bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular architecture and oligomerization of Candida glabrata Cdc13 underpin its telomeric DNA-binding and unfolding activity
Authors: Coloma Javier , Gonzalez-Rodriguez Nayim , Balaguer Francisco A , Gmurczyk Karolina , Aicart-Ramos Clara , Nuero Óscar M , Luque-Ortega Juan Román , Calugaru Kimberly , Lue Neal F , Moreno-Herrero Fernando , Llorca Oscar 
Published: January 2023

Abstract
The CST complex is a key player in telomere replication and stability, which in yeast comprises Cdc13, Stn1 and Ten1. While Stn1 and Ten1 are very well conserved across species, Cdc13 does not resemble its mammalian counterpart CTC1 either in sequence or domain organization, and Cdc13 but not CTC1 displays functions independently of the rest of CST. Whereas the structures of human CTC1 and CST have been determined, the molecular organization of Cdc13 remains poorly understood. Here, we dissect the molecular architecture of Candida glabrata Cdc13 and show how it regulates binding to telomeric sequences. Cdc13 forms dimers through the interaction between OB-fold 2 (OB2) domains. Dimerization stimulates binding of OB3 to telomeric sequences, resulting in the unfolding of ssDNA secondary structure. Once bound to DNA, Cdc13 prevents the refolding of ssDNA by mechanisms involving all domains. OB1 also oligomerizes, inducing higher-order complexes of Cdc13 in vitro. OB1 truncation disrupts these complexes, affects ssDNA unfolding and reduces telomere length in C. glabrata. Together, our results reveal the molecular organization of C. glabrata Cdc13 and how this regulates the binding and the structure of DNA, and suggest that yeast species evolved distinct architectures of Cdc13 that share some common principles.
Multi-layered chromatin proteomics identifies cell vulnerabilities in DNA repair
Authors: Sigismondo Gianluca , Arseni Lavinia , Palacio-Escat Nicolàs , Hofmann Thomas G , Seiffert Martina , Krijgsveld Jeroen 
Published: January 2023

Abstract
The DNA damage response (DDR) is essential to maintain genome stability, and its deregulation predisposes to carcinogenesis while encompassing attractive targets for cancer therapy. Chromatin governs the DDR via the concerted interplay among different layers, including DNA, histone post-translational modifications (hPTMs) and chromatin-associated proteins. Here, we employ multi-layered proteomics to characterize chromatin-mediated functional interactions of repair proteins, signatures of hPTMs and the DNA-bound proteome during DNA double-strand break (DSB) repair at high temporal resolution. Our data illuminate the dynamics of known and novel DDR-associated factors both at chromatin and at DSBs. We functionally attribute novel chromatin-associated proteins to repair by non-homologous end-joining (NHEJ), homologous recombination (HR) and DSB repair pathway choice. We reveal histone reader ATAD2, microtubule organizer TPX2 and histone methyltransferase G9A as regulators of HR and involved in poly-ADP-ribose polymerase-inhibitor sensitivity. Furthermore, we distinguish hPTMs that are globally induced by DNA damage from those specifically acquired at sites flanking DSBs (γH2AX foci-specific) and profiled their dynamics during the DDR. Integration of complementary chromatin layers implicates G9A-mediated monomethylation of H3K56 in DSBs repair via HR. Our data provide a dynamic chromatin-centered view of the DDR that can be further mined to identify novel mechanistic links and cell vulnerabilities in DSB repair.
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

AbstractN 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

Abstract
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

Abstract
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

AbstractReliance 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

AbstractThe 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.

Summary
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.

Summary
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.
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

AbstractAntimicrobial 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.ImportanceCarbapenem-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

AbstractThe 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

AbstractRubisco 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

AbstractNeophobia, 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.