bluuebunny/crossref_metadata_2025 huggingface dataset:
Withdrawn 2.0—update on withdrawn drugs with pharmacovigilance data
Authors: Gallo Kathleen , Goede Andrean , Eckert Oliver-Andreas , Gohlke Bjoern-Oliver , Preissner Robert
Published: November 2023

One challenge in the development of novel drugs is their interaction with potential off-targets, which can cause unintended side-effects, that can lead to the subsequent withdrawal of approved drugs. At the same time, these off-targets may also present a chance for the repositioning of withdrawn drugs for new indications, which are potentially rare or more severe than the original indication and where certain adverse reactions may be avoidable or tolerable. To enable further insights into this topic, we updated our database Withdrawn by adding pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS), as well as mechanism of action and human disease pathway prediction features for drugs that are or were temporarily withdrawn or discontinued in at least one country. As withdrawal data are still spread over dozens of national websites, we are continuously updating our lists of discontinued or withdrawn drugs and related (off-)targets. Furthermore, new systematic entry points for browsing the data, such as an ATC tree, were added, increasing the accessibility of the database in a user-friendly way. Withdrawn 2.0 is publicly available without the need for registration or login at https://bioinformatics.charite.de/withdrawn_3/index.php.
MetaboLights: open data repository for metabolomics
Authors: Yurekten Ozgur , Payne Thomas , Tejera Noemi , Amaladoss Felix Xavier , Martin Callum , Williams Mark , O’Donovan Claire
Published: November 2023

MetaboLights is a global database for metabolomics studies including the raw experimental data and the associated metadata. The database is cross-species and cross-technique and covers metabolite structures and their reference spectra as well as their biological roles and locations where available. MetaboLights is the recommended metabolomics repository for a number of leading journals and ELIXIR, the European infrastructure for life science information. In this article, we describe the continued growth and diversity of submissions and the significant developments in recent years. In particular, we highlight MetaboLights Labs, our new Galaxy Project instance with repository-scale standardized workflows, and how data public on MetaboLights are being reused by the community. Metabolomics resources and data are available under the EMBL-EBI’s Terms of Use at https://www.ebi.ac.uk/metabolights and under Apache 2.0 at https://github.com/EBI-Metabolights.
Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes
Authors: Yoon Peter H , Skopintsev Petr , Shi Honglue , Chen LinXing , Adler Benjamin A , Al-Shimary Muntathar , Craig Rory J , Loi Kenneth J , DeTurk Evan C , Li Zheng , Amerasekera Jasmine , Trinidad Marena , Nisonoff Hunter , Chen Kai , Lahiri Arushi , Boger Ron , Jacobsen Steve , Banfield Jillian F , Doudna Jennifer A
Published: November 2023

RNA-guided endonucleases form the crux of diverse biological processes and technologies, including adaptive immunity, transposition, and genome editing. Some of these enzymes are components of insertion sequences (IS) in the IS200/IS605 and IS607 transposon families. Both IS families encode a TnpA transposase and a TnpB nuclease, an RNA-guided enzyme ancestral to CRISPR-Cas12s. In eukaryotes, TnpB homologs occur as two distinct types, Fanzor1s and Fanzor2s. We analyzed the evolutionary relationships between prokaryotic TnpBs and eukaryotic Fanzors, which revealed that both Fanzor1s and Fanzor2s stem from a single lineage of IS607 TnpBs with unusual active site arrangement. The widespread nature of Fanzors implies that the properties of this particular lineage of IS607 TnpBs were particularly suited to adaptation in eukaryotes. Biochemical analysis of an IS607 TnpB and Fanzor1s revealed common strategies employed by TnpBs and Fanzors to co-evolve with their cognate transposases. Collectively, our results provide a new model of sequential evolution from IS607 TnpBs to Fanzor2s, and Fanzor2s to Fanzor1s that details how genes of prokaryotic origin evolve to give rise to new protein families in eukaryotes.
PRIMPOL ensures robust handoff between on-the-fly and post-replicative DNA lesion bypass
Authors: Mellor Christopher , Nassar Joelle , Šviković Saša , Sale Julian E
Published: November 2023

The primase/polymerase PRIMPOL restarts DNA synthesis when replication is arrested by template impediments. However, we do not have a comprehensive view of how PRIMPOL-dependent repriming integrates with the main pathways of damage tolerance, REV1-dependent ‘on-the-fly’ lesion bypass at the fork and PCNA ubiquitination-dependent post-replicative gap filling. Guided by genome-wide CRISPR/Cas9 screens to survey the genetic interactions of PRIMPOL in a non-transformed and p53-proficient human cell line, we find that PRIMPOL is needed for cell survival following loss of the Y-family polymerases REV1 and POLη in a lesion-dependent manner, while it plays a broader role in promoting survival of cells lacking PCNA K164-dependent post-replicative gap filling. Thus, while REV1- and PCNA K164R-bypass provide two layers of protection to ensure effective damage tolerance, PRIMPOL is required to maximise the effectiveness of the interaction between them. We propose this is through the restriction of post-replicative gap length provided by PRIMPOL-dependent repriming.
Structural and biochemical analysis of the PARP1-homology region of PARP4/vault PARP
Authors: Frigon Léonie , Pascal John M
Published: November 2023

PARP4 is an ADP-ribosyltransferase that resides within the vault ribonucleoprotein organelle. Our knowledge of PARP4 structure and biochemistry is limited relative to other PARPs. PARP4 shares a region of homology with PARP1, an ADP-ribosyltransferase that produces poly(ADP-ribose) from NAD+ in response to binding DNA breaks. The PARP1-homology region of PARP4 includes a BRCT fold, a WGR domain, and the catalytic (CAT) domain. Here, we have determined X-ray structures of the PARP4 catalytic domain and performed biochemical analysis that together indicate an active site that is open to NAD+ interaction, in contrast to the closed conformation of the PARP1 catalytic domain that blocks access to substrate NAD+. We have also determined crystal structures of the minimal ADP-ribosyltransferase fold of PARP4 that illustrate active site alterations that restrict PARP4 to mono(ADP-ribose) rather than poly(ADP-ribose) modifications. We demonstrate that PARP4 interacts with vault RNA, and that the BRCT is primarily responsible for the interaction. However, the interaction does not lead to stimulation of mono(ADP-ribosylation) activity. The BRCT–WGR–CAT of PARP4 has lower activity than the CAT alone, suggesting that the BRCT and WGR domains regulate catalytic output. Our study provides first insights into PARP4 structure and regulation and expands understanding of PARP structural biochemistry.
Structural and biochemical insights into NEIL2’s preference for abasic sites
Authors: Eckenroth Brian E , Bumgarner Joshua D , Matsumoto-Elliott Olivia , David Sheila S , Doublié Sylvie
Published: November 2023

Cellular DNA is subject to damage from a multitude of sources and repair or bypass of sites of damage utilize an array of context or cell cycle dependent systems. The recognition and removal of oxidatively damaged bases is the task of DNA glycosylases from the base excision repair pathway utilizing two structural families that excise base lesions in a wide range of DNA contexts including duplex, single-stranded and bubble structures arising during transcription. The mammalian NEIL2 glycosylase of the Fpg/Nei family excises lesions from each of these DNA contexts favoring the latter two with a preference for oxidized cytosine products and abasic sites. We have determined the first liganded crystal structure of mammalian NEIL2 in complex with an abasic site analog containing DNA duplex at 2.08 Å resolution. Comparison to the unliganded structure revealed a large interdomain conformational shift upon binding the DNA substrate accompanied by local conformational changes in the C-terminal domain zinc finger and N-terminal domain void-filling loop necessary to position the enzyme on the DNA. The detailed biochemical analysis of NEIL2 with an array of oxidized base lesions indicates a significant preference for its lyase activity likely to be paramount when interpreting the biological consequences of variants.
Accumulation of Phosphorylated SnRK2 Substrate 1 Promotes Drought Escape in Arabidopsis
Authors: Katagiri Sotaro , Kamiyama Yoshiaki , Yamashita Kota , Iizumi Sara , Suzuki Risa , Aoi Yuki , Takahashi Fuminori , Kasahara Hiroyuki , Kinoshita Toshinori , Umezawa Taishi
Published: November 2023

Plants adopt optimal tolerance strategies depending on the intensity and duration of stress. Retaining water is a priority under short-term drought conditions, whereas maintaining growth and reproduction processes takes precedence over survival under conditions of prolonged drought. However, the mechanism underlying changes in the stress response depending on the degree of drought is unclear. Here, we report that SNF1-related protein kinase 2 (SnRK2) substrate 1 (SNS1) is involved in this growth regulation under conditions of drought stress. SNS1 is phosphorylated and stabilized by SnRK2 protein kinases reflecting drought conditions. It contributes to the maintenance of growth and promotion of flowering as drought escape by repressing stress-responsive genes and inducing FLOWERING LOCUS T (FT) expression, respectively. SNS1 interacts with the histone methylation reader proteins MORF-related gene 1 (MRG1) and MRG2, and the SNS1–MRG1/2 module cooperatively regulates abscisic acid response. Taken together, these observations suggest that the phosphorylation and accumulation of SNS1 in plants reflect the intensity and duration of stress and can serve as a molecular scale for maintaining growth and adopting optimal drought tolerance strategies under stress conditions.
Artificial intelligence and allergic rhinitis: does ChatGPT increase or impair the knowledge?
Authors: Høj Simon , Thomsen Simon F , Meteran Hanieh , Sigsgaard Torben , Meteran Howraman
Published: November 2023

Background

Optimal management of allergic rhinitis requires patient education with easy access to accurate information. However, previous online platforms have provided misleading information. The demand for online medical information continues to grow, especially with the introduction of advanced chatbots like ChatGPT.

Methods

This study aimed to evaluate the quality of information provided by ChatGPT regarding allergic rhinitis. A Likert scale was used to assess the accuracy of responses, ranging from 1 to 5. Four authors independently rated the responses from a healthcare professional’s perspective.

Results

A total of 20 questions covering various aspects of allergic rhinitis were asked. Among the answers, eight received a score of 5 (no inaccuracies), five received a score of 4 (minor non-harmful inaccuracies), six received a score of 3 (potentially misinterpretable inaccuracies) and one answer had a score of 2 (minor potentially harmful inaccuracies).

Conclusions

The variability in accuracy scores highlights the need for caution when relying solely on chatbots like ChatGPT for medical advice. Patients should consult qualified healthcare professionals and use online sources as a supplement. While ChatGPT has advantages in medical information delivery, its use should be approached with caution. ChatGPT can be useful for patient education but cannot replace healthcare professionals.
Parental Schooling, Educational Attainment, Skills, and Earnings: A Trend Analysis across Fifteen Countries
Authors: Pensiero Nicola , Barone Carlo
Published: November 2023

Using data on fifteen countries based on the harmonization of IALS and PIAC data, we provide a cross-national analysis of the evolution of the role of educational attainment and cognitive skills as mediators of intergenerational inequalities between 1994 and 2015. We find that the association between parents’ education and children’s earnings is large and highly stable over time in most countries, except for Scandinavian countries, where we detect a downward trend. Conversely, the United States stands out as the country displaying the largest earning differentials by parents’ education and as the only country where these differentials increased over time. We demonstrate that educational attainment and skills contributed in different ways to the persistence of these intergenerational inequalities. On the one hand, educational equalization was compensated by increasing earning returns to education in several countries. On the other hand, the association between parents’ education and cognitive skills, as well as the related earning returns, stayed largely unchanged across these two decades.
GPS-based noise mapping of Ahmedabad city
Authors: Vora Akshay Vinaychandra , Vasani Rupesh P
Published: November 2023

Noise mapping is an effective tool to measure noise. By noise mapping one can represent noise graphically. Noise mapping was carried out for Ahmedabad city. Data was collected at 633 different locations across the city. Latitude, longitude and real-time noise levels were noted at each location. ArcGIS software was used for creating noise maps and colour noise maps. The percentage of the city covered by the respective value of contour of noise was also found using the software, as well as the number of people in the city suffering from the respective levels of noise. Considering all the results, a multi-linear regression model was developed to predict noise, using SPSS statistics software. The developed model was analysed using an R2 test as well as a paired t-test.
Influence of Preharvest Polyoxin-D Applications with or Without Spray Oils on Brown Rot Development and Tree Health of Peach
Authors: Gura William P. , Gelain Jhulia , Schnabel Guido
Published: November 2023

Polyoxin-D is a microbial fermentation product registered to control multiple crop diseases. However, there is limited knowledge of the effect of polyoxin-D against peach brown rot or potential efficacy improvements through combinations with essential or mineral oils. In this study, we evaluated the efficacy of polyoxin-D with or without thyme oil or mineral oil to control brown rot on peach caused by Monilinia fructicola in a multiyear study. Treatments were applied preharvest and included OSO 5% (polyoxin-D), OSO 5% + ThymeGuard 0.25% (polyoxin-D + thyme oil), and OSO 5% + PureSpray Green 0.5% (polyoxin-D + mineral oil). Assessment of preharvest brown rot revealed that the OSO 5% treatment had less disease incidence (9.4% on average) compared with the untreated control (20.0% on average), but no significant differences were found between OSO 5% + PureSpray Green (11.8% on average) and OSO 5% + ThymeGuard (11.4% on average). All three OSO 5% treatments reduced postharvest brown rot compared with the untreated control, but there were no significant differences in disease incidence between experimental treatments. Phytotoxicity was observed in the form of premature leaf drop. The greatest leaf drop was recorded for OSO 5% + PureSpray Green with 36.5% blind nodes on average. In summary, polyoxin-D (OSO 5%), when applied by handgun to runoff using 1,870 liters/ha water volume, significantly reduced preharvest and postharvest brown rot disease but caused some premature leaf drop. The addition of thyme oil or mineral oil did not improve its efficacy.
An Analysis of Negative One-star Patient Reviews and Complaints for Pediatric Orthopaedic Surgeons throughout the United States: A Retrospective Study
Authors: Hitchman Kyle J. , Baumann Anthony N. , Glasgow Wyatt R. , Rivera Karla G. , Anastasio Albert T. , Walley Kempland C. , Baldwin Keith D.
Published: November 2023

Objective:

Patients commonly use physician review websites when choosing a surgeon for an elective procedure. Although data exist regarding other orthopaedic specialties, no study has investigated one-star reviews for pediatric orthopaedic surgeons. The goal of this retrospective study was to classify the factors contributing to one-star reviews of pediatric orthopaedic surgeons to identify which areas contribute to lower patient satisfaction.

Methods:

Patient ratings on a 5-star system and comments about pediatric orthopaedic surgeons were collected from the state with the most physicians registered in the “Pediatric Orthopaedic Society of North American” database for each of the 9 geographical regions of the United States as defined by the Association of American Medical Colleges. One-star reviews that included comments were classified as either surgical or nonsurgical. These comments were then further classified based on their content.

Results:

Three hundred fifty-four one-star reviews with 700 complaints were included in this study. Of these complaints, 481 (68.7%) were from nonsurgical patients and 219 (31.3%) were from surgical patients. Nonsurgical patients were significantly more likely to reference the amount of time spent with the physician (12.9% to 6.6%, P = 0.026), wait time (11.9% to 0.0%, P < 0.001), and bedside manner (41.2% to 22.8%, P < 0.001). Patients who said they had undergone a surgical procedure in their one-star review were significantly more likely to reference a disagreement with the physician’s decision or plan (35.3% to 17.5%, P < 0.001), and uncontrolled pain (21.6% to 5.2%, P < 0.001). There was no significant difference in the comments that referenced medical staff or institutional complaints between surgical and nonsurgical patients (13.8% to 11.4%, P = 0.424).

Conclusion:

Most one-star reviews of pediatric orthopaedic surgeons referenced interpersonal skills and other nonclinical aspects of a clinical encounter, with bedside manner being the most frequent complaint. Patients who had undergone surgical procedures were less likely to leave a one-star review, but if they did, their comment was usually about a disagreement with the physician’s plan.

Clinical Relevance:

Prognostic studies III.
The Surgical Algorithm for the AO Spine Sacral Injury Classification System
Authors: Lee Yunsoo , Lambrechts Mark , Narayanan Rajkishen , Bransford Richard , Benneker Lorin , Schnake Klaus , Öner Cumhur , Canseco Jose A. , Kepler Christopher K. , Schroeder Gregory D. , Vaccaro Alexander R. ,   AO Spine Sacral Classification Group Members
Published: November 2023

Study Design:

Global cross-sectional survey.

Objective:

To establish a surgical algorithm for sacral fractures based on the AO Spine Sacral Injury Classification System.

Summary of Background Data:

Although the AO Spine Sacral Injury Classification has been validated across an international audience of surgeons, a consensus on a surgical algorithm has yet to be developed for sacral fractures by using the Sacral AO Spine Injury Score (Sacral AOSIS).

Methods:

A survey was sent to general orthopedic surgeons, orthopedic spine surgeons, and neurosurgeons across the five AO Spine regions of the world. Descriptions of controversial sacral injuries based on different fracture subtypes were given and surgeons were asked whether the patient should undergo operative or non-operative management. The results of the survey were used to create a surgical algorithm based on each subtypes’ Sacral AOSIS.

Results:

International agreement of 70% was decided on by the AO Spine Knowledge Forum Trauma experts to indicate a recommendation of initial operative intervention. Using this, sacral fracture subtypes of AOSIS 5 or greater were considered operative while those with AOSIS 4 or less were generally non-operative. For subtypes with an AOSIS of 3 or 4, if the sacral fracture was associated with an anterior pelvic ring injury (M3 case-specific modifier), intervention should be left to the surgeons’ discretion.

Conclusion:

The AO Spine Sacral Injury Classification System offers a validated hierarchical system to approach sacral injuries. Through multi-specialty and global surgeon input, a surgical algorithm was developed to determine appropriate operative indications for sacral trauma. Further validation is required, but this algorithm provides surgeons across the world with the basis for discussion and the development of standard of care treatment.

Level of Evidence:

Level IV.
Technique for Minimally Invasive, Arthroscopic-assisted Distal Radius Fracture Fixation
Authors: Lau Vincent , Tosti Rick , Rivlin Michael
Published: November 2023

Distal radius fractures are common injuries that often require surgical intervention. Commonly, these fractures are fixed using open reduction internal fixation with plating and screws. This often requires a more extensive soft tissue dissection and exposure. In contrast for certain cases, percutaneous headless compression screws may be appropriate. We present a technique for minimally invasive arthroscopic-assisted reduction and percutaneous screw fixation with an extremity traction device. A case is provided to demonstrate the technique as a viable option for the treatment of intra-articular distal radius fractures.
Cancer cachexia: Focus on cachexia factors and inter-organ communication
Authors: Wang Yongfei , Dong Zikai , An Ziyi , Jin Weilin
Published: November 2023

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs, which is mediated by cancer cachexia factors. Cancer cachexia factors, being the general name of inflammatory factors, circulating proteins, metabolites, and microRNA secreted by tumor or host cells, play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia. Cancer cachexia factors are also a potential target for the diagnosis and treatment. The pathogenesis of cachexia is unclear and no clear effective treatment is available. Thus, the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed. From the point of signal communication between organs mediated by cancer cachexia factors, finding a deeper understanding of the pathogenesis, diagnosis, and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment. This review begins with cancer cachexia factors released during the interaction between tumor and host cells, and provides a comprehensive summary of the pathogenesis, diagnosis, and treatment for cancer cachexia, along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors. This summary aims to deepen medical community's understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.
Diagnosis and management of blunt cardiac injury: What you need to know
Authors: Biffl Walter L. , Fawley Jason A. , Mohan Rajeev C.
Published: November 2023

Blunt cardiac injury (BCI) encompasses a wide spectrum, from occult and inconsequential contusion to rapidly fatal cardiac rupture. A small percentage of patients present with abnormal electrocardiogram or shock, but most are initially asymptomatic. The potential for sudden dysrhythmia or cardiac pump failure mandates consideration of the presence of BCI, including appropriate monitoring and management. In this review, we will present what you need to know to diagnose and manage BCI.
Williamsia muralis bacteremia in a patient with Fanconi anemia after hematopoietic cell transplantation
Authors: Sonoda Motoshi , Motomura Yoshitomo , Ishimura Masataka , Kanno Shunsuke , Kiyosuke Makiko , Ohga Shouichi
Published: November 2023

Williamsia muralis is an environmental bacterium first detected in 1999. The isolated infection with W. muralis has been reported in two elderly patients that have been associated with the surgical intervention of artificial objects. We present a case of bacteremia caused by W. muralis following hematopoietic cell transplantation (HCT).
Case presentation:
A 10-year-old Japanese boy presented with fever and the left cheek swelling 8 days after HCT for the treatment of Fanconi anemia. Gram-positive, rod-shaped bacteria were isolated from the blood cultures after five days incubation. The 16S ribosomal RNA sequencing but not mass spectrometry identified the strain of W. muralis (1,414 bp, %ID: 100%). The phlegmon did not respond to antimicrobial therapy but remitted with defervescence after a successful engraftment with teicoplanin and meropenem therapy on day 16 after HCT. The patient experienced the recurrence of bacteremia, leading to central venous catheter (CVC) line removal. The same strain of W. muralis was isolated from the cultured tip of the CVC. The first case of W. muralis bacteremia and was complicated by CVC infection after HCT.
Conclusion:
W. muralis bacteremia developed in an immunocompromised child. Introduction of artificial objects into the body raises a risk of rare infection with the slowly growing environmental bacteria.
Phylotaxonomic assessment based on four core gene sets and proposal of a genus definition among the families Paracoccaceae and Roseobacteraceae
Authors: Zhang Dao-Feng , He Wei , Shao Zongze , Ahmed Iftikhar , Zhang Yuqin , Li Wen-Jun , Zhao Zhe
Published: November 2023

The families Paracoccaceae and

Roseobacteraceae

comprise metabolically, phenotypically and genotypically diverse members, and their descriptions rely heavily on 16S rRNA gene analysis. Hundreds of genera have been reported within the two families and misclassifications have been a reoccurring problem, even when the taxonomies have been established based on genome-scale phylogenetic reconstructions. In this study, we conducted a comprehensive phylotaxonomic assessment of the families Paracoccaceae and

Roseobacteraceae

based on four ubiquitous gene sets, bac120 (120 genes in Bacteria), rhodo268 (268 genes in ‘

Rhodobacteraceae

’, defined in this study), rp1 (16 ribosomal protein genes in Prokaryote) and rp2 (23 ribosomal protein genes in Prokaryote), using two tree-inferring applications and two approaches (supermatrix and consensus). The results suggested that the four supermatrix trees based on bac120 and rhodo268 shared a high proportion of common nodes (>88.4 %) and the topology was reproducible among all the trees within most of the genera. The evolutionary distance (ED) analysis showed significant overlapping between the intergeneric and intrageneric comparisons, implying that the proposal of some genera seemed to be unnecessary. In addition, the bac120 gene set and the FastTree program were found to be the most cost-effective way to conduct phylogenomic analysis of the families Paracoccaceae and

Roseobacteraceae

. An ED threshold of 0.21–0.23 based on either bac120 or rhodo268 was proposed as one standard for later genus delimitation in these families. A comprehensive phylogenetic framework is presented in this study and the proposed genus definition will help to establish a more reasonable taxonomy in the families Paracoccaceae and

Roseobacteraceae

.
Parallel loss of type VI secretion systems in two multi-drug-resistant Escherichia coli lineages
Authors: Cummins Elizabeth A. , Moran Robert A. , Snaith Ann E. , Hall Rebecca J. , Connor Christopher H. , Dunn Steven J. , McNally Alan
Published: November 2023

The repeated emergence of multi-drug-resistant (MDR)

Escherichia coli

clones is a threat to public health globally. In recent work, drug-resistant

E. coli

were shown to be capable of displacing commensal

E. coli

in the human gut. Given the rapid colonization observed in travel studies, it is possible that the presence of a type VI secretion system (T6SS) may be responsible for the rapid competitive advantage of drug-resistant

E. coli

clones. We employed large-scale genomic approaches to investigate this hypothesis. First, we searched for T6SS genes across a curated dataset of over 20 000 genomes representing the full phylogenetic diversity of

E. coli

. This revealed large, non-phylogenetic variation in the presence of T6SS genes. No association was found between T6SS gene carriage and MDR lineages. However, multiple clades containing MDR clones have lost essential structural T6SS genes. We characterized the T6SS loci of ST410 and ST131 and identified specific recombination and insertion events responsible for the parallel loss of essential T6SS genes in two MDR clones.
Identification of a morphogene required for tapered filament termini in filamentous cyanobacteria
Authors: Parrett Gabriel A. , Brones Peyton D. , Jenkins Garrett M. , Mounts Savanna M. , Nguyen Alicia , Risser Douglas D.
Published: November 2023

Although the photosynthetic cyanobacteria are monophyletic, they exhibit substantial morphological diversity across species, and even within an individual species due to phenotypic plasticity in response to life cycles and environmental signals. This is particularly prominent among the multicellular filamentous cyanobacteria. One example of this is the appearance of tapering at the filament termini. However, the morphogenes controlling this phenotype and the adaptive function of this morphology are not well defined. Here, using the model filamentous cyanobacterium

Nostoc punctiforme

ATCC29133 (PCC73102), we identify tftA, a morphogene required for the development of tapered filament termini. The tftA gene is specifically expressed in developing hormogonia, motile trichomes where the tapered filament morphology is observed, and encodes a protein containing putative amidase_3 and glucosaminidase domains, implying a function in peptidoglycan hydrolysis. Deletion of tftA abolished filament tapering inidcating that TftA plays a role in remodelling the cell wall to produce tapered filaments. Genomic conservation of tftA specifically in filamentous cyanobacteria indicates this is likely to be a conserved mechanism among these organisms. Finally, motility assays indicate that filaments with tapered termini migrate more efficiently through dense substratum, providing a plausible biological role for this morphology.
Non-REM parasomnia experiences share EEG correlates with dreams
Authors: Cataldi Jacinthe , Stephan Aurélie M. , Haba-Rubio José , Siclari Francesca
Published: November 2023

Sleepwalking and related parasomnias result from sudden and incomplete awakenings out of slow wave sleep. Clinical observations suggest that behavioral episodes can occur without consciousness and recollection, or in relation to dream-like experiences. To understand what accounts for these differences in consciousness and amnesia, we recorded parasomnia episodes with high-density EEG and interviewed participants immediately afterwards. Compared to reports of unconsciousness (19%), reports of conscious experience (81%) were preceded, during prior sleep, by high-amplitude slow waves in anterior cortical regions and an activation of posterior cortical regions. Reduced posterior slow wave activity was also present during the episode when patients displayed elaborate behaviours in relation to dream-like scenarios. Amnesia for the experience (25%) was modulated by right medial temporal activation during prior sleep and fronto-parietal slow wave activity during the episode. Thus, the neural correlates of parasomnia experiences are similar to those previously reported for dreams and therefore likely reflect core physiological processes involved in sleep consciousness.
Temperature effects on the global patterns of photosynthetic quantum efficiency
Authors: Sandoval David , Flo Victor , Morfopoulos Catherine , Prentice Iain Colin
Published: November 2023

The photosynthetic quantum efficiency (φ0) is a key input parameter for modelling gross primary productivity in terrestrial biosphere models. Historically, these models assumedφ0to be constant, based on leaf measurements under unstressed conditions and within a narrow temperature range. However, increasing evidence suggests a temperature-dependentφ0on temperature, though it remains unclear whether this response is generalized or if it propagates to the ecosystem. Here, we derivedφ0(T) at the ecosystem level for sites distributed globally, using sub-daily eddy covariance measurements of CO2exchange and above/below-canopy measurements of photosynthetic flux density to derive the fraction of absorbed photosynthetically active radiation (fAPAR). We found thatφ0(T) shows a consistent bell-shaped response curve with temperature in all the sites we analysed. These patterns held when analysed with a larger global dataset using remotely sensed fAPAR. Furthermore, we observed that the values ofφ0(T) are not markedly different among biomes, instead, there is a gradual transition of the peakφ0(T) which decreases following an aridity gradient. Additionally, we noted varying sensitivity to temperature among the different sites, with sensitivity increasing as growth temperature decreases.
Operator model for evolutionary dynamics
Authors: Park Kangbien , Bae Yonghee
Published: November 2023

Drift, selection, and mutation are integral evolutionary factors. In this article,operator modelis newly suggested to intuitively represent those evolutionary factors into mathematical operators, and to ultimately offer unconventional methodology for understanding evolutionary dynamics. To be specific, each of the drift, selection, and mutation was respectively interpreted as operator which in essence is a random matrix that acts upon the vector which contains population distribution information. The simulation results from the operator model coincided with the previous theoretical results for beneficial mutation accumulation rate in concurrent and successional regimes for asexually reproducing case. Furthermore, beneficial mutation accumulation in strong drift regime for asexually reproducing case was observed from the simulation while allowing the interactions of mutations with diverse selection coefficients. Lastly, methods to justify, reinforce, apply, and expand the operator model were discussed to scrutinize the implications of the model. With its unique characteristics, the operator model is expected to broaden perspective and to offer effective methodology for understanding the evolutionary process.
Continent-wide genomic analysis of the African buffalo (Syncerus caffer)
Authors: Talenti Andrea , Wilkinson Toby , Cook Elizabeth A. , Hemmink Johanneke D. , Paxton Edith , Mutinda Matthew , Ngulu Stephen D. , Jayaraman Siddharth , Bishop Richard P. , Obara Isaiah , Hourlier Thibaut , Giron Carlos Garcia , Martin Fergal J. , Labuschagne Michel , Atimnedi Patrick , Nanteza Anne , Keyyu Julius D. , Mramba Furaha , Caron Alexandre , Cornelis Daniel , Chardonnet Philippe , Fyumagwa Robert , Lembo Tiziana , Auty Harriet K. , Michaux Johan , Smitz Nathalie , Toye Philip , Robert Christelle , Prendergast James G.D. , Morrison Liam J.
Published: November 2023

The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest qualityde novogenome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided surprisingly little support for the currently described four subspecies, but indicated three main lineages, in Western/Central, Eastern and Southern Africa, respectively. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.
DONOR VARIABILITY IN HUMAN MESENCHYMAL STEM CELL OSTEOGENIC RESPONSE AS A FUNCTION OF PASSAGE CONDITIONS AND DONOR SEX
Authors: Kolliopoulos Vasiliki , Tiffany Aleczandria , Polanek Maxwell , Harley Brendan A.C.
Published: November 2023

Contemporary tissue engineering efforts often seek to use mesenchymal stem cells (MSCs) due to their potential to differentiate to various tissue-specific cells and generate a pro-regenerative secretome. While MSC differentiation and therapeutic potential can differ as a function of matrix environment, it may also be widely influenced as a function of donor-to-donor variability. Further, effects of passage number and donor sex may further convolute the identification of clinically effective MSC-mediated regeneration technologies. We report efforts to adapt a well-defined mineralized collagen scaffold platform to study the influence of MSC proliferation and osteogenic potential as a function of passage number and donor sex. Mineralized collagen scaffolds broadly support MSC osteogenic differentiation and regenerative potency in the absence of traditional osteogenic supplements for a wide range of MSCs (rabbit, rat, porcine, human). We obtained a library of bone marrow and adipose tissue derived stem cells to examine donor-variability of regenerative potency in mineralized collagen scaffolds. MSCs displayed reduced proliferative capacity as a function of passage duration. Further, MSCs showed significant sex-based differences. Notably, MSCs from male donors displayed significantly higher metabolic activity and proliferation while MSCs from female donor displayed significantly higher osteogenic response via increased alkaline phosphate activity, osteoprotegerin release, and mineral formation in vitro. Our study highlights the essentiality of considering MSC donor sex and culture expansion in future studies of biomaterial regenerative potential.
Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth
Authors: Hernández Luis Cruz , Montero María Teresa Sánchez , Rivera-Ramos Alberto , García-Revilla Juan , Talaverón Rocío , Mulero-Acevedo Marta , Venero José Luis , Soto Manuel Sarmiento
Published: November 2023

The glycoprotein Galectin-3 (Gal-3) is a multifunctional molecule that plays a pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although the involvement of Gal-3 in tumour progression, resistance to treatment and immunosuppression has long been studied in different cancer types, mainly outside the central nervous system, its elevated expression in myeloid and glial cells underscores its profound impact on the brain’s immune response. In this context, microglia and infiltrating macrophages, the predominant non-cancerous cells within the tumour microenvironment, assume critical roles in establishing an immunosuppressive milieu in diverse brain tumours. Through the utilisation of primary cell cultures and immortalised microglial cell lines, we have elucidated the central role of Gal-3 in promoting cancer cell migration, invasion, and an immunosuppressive microglial phenotypic activation. Furthermore, employing two distinct in vivo models encompassing primary (glioblastoma) and secondary brain tumours (breast cancer brain metastasis), our histological and transcriptomic analysis show that Gal-3 depletion triggers a robust pro-inflammatory response within the tumour microenvironment, notably based on interferon-related pathways. Interestingly, this response is prominently observed in tumour-associated microglia and macrophages (TAMs), resulting in the suppression of cancer cells growth.
Theta activity discriminates high-level, species-specific body processes
Authors: Chesley Jane , Riecke Lars , Lu Juanzhi , Vogels Rufin , de Gelder Beatrice
Published: November 2023

Among social stimuli that trigger rapid reactions, body images occupy a prominent place. Given that bodies carry information about other agents’ intentions, actions and emotional expressions, a foundational question concerns the neural basis of body processing. Previous fMRI studies have investigated this but were not yet able to clarify the time course and its functional significance. The present EEG study investigated the role of slow oscillatory cortical activity in body processing and species-specificity. Human participants viewed naturalistic images of human and monkey bodies, faces, and objects, along with mosaic-scrambled versions to control for low-level visual features. Analysis of event-related theta power (4 – 7 Hz) combined with data-driven methods revealed a strong, body-evoked neural response that is specific to human bodies and likely originates from a widespread cortical region during a time window of 150 – 550 ms after the onset of the body image. Our results corroborate recent research proposing a widespread, species-specific cortical network of human body processing. We submit that this network may play an essential role in linking body processes to movement intentions.
Frontal oscillatory beta bursts have rhythmically distinct regimes with differing functional relevance
Authors: Langford Zachary D , Procyk Emmanuel , Wilson Charles R E
Published: November 2023

The importance of studying the transient burst-like nature of beta- and gamma-band oscillations has become increasingly clear. This approach challenges accepted interpretations of oscillatory behavior and emphasizes the importance of examining phenomena at appropriate temporal scales, as opposed to trial averages. Diversity in the detailed temporal form of these real-time phenomena has been under-considered, yet it should provide important information about function. Here we studied such bursts at beta frequencies, and explicitly distinguished transient bursts characterized by high power (BoP) and those marked by consistent cycles (BoC) using methods tailored to capture each characteristic. Analysis of neural recordings from mice and macaques revealed two distinct and largely independent beta burst categories within the same temporal content. BoP bursts were true transients featuring a substantial amplitude peak and minimal rhythmicity, while BoC bursts were much more rhythmic, seemingly meeting a more classic definition of an oscillation. Importantly, these two classes of beta burst showed differing functional relevance within the same signal. In a search-repeat task, BoC bursts occurred more often in the search phase, whereas BoP bursts dominated the repeat phase. As such, beta frequency neural signals encompass at least two transient phenomena, each with potentially distinct functional roles.
Bacterial community characterization by deep learning aided image analysis in soil chips
Authors: Zou Hanbang , Sopasakis Alexandros , Maillard François , Karlsson Erik , Duljas Julia , Silwer Simon , Ohlsson Pelle , Hammer Edith C.
Published: November 2023

Soil microbes play an important role in governing global processes such as carbon cycling, but it is challenging to study them embedded in their natural environment and at the single cell level due to the opaque nature of the soil. Nonetheless, progress has been achieved in recent years towards visualizing microbial activities and organo-mineral interaction at the pore scale, especially thanks to the development of microfluidic ‘soil chips’ creating transparent soil model habitats. Image-based analyses come with new challenges as manual counting of bacteria in thousands of digital images taken from the soil chips is excessively time-consuming, while simple thresholding cannot be applied due to the background of soil minerals and debris. Here, we adopt the well-developed deep learning algorithm Mask-RCNN to quantitatively analyse the bacterial communities in soil samples from different locations in the world. This work demonstrates analysis of bacterial abundance from three contrasting locations (Greenland, Sweden and Kenya) using deep learning in microfluidic soil chips in order to characterize population and community dynamics. We additionally quantified cell- and colony morphology including cell size, shape and the cell aggregation level via calculation of the distance to the nearest neighbor. This approach allows for the first time an automated visual investigation of soil bacterial communities, and a crude biodiversity measure based on phenotypic cell morphology, which could become a valuable complement to molecular studies.
Age-Related Differences in Affective Behaviors in Mice: Possible Role of Prefrontal Cortical-Hippocampal Functional Connectivity and Metabolomic Profiles
Authors: Febo Marcelo , Mahar Rohit , Rodriguez Nicholas A. , Buraima Joy , Pompilus Marjory , Pinto Aeja M. , Grudny Matteo M. , Bruijnzeel Adriaan W. , Merritt Matthew E.
Published: November 2023

The differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants further investigation. We assessed age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Prefrontal cortical and hippocampal tissues were excised for metabolomics. Our results indicate that young and old mice differ significantly in affective behavioral, functional connectome and prefrontal cortical-hippocampal metabolome. Young mice show a greater responsivity to novel environmental and social stimuli compared to older mice. Conversely, late middle-aged mice (60wo group) display variable patterns of fear conditioning and with re-testing with a modified context. Functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes was stronger in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups. The results support differential expression of ‘emotionality’ across distinct stages of the mouse lifespan involving greater prefrontal-hippocampal connectivity and neurochemistry.
Darwin’s “neuters” and the evolution of the sex continuum in a superorganism
Authors: Oettler J , Wallner T , Dofka B , Heinze J , Eichner N , Meister G , Errbii M , Rehli M , Gebhard C , Schultner E
Published: November 2023

Ant castes are an amazing example of phenotypic plasticity. In worker-destined embryos of the antCardiocondyla obscurior, the default female developmental trajectory is interrupted even before the gonadal precursor cells acquire a sexual identity. miRNA and mRNA expression in embryos reveal three distinct phenotypic entities: males, females, and “neuters”, as Darwin coined the worker caste in “On the Origin of Species”. Based on these results we propose that haplodiploidy, in conjunction with insect sex determination, allows for the expression of a third dimension on the sex continuum, thus facilitating the evolution of individuals which develop traits their parents do not have.

One sentence summary

Sex and caste differentiation begin during the same embryonic developmental window in the antCardiocondyla obscurior.