bluuebunny/crossref_metadata_2025 huggingface dataset:
Shaping the landscape ofN6-methyladenosine RNA methylation in Arabidopsis
Authors: Wong Chui Eng , Zhang Songyao , Xu Tao , Zhang Yu , Teo Zhi Wei Norman , Yan An , Shen Lisha , Yu Hao
Published: January 2023

N 6-methyladenosine (m6A) modification on messenger RNAs (mRNAs) is deposited by evolutionarily conserved methyltransferases (writers). How individual m6A writers sculpt the overall landscape of the m6A methylome and the resulting biological impact in multicellular organisms remains unknown. Here, we systematically surveyed the quantitative m6A methylomes at single-nucleotide resolution and their corresponding transcriptomes in Arabidopsis (Arabidopsis thaliana) bearing respective impaired m6A writers. The m6A sites associated with the five Arabidopsis writers were located mostly within 3′ untranslated regions with peaks at around 100 bp downstream of stop codons. m6A predominantly promoted the usage of distal poly(A) sites but had little effect on RNA splicing. Notably, impaired m6A writers resulted in hypomethylation and downregulation of transcripts encoding ribosomal proteins, indicating a possible correlation between m6A and protein translation. Besides the common effects on mRNA metabolism and biological functions uniquely exerted by different Arabidopsis m6A writers compared with their counterparts in human cell lines, our analyses also revealed the functional specificity of individual Arabidopsis m6A writers in plant development and response to stresses. Our findings thus reveal insights into the biological roles of various Arabidopsis m6A writers and their cognate counterparts in other multicellular m6A methyltransferase complexes.
Protectors in the Bermuda courts
Authors: Robinson Keith
Published: January 2023

Whilst the word itself appears very infrequently in Bermuda statute, the role of the protector has long featured in Bermuda trust practice and is often of great importance. This article outlines the statutory references to the office of Protector in Bermuda and then looks at some recent Bermuda cases where protectors were in issue, including where the Court has exercised its inherent jurisdiction to appoint and remove protectors. These cases show that the Court is willing to quickly intervene in the best interests of the beneficiaries.
Dysfunctional cerebello-cerebral network associated with vocal emotion recognition impairments
Authors: Thomasson Marine , Ceravolo Leonardo , Corradi-Dell’Acqua Corrado , Mantelli Amélie , Saj Arnaud , Assal Frédéric , Grandjean Didier , Péron Julie
Published: January 2023

Vocal emotion recognition, a key determinant to analyzing a speaker’s emotional state, is known to be impaired following cerebellar dysfunctions. Nevertheless, its possible functional integration in the large-scale brain network subtending emotional prosody recognition has yet to be explored. We administered an emotional prosody recognition task to patients with right versus left-hemispheric cerebellar lesions and a group of matched controls. We explored the lesional correlates of vocal emotion recognition in patients through a network-based analysis by combining a neuropsychological approach for lesion mapping with normative brain connectome data. Results revealed impaired recognition among patients for neutral or negative prosody, with poorer sadness recognition performances by patients with right cerebellar lesion. Network-based lesion-symptom mapping revealed that sadness recognition performances were linked to a network connecting the cerebellum with left frontal, temporal, and parietal cortices. Moreover, when focusing solely on a subgroup of patients with right cerebellar damage, sadness recognition performances were associated with a more restricted network connecting the cerebellum to the left parietal lobe. As the left hemisphere is known to be crucial for the processing of short segmental information, these results suggest that a corticocerebellar network operates on a fine temporal scale during vocal emotion decoding.
Risk assessment in the 21st century: where are we heading?
Authors: Brescia Susy , Alexander-White Camilla , Li Hequn , Cayley Alex
Published: January 2023

Reliance on animal tests for chemical safety assessment is increasingly being challenged, not only because of ethical reasons, but also because they procrastinate regulatory decisions and because of concerns over the transferability of results to humans. New approach methodologies (NAMs) need to be fit for purpose and new thinking is required to reconsider chemical legislation, validation of NAMs and opportunities to move away from animal tests. This article summarizes the presentations from a symposium at the 2022 Annual Congress of the British Toxicology Society on the topic of the future of chemical risk assessment in the 21st century. The symposium included three case-studies where NAMs have been used in safety assessments. The first case illustrated how read-across augmented with some in vitro tests could be used reliably to perform the risk assessment of analogues lacking data. The second case showed how specific bioactivity assays could identify an NAM point of departure (PoD) and how this could be translated through physiologically based kinetic modelling in an in vivo PoD for the risk assessment. The third case showed how adverse-outcome pathway (AOP) information, including molecular-initiating event and key events with their underlying data, established for certain chemicals could be used to produce an in silico model that is able to associate chemical features of an unstudied substance with specific AOPs or AOP networks. The manuscript presents the discussions that took place regarding the limitations and benefits of these new approaches, and what are the barriers and the opportunities for their increased use in regulatory decision making.
Venom-induced consumptive coagulopathy leading to thrombotic microangiopathy followingEchis carinatus sochurekibite: is snake antivenom effective?
Authors: Parihar Vivek , Mittal Aliza , Vikarn Vishwajeet , Didel Siyram , Singh Kuldeep
Published: January 2023

The incidence of thrombotic microangiopathy (TMA) following snake bite is reported to be ranging from 3.6 to 15%. We report a 10-year-old boy who developed TMA and due to venom-induced consumptive coagulopathy (VICC) despite receiving adequate and timely doses of snake antivenom following a bite of saw-scaled viper (Echis carinatus sochureki). VICC was managed by plasmapheresis. Though snake bite envenomation-associated renal complications are not uncommon, possibility of TMA should be considered early during management. Our patient developed TMA with subsequent acute cortical necrosis after saw-scaled viper bite despite an adequate and timely dose of snake antivenom which emphasizes the ineffectiveness of antivenom against the venom of given snake species leading to long-term complications.
Transurethral resection of bladder cancer with or without fluorescence
Authors: Horňák Jakub , Brisuda Antonín , Babjuk Marek
Published: January 2023

Purpose of review

Transurethral resection of bladder cancer (TURBT) is in its standard form an inherently imperfect technique. Fluorescence-guided photodynamic diagnosis (PDD) represents one way to improve the outcome by enhancing tumour detection. Fluorescence has been used in connection with bladder cancer since the 1970s, with a number of studies being published since then. However, the method is still not recommended as a standard part of TURBT mainly because of the limited level of evidence of concerned studies, questionable cost-effectiveness and even contradictory results. The review lists the latest articles covering this topic.

Recent findings

Several recently published meta-analyses reviewed a series of randomized controlled trials (RCTs) concerning PDD assisted TURBT. Results were generally supporting the positive effect on reduction of recurrence rate. However, the mentioned meta-analyses are overlapping in terms of reviewed RCT that provide only a low level of evidence according to a recent Cochrane review. Supposed limitations of PDD (timing of the procedure, low specificity) and possible solutions are also covered.

Most of the published data confirmed reduced early recurrence rate after PDD assisted TURBT comparing to standard TURBT. Its impact on late recurrence rate, progression rate or cost-effectiveness has not been sufficiently demonstrated.
Enhancing Safety of a System-Wide In Situ Simulation Program Using No-Go Considerations
Authors: Minors Anjoinette M. , Yusaf Tricia C. , Bentley Suzanne K. , Grueso Daisy , Campbell-Taylor Kimberly , Harford Marlene , Mehri Sepideh , Williams Lorren J. , Bajaj Komal
Published: January 2023

Introduction

A large-scale in situ simulation initiative on cardiac arrest in pregnancy was implemented across NYC Health + Hospitals. In situ simulation must be safely balanced with clinical conditions such as through application of no-go considerations or standardized reasons to cancel or postpone the simulation. Our objective is to describe our findings on the application of no-go considerations during this simulation initiative.

Methods

NYC Health + Hospitals/Simulation Center developed an in situ simulation program focused on cardiac arrest in pregnancy, implemented at 11 acute care facilities. The program's toolkit included no-go considerations for in situ simulation safety: situations prompting a need to cancel, reschedule, or postpone a simulation to ensure patient and/or staff safety.

Results

Data were collected from June 2018 through December 2019. The simulation sites reviewed the 13 established no-go considerations before each simulation event to assess if the simulation was safe to “go”. After the conclusion of the initiative, all data related to no-go considerations were analyzed.

Two hundred seventy-four in situ simulations were scheduled and 223 simulations (81%) were completed. Fifty-one no-go events were reported, with 78% identifying a reason by category. Twenty-two percent did not report a reason or category. Four of the 13 suggested no-go considerations were not reported.

Conclusions

The no-go considerations framework promotes standardized and strategic scheduling of in situ simulation. Analysis of no-go consideration application during this system-wide initiative provides a model for the usage of tracking no-go data to enhance safety and inform future simulation planning.
Noninvasive methods to monitor intracranial pressure
Authors: Dattilo Michael
Published: January 2023

Purpose of review

Intracranial pressure (ICP) is determined by the production of and outflow facility of cerebrospinal fluid. Since alterations in ICP are implicated in several vision-threatening and life-threatening diseases, measurement of ICP is necessary and common. All current clinical methods to measure ICP are invasive and carry the risk for significant side effects. Therefore, the development of accurate, reliable, objective, and portal noninvasive devices to measure ICP has the potential to change the practice of medicine. This review discusses recent advances and barriers to the clinical implementation of noninvasive devices to determine ICP.

Recent findings

Many noninvasive methods to determine ICP have been developed. Although most have significant limitations limiting their clinical utility, several noninvasive methods have shown strong correlations with invasively obtained ICP and have excellent potential to be developed further to accurately quantify ICP and ICP changes.

Although invasive methods remain the mainstay for ICP determination and monitoring, several noninvasive biomarkers have shown promise to quantitatively assess and monitor ICP. With further refinement and advancement of these techniques, it is highly possible that noninvasive methods will become more commonplace and may complement or even supplant invasively obtained methods to determine ICP in certain situations.
Effects of municipal boundaries measured by combining urban scaling and spatial interaction
Authors: Tordoir Pieter P. , van Raan Anthony F. J. , Poorthuis Ate
Published: January 2023

Urban scaling, the superlinear increase of socio-economic measures with increasing population, is a well-researched phenomenon. This article is focused on socio-economic performance scaling, which could possibly be driven by increasing returns of the size and density of interaction networks. If this is indeed the case, we should also find that spatial barriers to interaction affect scaling and cause local performance deviations. Possible barring effects of municipal boundaries are important from the perspective of urban and regional governance. We test the hypothesis of barring effects by correlating municipal boundaries with the structure of commuter networks within a large densely urbanized region, the Randstad in The Netherlands. The measured impacts of these boundaries are correlated with local employment-scaling deviations. Applying spatially weighted modelling techniques, we find that municipal borders have significant effects on inter-municipal commuting and indicate these effects on the map. The results show particularly significant correlations along dividing lines between large urban agglomerations and rural communities. The southern part of the Randstad is more fragmented by such dividing lines than the northern part, which could partly explain the diverging economic development between the two parts.
Noise facilitates entrainment of a population of uncoupled limit cycle oscillators
Authors: Kumpost Vojtech , Hilbert Lennart , Mikut Ralf
Published: January 2023

Many biological oscillators share two properties: they are subject to stochastic fluctuations (noise) and they must reliably adjust their period to changing environmental conditions (entrainment). While noise seems to distort the ability of single oscillators to entrain, in populations of uncoupled oscillators noise allows population-level entrainment for a wider range of input amplitudes and periods. Here, we investigate how this effect depends on the noise intensity and the number of oscillators in the population. We have found that, if a population consists of a sufficient number of oscillators, increasing noise intensity leads to faster entrainment after a phase change of the input signal (jet lag) and increases sensitivity to low-amplitude input signals.
A mitochondrion-free eukaryote contains proteins capable of import into an exogenous mitochondrion-related organelle
Authors: Fang Yi-Kai , Vaitová Zuzana , Hampl Vladimir
Published: January 2023

The endobiotic flagellate
Monocercomonoides exilis
is the only known eukaryote to have lost mitochondria and all its associated proteins in its evolutionary past. This final stage of the mitochondrial evolutionary pathway may serve as a model to explain events at their very beginning such as the initiation of protein import. We have assessed the capability of proteins from this eukaryote to enter emerging mitochondria using a specifically designed
in vitro
assay. Hydrogenosomes (reduced mitochondria) of
Trichomonas vaginalis
were incubated with a soluble protein pool derived from a cytosolic fraction of
M. exilis
, and proteins entering hydrogenosomes were subsequently detected by mass spectrometry. The assay detected 19 specifically and reproducibly imported proteins, and in 14 cases the import was confirmed by the overexpression of their tagged version in
T. vaginalis
. In most cases, only a small portion of the signal reached the hydrogenosomes, suggesting specific but inefficient transport. Most of these proteins represent enzymes of carbon metabolism, and none exhibited clear signatures of proteins targeted to hydrogenosomes or mitochondria, which is consistent with their inefficient import. The observed phenomenon may resemble a primaeval type of protein import which might play a role in the establishment of the organelle and shaping of its proteome in the initial stages of endosymbiosis.
Evolution of quantum non-equilibrium for coupled harmonic oscillators
Authors: Lustosa Francisco Bento , Pinto-Neto Nelson , Valentini Antony
Published: January 2023

In the context of de Broglie–Bohm pilot-wave theory, violations of the Born rule are allowed and can be considered as describing non-equilibrium distributions. We study the effects of interactions on quantum relaxation towards equilibrium for a system of one-dimensional coupled harmonic oscillators. We show by numerical simulations that interactions can delay or even prevent complete relaxation for some initial states. We also discuss how this effect might be relevant for cosmological scenarios and how non-equilibrium could be detected in some models.
Shear dilation of subglacial till results in time-dependent sliding laws
Authors: Warburton K. L. P. , Hewitt D. R. , Neufeld J. A.
Published: January 2023

The dynamics of glacial sliding over water-saturated tills are poorly constrained and difficult to capture realistically in large-scale models. Experiments characterize till as a plastic material with a pressure-dependent yield stress, but the subglacial water pressure may fluctuate on annual to daily timescales, leading to transient adjustment of the till. We construct a continuum two-phase model of coupled fluid and solid deformation, describing the movement of water through the pore space of a till that is itself dilating and deforming. By forcing the model with time-dependent effective pressure at the ice–till interface, we infer the resulting relationships between basal traction, solid fraction and rate of deformation. We find that shear dilation introduces internal pressure variations and transient dilatant strengthening emerges, leading to hysteretic behaviour in low-permeability materials. The result is a time-dependent effective sliding law, with permeability-dependent lag between changes in effective pressure and the slidingspeed. This deviation from traditional steady-state sliding laws may play an important role in a wide range of transient ice-sheet phenomena, from glacier surges to the tidal response of ice streams.
Survivorship dynamics of the flora of Devonian Angarida
Authors: Dowding Elizabeth M. , Akulov Nikolay Ivanovich , Mashchuk Irina Mikhailovna
Published: January 2023

Devonian plants in Siberia present protracted pioneer succession. Research into the survivorship dynamics of early plant communities upon the palaeocontinent Angarida have demonstrated that transgression and volcanogenic nutrient influx were key to the survival of colonizing plants. Taxic proportions show that migrating taxa entered Angarida from the southwest, Kuznetsk and Minusinsk basins, dispersing across the continent in waves through central areas northwards. The patterns of dispersal are consistent throughout the Devonian. Increased nutrient load from the active pulses of the Viluy-Yakutsk Large Igneous Province, biogeomorphic ecosystem engineering and the increased biomass of Angaridan plants are assisted by Late Devonian transgression. These cumulative factors can be linked to the Late Devonian marine extinctions observed in Siberia.
Inter-annual facilitation via pollinator support arises with species-specific germination rates in a model of plant–pollinator communities
Authors: James Aubrie R. M.
Published: January 2023

Facilitation is likely important for understanding community diversity dynamics, but its myriad potential mechanisms are under-investigated. Studies of pollinator-mediated facilitation in plants, for example, are typically focused on how co-flowering species facilitate each other's pollination within a season. However, pollinator-mediated facilitation could also arise in the form of inter-annual pollination support, where co-occurring plant populations mutually facilitate each other by providing dynamic stability to support a pollinator population through time. In this work, I test this hypothesis with simulation models of annual flowering plant and bee pollinator populations to determine if and how inter-annual pollination support affects the persistence and/or stability of simulated communities. Two-species plant communities persisted at higher rates than single-species communities, and facilitation was strongest in communities with low mean germination rates and highly species-specific responses to environmental variation. Single-species communities were often more stable than their counterparts, likely because of survivorship—persistent single-species communities were necessarily more stable through time to support pollinators. This work shows that competition and facilitation can simultaneously affect plant population dynamics. It also importantly identifies key features of annual plant communities that might exhibit inter-annual pollination support- those with low germination rates and species-specific responses to variation.
Phenological mismatches and the demography of solitary bees
Authors: Vázquez Diego P. , Vitale Nydia , Dorado Jimena , Amico Georgina , Stevani Erica L.
Published: January 2023

Species respond idiosyncratically to environmental variation, which may generate phenological mismatches. We assess the consequences of such mismatches for solitary bees. During 9 years, we studied flowering phenology and nesting phenology and demography of five wood-nesting solitary bee species representing a broad gradient of specialization/generalization in the use of floral resources. We found that the reproductive performance and population growth rate of bees tended to be lower with increasing nesting–flowering mismatches, except for the most generalized bee species. Our findings help elucidate the role of phenological mismatches for the demography of wild pollinators, which perform key ecosystem functions and provide important services for humanity. Furthermore, if climate change increases phenological mismatches in this system, we expect negative consequences of climate change for specialist bees.
Diversification dynamics in Caribbean rain frogs (Eleutherodactylus) are uncoupled from the anuran community and consistent with adaptive radiation
Authors: Jiménez-Ortega Dante , Valente Luis , Dugo-Cota Álvaro , Rabosky Daniel L. , Vilà Carles , Gonzalez-Voyer Alejandro
Published: January 2023

Adaptive radiation is proposed to play a key role in generating differences in species richness among lineages and geographical regions. Due to the importance of ecological divergence in adaptive radiation, species richness is predicted to be influenced by equilibrium diversity dynamics, although the concept continues to generate much debate. An additional important question is whether radiating clades have intrinsic biological characteristics that make them particularly prone to diversify. We tackle these questions by analysing (i) the temporal patterns of diversification of CaribbeanEleutherodactylusfrogs, and (ii) assembly of the complete native anuran community of the Caribbean archipelago (197 species), testing for the presence of equilibrium dynamics and whether diversification patterns ofEleutherodactylusdiffer from those of the rest of the Caribbean anurans. Diversification rates follow the predicted pattern of rapid diversification early in the radiation which gradually decreases towards the present.Eleutherodactylusdiversification is significantly faster than that of the Caribbean anuran community, and although equilibrium dynamics influence richness of all Caribbean anurans,Eleutherodactylusshows higher carrying capacity. Our results indicate that ecological opportunityper seis not sufficient for adaptive radiation and that diverse lineages present intrinsic characteristics that enable them to make the most of available opportunity.
Isochrony and rhythmic interaction in ape duetting
Authors: Raimondi Teresa , Di Panfilo Giovanni , Pasquali Matteo , Zarantonello Martina , Favaro Livio , Savini Tommaso , Gamba Marco , Ravignani Andrea
Published: January 2023

How did rhythm originate in humans, and other species? One cross-cultural universal, frequently found in human music, is isochrony: when note onsets repeat regularly like the ticking of a clock. Another universal consists in synchrony (e.g. when individuals coordinate their notes so that they are sung at the same time). An approach to biomusicology focuses on similarities and differences across species, trying to build phylogenies of musical traits. Here we test for the presence of, and a link between, isochrony and synchrony in a non-human animal. We focus on the songs of one of the few singing primates, the lar gibbon (
Hylobates lar
), extracting temporal features from their solo songs and duets. We show that another ape exhibits one rhythmic feature at the core of human musicality: isochrony. We show that an enhanced call rate overall boosts isochrony, suggesting that respiratory physiological constraints play a role in determining the song's rhythmic structure. However, call rate alone cannot explain the flexible isochrony we witness. Isochrony is plastic and modulated depending on the context of emission: gibbons are more isochronous when duetting than singing solo. We present evidence for rhythmic interaction: we find statistical causality between one individual's note onsets and the co-singer's onsets, and a higher than chance degree of synchrony in the duets. Finally, we find a sex-specific trade-off between individual isochrony and synchrony. Gibbon's plasticity for isochrony and rhythmic overlap may suggest a potential shared selective pressure for interactive vocal displays in singing primates. This pressure may have convergently shaped human and gibbon musicality while acting on a common neural primate substrate. Beyond humans, singing primates are promising models to understand how music and, specifically, a sense of rhythm originated in the primate phylogeny.
Growth in a biofilm promotes conjugation of ablaNDM-1-bearing plasmid betweenKlebsiella pneumoniaestrains
Authors: Element Sarah J. , Moran Robert A. , Beattie Emilie , Hall Rebecca J. , van Schaik Willem , Buckner Michelle M.C.
Published: January 2023

Antimicrobial resistance (AMR) is a growing problem, especially in Gram-negative Enterobacteriaceae such asKlebsiella pneumoniae. Horizontal transfer of conjugative plasmids contributes to AMR gene dissemination. Bacteria such asK. pneumoniaecommonly exist in biofilms, yet most studies focus on planktonic cultures. Here we studied the transfer of a multidrug resistance plasmid in planktonic and biofilm populations ofK. pneumoniae. We determined plasmid transfer from a clinical isolate, CPE16, which carried four plasmids, including the 119-kbpblaNDM-1-bearing F-type plasmid pCPE16_3, in planktonic and biofilm conditions. We found that transfer frequency of pCPE16_3 in a biofilm was orders-of-magnitude higher than between planktonic cells. In 5/7 sequenced transconjugants multiple plasmids had transferred. Plasmid acquisition had no detectable growth impact on transconjugants. Gene expression of the recipient and a transconjugant was investigated by RNA-sequencing in three lifestyles: planktonic exponential growth, planktonic stationary phase, and biofilm. We found that lifestyle had a substantial impact on chromosomal gene expression, and plasmid carriage affected chromosomal gene expression most in stationary planktonic and biofilm lifestyles. Furthermore, expression of plasmid genes was lifestyle-dependent, with unique signatures across the three conditions. Our study shows that growth in biofilm greatly increased the risk of conjugative transfer of a carbapenem resistance plasmid inK. pneumoniaewithout fitness costs and minimal transcriptional rearrangements, thus highlighting the importance of biofilms in the spread of AMR in this opportunistic pathogen.

Importance

Carbapenem-resistantK. pneumoniaeis particularly problematic in hospital settings. Carbapenem resistance genes can transfer between bacteria via plasmid conjugation. Alongside drug resistance,K. pneumoniaecan form biofilms on hospital surfaces, at infection sites and on implanted devices. Biofilms are naturally protected and can be inherently more tolerant to antimicrobials than their free-floating counterparts. There have been indications that plasmid transfer may be more likely in biofilm populations, thus creating a conjugation ‘hotspot’. However, there is no clear consensus on the effect of the biofilm lifestyle on plasmid transfer. Therefore, we aimed to explore the relationship between plasmid transfer and biofilms, and the impact of plasmid acquisition on the host bacterial cell. Our data show resistance plasmid transfer is greatly increased in a biofilm versus planktonic growth, which may be a significant contributing factor to the rapid dissemination of resistance plasmids inK. pneumoniae.
Harmonization of ICF Body Structures and ICD-11 Anatomic Detail: one foundation for two classifications
Authors: Mea Vincenzo Della , Almborg Ann-Helene , Martinuzzi Michela , Tu Samson W. , Martinuzzi Andrea
Published: January 2023

The Family of International Classifications of the World Health Organization currently includes three reference classifications, namely International Classification of Diseases (ICD), International Classification of Functioning, Disability, and Health (ICF), and International Classification of Health Interventions (ICHI). Each of them serves a specific classification need. However, they share some common concepts that are present, in different forms, in two or all of them. One important set of shared concepts is the representation of human anatomy entities, which are not always modeled in the same way and with the same level of detail. To understand the relationships among the three anatomical representations, an effort is needed to compare them, identifying common areas, gaps, and compatible and incompatible modeling. The work presented here contributes to this effort, focusing on the anatomy representations in ICF and ICD-11.

For this aim, three experts were asked to identify, for each entity in the ICF Body Structures, one or more entities in the ICD-11 Anatomic Detail that could be considered identical, broader or narrower. To do this, they used a specifically developed web application, which also automatically identified the most obvious equivalences.

A total of 631 maps were independently identified by the three mappers for 218 ICF Body Structures, with an interobserver agreement of 93.5%. Together with 113 maps identified by the software, they were then consolidated into 434 relations. The results highlight some differences between the two classifications: in general, ICF is less detailed than ICD-11; ICF favors lumping of structures; in very few cases, the two classifications follow different anatomic models. For these issues, solutions have to be found that are compliant with the WHO approach to classification modeling and maintenance.
Response to Tcherkez and Farquhar: Rubisco adaptation is more limited by phylogenetic constraint than by catalytic trade-off
Authors: Bouvier Jacques W. , Kelly Steven
Published: January 2023

Rubisco is the primary entry point for carbon into the biosphere. It has been widely proposed that rubisco is highly constrained by catalytic trade-offs due to correlations between the enzyme’s kinetic traits across species. In previous work, we have shown that these correlations, and thus the strength of catalytic trade-offs, have been over-estimated due to the presence of phylogenetic signal in the kinetic trait data (Bouvier et al., 2021). We demonstrated that only canonical trade-offs between the Michaelis constant for CO2and carboxylase turnover, and between the Michaelis constants for CO2and O2were robust to phylogenetic effects. We further demonstrated that phylogenetic constraints have limited rubisco adaptation to a greater extent than the combined action of catalytic trade-offs. Recently, however, our claims have been contested by Tcherkez and Farquhar (2021), who have argued that the phylogenetic signal we detect in rubisco kinetic traits is an artefact of species sampling, the use ofrbcL-basedtrees for phylogenetic inference, laboratory-to-laboratory variability in kinetic measurements, and homoplasy of the C4trait. In the present article, we respond to these criticisms on a point-by-point basis and conclusively show that all are either incorrect or invalid. As such, we stand by our original conclusions. Specifically, the magnitude of rubisco catalytic trade-offs have been overestimated in previous analyses due to phylogenetic biases, and rubisco kinetic evolution has in fact been more limited by phylogenetic constraint.
The influence of partner presence and association strength on neophobia in tokay geckos
Authors: Szabo Birgit , Ringler Eva
Published: January 2023

Neophobia, the avoidance of a novel stimulus, demonstrates the cognitive process of distinguishing novelty from familiarity. Different factors affect neophobia such as evolutionary background, cognitive skills or the social and non-social environment. Individuals from social species often change their neophobic response depending on the presence of a conspecific. Their response might even depend on their social relationship but the directionality of the change varies. To better understand the role of the social environment for neophobia, we tested the effect of the presence/ absence of a mating partner and pair association strength on neophobia across three contexts in the tokay gecko (Gekko gecko), a facultative social species with independent offspring. Geckos expressed neophobia similarly when housed singly and in pairs. However, we found that pairs that associated less entered a novel environment faster than those with a strong association while in pair housing. Our study adds important new insights into the relationship between social context and neophobia in a social lizard. Our results highlight that, even in species that express little affiliative behaviour, presence/ absence of a conspecific is insufficient to understand the complex relationship between the social environment and neophobia.
Introgressive Descent and Hypersexuality Drive The Evolution Of Sexual Parasitism and Morphological Reduction In a Fungal Species Complex
Authors: Fernández-Mendoza Fernando , Strasser Eva , Frolov Ivan , Vondrák Jan , Muggia Lucia , Mayrhofer Helmut , Gaya Ester , Grube Martin
Published: January 2023

Taxonomists consider species as discrete units of biological organization, which are subject to a continuous process of evolutionary change and are connected through their shared ancestry. However, the continuous nature of evolutionary change is difficult to reconcile with the discrete outcome of speciation, especially where species boundaries are permeable. A good example of this inconsistency is the lichen genusPyrenodesmia, which shows a high morphologic and genetic diversity that that defies systematization by taxonomic or phylogenetic methods. Here we show that hybridization explains the presence of discordant morphs and that European species are interconnected through cross-mating in a single reproductive network, a syngameon, despite which species remain largely distinct and distinguishable. Whole genome data reflect the important role played by genome defense mechanisms in the genomic stabilization of fungal hybrids. The recurrence of Repeat Induced Point mutations (RIP) shapes genomes with islands of suppressed recombination and loss of gene content, which in turn generates a feedback loop reinforcing the lack of reproductive isolation through the loss of heterokaryon incompatibility and a tendency towards morphological reduction.
Sensing of viral RNA in plants via a DICER-LIKE Ribonuclease
Authors: Nielsen Carsten Poul Skou , Han Lijuan , Arribas-Hernández Laura , Karelina Darya , Petersen Morten , Brodersen Peter
Published: January 2023

Sensors of intracellular double-stranded RNA are central components of metazoan innate antiviral immunity, but such sensors have not been identified in plants. RNA interference (RNAi) constitutes a potent plant antiviral defense mechanism that relies on conversion of viral RNA into small interfering RNAs by two DICER-LIKE (DCL) ribonucleases, DCL4 and DCL2. Here, we show that while plant DCL4 is dedicated to RNAi, cytoplasmic dicing by DCL2 also triggers RNAi-independent defense gene expression via at least two intracellular nucleotide-binding domain/leucine-rich repeat (NLR) immune receptors. CombinedDCL4/NLRinactivation abrogates basal resistance to a positive strand RNA virus. Our results redefine the basis of plant antiviral immunity, including autoimmunity as an explanation for DCL2-dependent growth arrest indcland RNA decay mutants in several plant species.

One sentence summary

The plant immune system uses Dicer-like ribonucleases for both antiviral RNA interference and double-stranded RNA sensing.
Carbohydrate distribution via SWEET17 is critical for Arabidopsis inflorescence branching under drought
Authors: Valifard Marzieh , Khan Azkia , Le Hir Rozenn , Pommerrenig Benjamin , Neuhaus H. Ekkehard , Keller Isabel
Published: January 2023

Sugars Will Eventually be Exported Transporters (SWEETs) are the most recently discovered family of plant sugar transporters. Functioning as uniporters and thus facilitating the diffusion of sugars across cell membranes, SWEETs play an important role in various physiological processes such as abiotic stress adaptation. AtSWEET17, a vacuolar fructose facilitator, was shown to be involved in the modulation of the root system during drought. Moreover, overexpression of a homolog from apple results in increased drought tolerance of tomato plants. Therefore, SWEET17 appears to be essential for the plant’s drought response. Nevertheless, the role and function of SWEET17 in aboveground tissues under drought stress to date remains enigmatic. By combining gene expression analysis with analysis of the sugar profile of various aboveground tissues, we uncovered a putative role of SWEET17 in the carbohydrate supply, and thus cauline branch emergence and growth, particularly during periods of carbon limitation as occurs under drought stress. SWEET17 thereby being of critical importance for maintaining efficient reproduction under drought stress.

Highlight

The fructose transporter SWEET17 supports shoot branching by increasing mobilization of carbohydrates from vacuoles to supply the newly forming inflorescence branch, thereby maintaining efficient reproduction under drought stress.
Streamlined Structure Determination by Cryo-Electron Tomography and Subtomogram Averaging using TomoBEAR
Authors: Balyschew Nikita , Yushkevich Artsemi , Mikirtumov Vasilii , Sanchez Ricardo M. , Sprink Thiemo , Kudryashev Misha
Published: January 2023

Structures of macromolecules in their native state provide unique unambiguous insights into their functions. Cryo-electron tomography combined with subtomogram averaging demonstrated the power to solve such structuresin situat resolutions in the range of 3 Angstrom for some macromolecules. In order to be applicable to structural determination of the majority of macromolecules observable in cells in limited amounts, processing of tomographic data has to be performed in a high-throughput manner. Here we present TomoBEAR - a modular configurable workflow engine for streamlined processing of cryo-electron tomographic data for subtomogram averaging. TomoBEAR combines commonly used cryo-EM packages and reasonable presets to provide a transparent “white box” for data management and processing. We demonstrate applications of TomoBEAR to two datasets of purified proteins and to a membrane protein RyR1 in a membrane and demonstrate the ability to produce high resolution with minimal human intervention. TomoBEAR is an open-source and extendable package, it will accelerate the adoption ofin situstructural biology by cryo-ET.
Disease-associated patterns of acetylation stabilize tau fibril formation
Authors: Li Li , Nguyen Binh , Mullapudi Vishruth , Saelices Lorena , Joachimiak Lukasz A.
Published: January 2023

Assembly of the microtubule-associated protein into tauopathy fibril conformations dictates the pathology of a diversity of diseases. Recent cryogenic Electron Microscopy (cryo-EM) structures have uncovered distinct fibril conformations in different tauopathies but it remains unknown how these structures fold from a single protein sequence. It has been proposed that post-translational modifications may drive tau assembly but no direct mechanism for how modifications drive assembly has emerged. Leveraging established aggregation-regulating tau fragments that are normally inert, we tested the effect of chemical modification of lysines with acetyl groups on tau fragment conversion into amyloid aggregates. We identify specific patterns of acetylation that flank amyloidogenic motifs on the tau fragments that drive rapid fibril assembly. To understand how this pattern of acetylation may drive assembly, we determined a 3.9 Å cryo-EM structure of an amyloid fibril assembled from an acetylated tau fragment. The structure uncovers how lysine acetylation patterns mediate gain-of-function interactions to promote amyloid assembly. Comparison of the structure to an ex vivo tau fibril conformation from Pick’s Disease reveals regions of high structural similarity. Finally, we show that our lysine- acetylated sequences exhibit fibril assembly activity in cell-based tau aggregation assays. Our data uncover the dual role of lysine residues in limiting aggregation while their acetylation leads to stabilizing pro-aggregation interactions. Design of tau sequence with specific acetylation patterns may lead to controllable tau aggregation to direct folding of tau into distinct folds.
Exploiting allele-specific transcriptional effects of subclonal copy number alterations for genotype-phenotype mapping in cancer cell populations
Authors: Shi Hongyu , Williams Marc J. , Satas Gryte , Weiner Adam C. , McPherson Andrew , Shah Sohrab P.
Published: January 2023

Somatic copy number alterations drive aberrant gene expression in cancer cells. In tumors with high levels of chromosomal instability, subclonal copy number alterations (CNAs) are a prevalent feature which often result in heterogeneous cancer cell populations with distinct phenotypes1. However, the extent to which subclonal CNAs contribute to clone-specific phenotypes remains poorly understood, in part due to the lack of methods to quantify how CNAs influence gene expression at a subclone level. We developed TreeAlign, which computationally integrates independently sampled single-cell DNA and RNA sequencing data from the same cell population and explicitly models gene dosage effects from subclonal alterations. We show through quantitative benchmarking data and application to human cancer data with single cell DNA and RNA libraries that TreeAlign accurately encodes clone-specific transcriptional effects of subclonal CNAs, the impact of allelic imbalance on allele-specific transcription, and obviates the need to arbitrarily define genotypic clones from a phylogenetic treea priori. Combined, these advances lead to highly granular definitions of clones with distinct copy-number driven expression programs with increased resolution and accuracy over competing methods. The resulting improvement in assignment of transcriptional phenotypes to genomic clones enables clone-clone gene expression comparisons and explicit inference of genes that are mechanistically altered through CNAs, and identification of expression programs that are genomically independent. Our approach sets the stage for dissecting the relative contribution of fixed genomic alterations and dynamic epigenetic processes on gene expression programs in cancer.
In situstructures of secretins from bacterial type II secretion system reveal their membrane interactions and translocation process
Authors: Yu Zhili , Wu Yaoming , Chen Muyuan , Huo Tong , Zheng Wei , Ludtke Steven J. , Shi Xiaodong , Wang Zhao
Published: January 2023

The GspD secretin is the outer membrane channel of the bacterial type II secretion system (T2SS) which secrets diverse effector proteins or toxins that cause severe diseases such as diarrhea and cholera. GspD needs to translocate from the inner to the outer membrane to exert its function, and this process is an essential step for T2SS to assemble. Here, we investigate two types of secretins discovered so far inEscherichia coli, GspDαand GspDβ, respectively. By electron cryotomography subtomogram averaging, we determinein situstructures of all the key intermediate states of GspDαand GspDβin the translocation process, with resolution ranging from 9 Å to 19 Å. In our results, GspDαand GspDβpresent entirely different membrane interaction patterns and ways of going across the peptidoglycan layer. We propose two distinct models for the membrane translocation of GspDαand GspDβ, providing a comprehensive perspective on the inner to outer membrane biogenesis of T2SS secretins.
How Occam’s razor guides human decision-making
Authors: Piasini Eugenio , Liu Shuze , Chaudhari Pratik , Balasubramanian Vijay , Gold Joshua I.
Published: January 2023

Occam’s razor is the principle that, all else being equal, simpler explanations should be preferred over more complex ones. This principle is thought to guide human decision-making, but the nature of this guidance is not known. Here we used preregistered behavioral experiments to show that people tend to prefer the simpler of two alternative explanations for uncertain data. These preferences match predictions of formal theories of model selection that penalize excessive flexibility. These penalties emerge when considering not just the best explanation but the integral over all possible, relevant explanations. We further show that these simplicity preferences persist in humans, but not in certain artificial neural networks, even when they are maladaptive. Our results imply that principled notions of statistical model selection, including integrating over possible, latent causes to avoid overfitting to noisy observations, may play a central role in human decision-making.
A general model for the evolution of nuptial gift-giving
Authors: Charmouh Anders P. , Bilde Trine , Bocedi Greta , Duthie A. Bradley
Published: January 2023

Nuptial gift-giving occurs in several taxonomic groups including insects, snails, birds, squid, arachnids and humans. Although this trait has evolved many times independently, no general framework has been developed to predict the conditions necessary for nuptial gift-giving to evolve. We use a time-in time-out model to derive analytical results describing the requirements necessary for selection to favour nuptial gift-giving. Specifically, selection will favour nuptial gift-giving if the fitness increase caused by gift-giving exceeds the product of expected gift search time and encounter rate of the opposite sex. Selection will favour choosiness in the opposite sex if the value of a nuptial gift exceeds the inverse of the time taken to produce offspring multiplied by the rate at which mates with nuptial gifts are encountered. Selection can differ between the sexes, potentially causing sexual conflict. We further investigate these results using an individual-based model inspired by a system of nuptial gift-giving spiders,Pisaura mirabilis, by estimating the fitness benefit of nuptial gift-giving using experimental data from several studies. Our results provide a general framework for understanding when the evolution of nuptial gift-giving can occur and provide novel insight into the evolution of worthless nuptial gifts, occurring in multiple taxonomic groups with implications for understanding parental investment.