individual sister chromatids. The rich pattern of sister chromatid topologies and our scsHi-C technology will make it possible to dissect how physical interactions between identical DNA molecules contribute to DNA repair, gene expression, chromosome segregation, and potentially other biological processes.
The time course of chromatic adaptation under immersive illumination
Authors: Gupta Gaurav , Gross Naomi , Pastilha Ruben , Hurlbert Anya
Published: March 2020

Chromatic adaptation is a major contributory mechanism to constancy, yet its extent depends on many factors - spectral, spatial and temporal - which vary between studies and hence may contribute to differences in reported constancy indices. Here, we use the achromatic adjustment method to characterise the temporal progression of chromatic adaptation under a wide range of illuminations in an immersive environment. We control both the spectral properties of the illumination at the eye and the spatial context of the adjusted surface, to disentangle global adaptation from local contrast effects. We measure the timecourse of chromatic adaptation by assessing achromatic adjustments in 6 discrete time slots over 340 seconds. We find that the change over time of the adaptation state, proximally indicated by colour constancy indices (quantified by the relative closeness of the perceptual whitepoint to the test illumination chromaticity), (a) can be modelled by a proportional rate growth function, typically requiring more than 5 minutes to stabilise; (b) depends on the contrast between the test surface and its background, specifically increasing with decreasing test-background contrast; and (c) is generally similar in both extent and rate for different test illumination chromaticities. Adaptation progression does not differ significantly between illuminations on or off the daylight locus. Our results highlight the importance of considering exposure duration and stimulus configuration, as well as the distance between the pre-adaptation (reference) and test illumination chromaticities, when using achromatic adjustment as a measure of colour constancy.
Oscillatory and aperiodic neural activity jointly predict language learning
Authors: Cross Zachariah R. , Corcoran Andrew W. , Schlesewsky Matthias , Kohler Mark. J. , Bornkessel-Schlesewsky Ina
Published: March 2020

Memory formation involves the synchronous firing of neurons in task-relevant networks, with recent models postulating that a decrease in low frequency oscillatory activity underlies successful memory encoding and retrieval. However, to date, this relationship has been investigated primarily with face and image stimuli; considerably less is known about the oscillatory correlates of complex rule learning, as in language. Further, recent work has shown that non-oscillatory (1/f) activity is functionally relevant to cognition, yet its interaction with oscillatory activity during complex rule learning remains unknown. Using spectral decomposition and power-law exponent estimation of human EEG data (17 females, 18 males), we show for the first time that 1/fand oscillatory activity jointly influence the learning of word order rules of a miniature artificial language system. Flexible word order rules were associated with a steeper 1/fslope, while fixed word order rules were associated with a shallower slope. We also show that increased theta and alpha power predicts fixed relative to flexible word order rule learning and behavioural performance. Together, these results suggest that 1/factivity plays an important role in higher-order cognition, including language processing, and that grammar learning is modulated by different word order permutations, which manifest in distinct oscillatory profiles.
Nucleo-plastidic PAP8/pTAC6 couples chloroplast formation with photomorphogenesis
Authors: Liebers Monique , Gillet François-Xavier , Israel Abir , Pounot Kevin , Chambon Louise , Chieb Maha , Chevalier Fabien , Ruedas Rémi , Favier Adrien , Gans Pierre , Erba Elisabetta Boeri , Cobessi David , Pfannschmidt Thomas , Blanvillain Robert
Published: March 2020

The initial greening of angiosperm occurs upon light-activation of photoreceptors that trigger photomorphogenesis followed with the development of chloroplasts. In these semi-autonomous organelles, the construction of the photosynthetic apparatus depends on the coordination of nuclear and plastid gene expression. Here we show that PAP8, as an essential subunit of the plastid-encoded RNA polymerase, is under the control of a regulatory element recognized by the photomorphogenic factor HY5. PAP8 is localized and active in both plastids and the nucleus and particularly essential for the formation of late photobodies. In the albinopap8mutant, phytochrome-mediated signalling is altered, PIFs are maintained, HY5 is not stabilized, and GLK1 expression is impaired. PAP8 translocates into plastids losing its pre-sequence, interacts with the PEP, and using an unknown route or a retrograde transport, reaches the nucleus where it has the ability to interact with pTAC12/HMR/PAP5. Since PAP8 is required for the phytochrome-B-mediated signalling cascade and the reshaping of the PEP, it may coordinate nuclear gene expression with the PEP-driven chloroplastic gene expression during chloroplast biogenesis.
Disentangling primer interactions improves SARS-CoV-2 genome sequencing by the ARTIC Network’s multiplex PCR
Authors: Itokawa Kentaro , Sekizuka Tsuyoshi , Hashino Masanori , Tanaka Rina , Kuroda Makoto
Published: March 2020

Since December 2019, the coronavirus disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2 has rapidly spread to almost every nation in the world. Soon after the pandemic was recognized by epidemiologists, a group of biologists comprising the ARTIC Network, has devised a multiplexed polymerase chain reaction (PCR) protocol and primer set for targeted whole-genome amplification of SARS-CoV-2. The ARTIC primer set amplifies 98 amplicons, which are separated only in two PCRs, across a nearly entire viral genome. The original primer set and protocol showed a fairly small amplification bias when clinical samples with relatively high viral loads were used. However, when sample’s viral load was low, several amplicons, especially amplicons 18 and 76, exhibited low coverage or complete dropout. We have determined that these dropouts were due to a dimer formation between the forward primer for amplicon 18, 18_LEFT, and the reverse primer for amplicon 76, 76_RIGHT. Replacement of 76_RIGHT with an alternatively designed primer was sufficient to produce a drastic improvement in coverage of both amplicons. Based on this result, we replaced 12 primers in total in the ARTIC primer set that were predicted to be involved in 14 primer interactions. The resulting primer set, version N1 (NIID-1), exhibits improved overall coverage compared to the ARTIC Network’s original (V1) and modified (V3) primer set.
Repeatable ecological dynamics govern response of experimental community to antibiotic pulse perturbation
Authors: Cairns Johannes , Jokela Roosa , Becks Lutz , Mustonen Ville , Hiltunen Teppo
Published: March 2020

In an era of pervasive anthropogenic ecological disturbances, there is a pressing need to understand the factors constituting community response and resilience. A detailed understanding of disturbance response needs to go beyond associations and incorporate features of disturbances, species traits, rapid evolution and dispersal. Multispecies microbial communities experiencing antibiotic perturbation represent a key system with important medical dimensions. However, previous microbiome studies on the theme have relied on high-throughput sequencing data from uncultured species without the ability to explicitly account for the role of species traits and immigration. Here we serially passaged a 34-species defined bacterial community through different levels of pulse antibiotic disturbance, manipulating the presence or absence of species immigration. To understand the ecological community response measured by amplicon sequencing, we combined initial trait data measured for each species separately and metagenome sequencing data revealing adaptive mutations during the experiment. We found that the ecological community response was highly repeatable within the experimental treatments, owing to an increasingly strong yet canalized response at increasing antibiotic levels, which could be partly attributed to key species traits (antibiotic susceptibility and growth rate). Increasing antibiotic levels were also coupled with increasing species extinction probability, making species immigration preventing this critical for community resilience. Moreover, we could detect signals of antibiotic resistance evolution occurring within species at the same time scale, leaving evolutionary changes in communities despite recovery at the species compositional level. Together these observations reveal a disturbance response which appears as classic species sorting but is nevertheless accompanied by rapid within-species evolution.
The periphery is the dominant site of B-cell deletion in a polyclonal repertoire
Authors: Brooks Jeremy F. , Steptoe Raymond J.
Published: March 2020

The concerted actions of multiple tolerance checkpoints limit the possibility of immune attack against self-antigens. For B cells, purging of autoreactivity from the developing repertoire has been almost exclusively studied using B-cell receptor transgenic models. Analyses have generally agreed that central and peripheral tolerance occurs in the form of deletion, receptor editing and anergy. However, when and where these processes occur in a normal polyclonal repertoire devoid of B-cell receptor engineering remain unclear. Here, employing sensitive tools that alleviate the need for B-cell receptor engineering, we track the development of self-reactive B cells and challenge whether deletion plays a meaningful role in B-cell tolerance. We find self-reactive B cells can mature unperturbed by ubiquitous self-antigen expression but, even in the presence of T-cell help, are robustly anergic in the periphery. These studies query the prominence attributed to central and peripheral deletion by most BCR transgenic studies and suggest that other mechanisms predominantly govern B cell tolerance.
Unravelling Representations in Scene-selective Brain Regions Using Scene Parsing Deep Neural Networks
Authors: Dwivedi Kshitij , Martin Cichy Radoslaw , Roig Gemma
Published: March 2020

Visual scene perception is mediated by a set of cortical regions that respond preferentially to images of scenes, including the occipital place area (OPA) and parahippocampal place area (PPA). However, the differential contribution of OPA and PPA to scene perception remains an open research question. In this study, we take a deep neural network (DNN)-based computational approach to investigate the differences in OPA and PPA function. In a first step we search for a computational model that predicts fMRI responses to scenes in OPA and PPA well. We find that DNNs trained to predict scene components (e.g., wall, ceiling, floor) explain higher variance uniquely in OPA and PPA than a DNN trained to predict scene category (e.g., bathroom, kitchen, office). This result is robust across several DNN architectures. On this basis, we then determine whether particular scene components predicted by DNNs differentially account for unique variance in OPA and PPA. We find that variance in OPA responses uniquely explained by the navigation-related floor component is higher compared to the variance explained by the wall and ceiling components. In contrast, PPA responses are better explained by the combination of wall and floor, that is scene components that together contain the structure and texture of the scene. This differential sensitivity to scene components suggests differential functions of OPA and PPA in scene processing. Moreover, our results further highlight the potential of the proposed computational approach as a general tool in the investigation of the neural basis of human scene perception.
The design and implementation of restraint devices for the injection of pathogenic microorganisms intoGalleria mellonella
Authors: Fredericks Lance R. , Roslund Cooper R. , Lee Mark D. , Crabtree Angela M. , Allen Peter B. , Rowley Paul A.
Published: March 2020

The injection of laboratory animals with pathogenic microorganisms poses a significant safety risk because of the potential for injury by accidental needlestick. This is especially true for researchers using invertebrate models of disease due to the small size of the animals and the required precision and accuracy of the injection. The immobilization of the greater wax moth larvae (Galleria mellonella) is often achieved by grasping a larva firmly between finger and thumb. Needle resistant gloves or forceps can be used to reduce the risk of a needlestick but can result in animal injury, a loss of throughput, and inconsistencies in experimental data. Immobilization devices are commonly used for the manipulation of small mammals, and in this manuscript, we describe the construction of injection chambers that can be used to entrap and restrainG. mellonellalarvae prior to injection with pathogenic microbes. These devices significantly reduce the manual handling of larvae and provide an engineering control to protection against accidental needlestick injury, while maintaining a high rate of injection.
Dissecting the role of Amerindian genetic ancestry andApoEε4 allele on Alzheimer disease in an admixed Peruvian population
Authors: Cornejo-Olivas M. , Rajabli F. , Marca V. , Whitehead P.G. , Hofmann N. , Ortega O. , Milla-Neyra K. , Veliz-Otani D. , Custodio N. , Montesinos R. , Castro-Suarez S. , Meza M. , Adams L.D. , Mena P.R. , Isasi R. , Cuccaro M.L. , Vance J.M. , Beecham G.W. , Mazzetti P. , Pericak-Vance M.A.
Published: March 2020

Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups.ApoE ε4is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic White populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation inε4risk is correlated with the genetic ancestral background local to theApoEgene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ∼80 of Amerindian ancestry provides a unique opportunity to assess the role of Amerindian ancestry in Alzheimer disease. In this study we assess the effect of theApoEε4 allele on AD in the Peruvian population.

A total of 78 AD cases and 128 unrelated cognitive healthy controls were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array. Global ancestry and local ancestry analyses were assessed. The effect of theApoE ε4allele on Alzheimer disease was tested using a logistic regression model by adjusting for age, gender, and population substructure (first three principal components). Logistic regression results showed thatApoE ε4allele is significantly associated with AD in Peruvian population with the high-risk effect (OR = 5.02, CI: 2.3-12.5, p-value = 2e-4). The average values of the local ancestries surrounding theApoEgene (chr19:44Mb-46Mb) have the highest proportion of Amerindian (60.6%), followed by European (33.9%) and African (5.5%) ancestral backgrounds.

Our results showed that the risk for AD fromApoE ε4in Peruvians is higher than we have observed in non-Hispanic White populations. Given the high admixture of Amerindian ancestry in the Peruvian population, it suggests that the Amerindian local ancestry is contributing to a strong risk for AD inApoEε4 carriers. Our data also support the findings of an interaction between the genetic risk alleleApoE ε4and the ancestral backgrounds located around the genomic region ofApoEgene.