bluuebunny/crossref_metadata_2025 huggingface dataset:
Shared decision-making interventions in the choice of antipsychotic prescription in people living with psychosis (SHAPE): protocol for a realist review
Authors: Fitzgerald Ita , Sahm Laura J. , Howe Jo , Maidment Ian , Wallace Emma , Crowley Erin K.
Published: April 2024

Background

Shared decision-making (SDM) has yet to be successfully adopted into routine use in psychiatric settings amongst people living with severe mental illnesses. Suboptimal rates of SDM are particularly prominent amongst patients with psychotic illnesses during antipsychotic treatment choices. Many interventions have been assessed for their efficacy in improving SDM within this context, although results have been variable and inconsistent.

Aims

To generate an in-depth understanding of how, why, for whom, and to what extent interventions facilitating the application of SDM during choice of antipsychotic drug treatment work and the impact of contextual factors on intervention effectiveness.

Methods

This review will use realist review methodology to provide a causal understanding of how and why interventions work when implementing SDM during choice of antipsychotic treatment. The review will take place over five stages; (1) Locating existing theories, (2) Searching for evidence, (3) Selecting articles, (4) Extracting and organising data and (5) Synthesizing evidence and drawing conclusions. An understanding of how and why interventions work will be achieved by developing realist programme theories on intervention effectiveness through iterative literature reviews and engaging with various stakeholder groups, including patient, clinician and carer representatives.

Discussion

This is the first realist review aiming to identify generative mechanisms explaining how and why successful interventions aimed at improving SDM within the parameters outlined work and in which contexts desired outcomes are most likely to be achieved. Review findings will include suggestions for clinicians, policy and decision-makers about the most promising interventions to pursue and their ideal attributes.
Early pregnancy in schools: a socio-ecological analysis of the determinants among teenage girls in Koudougou, Burkina Faso
Authors: Ramde Wendkoaghenda Sophie , Ngangue Patrice , Appolinaire Tonye Kollo , Ly Birama Apho , Bonane Thieba Blandine
Published: April 2024

Introduction

Early pregnancy among adolescents in school has several consequences on the adolescent herself, her family, the whole community, and the child-to-be. This article explores the factors determining early pregnancy among 15-19-year-old secondary school students in Koudougou in Burkina Faso.

Methods

A descriptive and exploratory qualitative study was conducted through focus groups with adolescents and youth in schools and individual interviews with parents, teachers, health workers, and community leaders. The socio-ecological model guided all stages of the study. A thematic analysis of the recorded and transcribed data was conducted using Nvivo 12 software.

Results

A lack of knowledge and information and wrong perceptions about sexuality at the individual level; peer pressure and poverty at the interpersonal level; lack of awareness among teachers and students and health workers’ attitudes at the organizational level; the influence of new information technologies or the media and parents’ irresponsibility at the community level; and the insufficient of sexual and reproductive health services for adolescents as well as the lack of sanctions and law against early pregnancy at the political level were found as enablers. Barriers were the use of contraceptive methods and sexual abstinence; parents-children communication; teachers’ training on sexual sensitization, the creation of youth centers on school campuses and the introduction of sexual education courses; education through media and religion; willingness to introduce sexual education courses in school curricula and legal sanctioning of dealing and consuming drugs in schools.

Conclusion

The study highlighted that the problem of early pregnancy in schools can be solved by acting on the determinants at all levels of the socioecological model by implementing preventive strategies.
Can social media serve as a potential citizen science source for bird-window collision (BWC) data? A study using a decadal data set in Taiwan
Authors: Hsieh Chi-Heng , Hsu Gen-Chang , Wang Ling-Min
Published: April 2024

Citizen science is increasingly used in bird-window collision (BWC) research to collect data. However, few studies have collected BWC data from social media, and it remains unknown whether the data quality is comparable to that of reported on dedicated platforms. To evaluate the potential of social media as a citizen science data source for BWC, we collected BWC data on social media Facebook as well as Taiwan Roadkill Observation Network (TaiRON), the main dedicated citizen science platform for reporting wildlife mortalities in Taiwan. We compared a decade of BWC data (2012–2022) from the two platforms by examining the nationwide geographical coverage and the species compositions of the BWC observations. Overall, we recorded 2,583 BWC cases involving 153 BWC species from Facebook, and 1,000 BWC cases involving 104 BWC species from TaiRON. More than half of the BWC individuals from Facebook were not found dead when observed, whereas all records on TaiRON were dead individuals. The nationwide geographical coverage and the species compositions of the top 80% cumulative BWC individuals were generally similar between the two platforms. Moreover, the sampling completeness of the two platforms both exceeded 95% (Facebook: 98.0%; TaiRON: 96.0%). To our knowledge, this study is among the first to collect BWC data through social media posts, and our results show that the quantity and quality of Facebook data can be comparable to that of the well-developed citizen science platform TaiRON. Taken together, social media Facebook may not only serve as a promising tool for collecting BWC data, but also provide a platform for public education, which can benefit bird conservation. Finally, integrating data from different citizen science sources helps paint a more complete picture of BWC patterns, especially in understudied areas such as Asia.
Abnormally high exertional breathlessness predicts mortality in people referred for incremental cycle exercise testing
Authors: Elmberg Viktor , Zhou Xingwu , Lindow Thomas , Hedman Kristofer , Malinovschi Andrei , Lewthwaite Hayley , Jensen Dennis , Brudin Lars , Ekström Magnus
Published: April 2024

Background

Exertional breathlessness is a key symptom in cardiorespiratory disease and can be quantified using incremental exercise testing (IET), but its prognostic significance is unknown.

Research question

We evaluated the ability of abnormally high breathlessness intensity during IET to predict all-cause, respiratory, and cardiac mortality.

Study Design and Methods

Longitudinal cohort study of adults referred for cycle IET followed prospectively for mortality assessed using the Swedish National Causes of Death Registry. Abnormally high exertional breathlessness was defined as a breathlessness intensity response (Borg 0-10 scale) > the upper limit of normal (ULN) using published reference equations. Mortality was analyzed using multivariable Cox regression, unadjusted and adjusted for age, sex, and body mass index.

Results

Of the 13,506 people included (46% female, age 59±15 years), 2,867 (21%) had abnormally high breathlessness during IET. Over a median follow up of 8.0 years, 1,687 (12%) people died. No participant was lost to follow-up. Compared to those within normal predicted ranges, people with abnormally high exertional breathlessness had higher mortality from all causes (adjusted hazard ratio [aHR] 2.3, [95% confidence interval] 2.1-2.6), respiratory causes (aHR 5.2 [3.4-8.0]) and cardiac causes (aHR 3.0 [2.5-3.6]). Even among people with normal exercise capacity (defined as peak Watt ≥75% of predicted exercise capacity, n=10,284) those with abnormally high exertional breathlessness were at greater risk of all-cause mortality than people with exertional breathlessness within the normal predicted range (aHR 1.5 [1.2-1.8]).

Interpretation

Among people referred for cycle IET, abnormally high exertional breathlessness, quantified using healthy reference values, independently predicted all-cause, respiratory and cardiac mortality.
gRNAde: Geometric Deep Learning for 3D RNA inverse design
Authors: Joshi Chaitanya K. , Jamasb Arian R. , Viñas Ramon , Harris Charles , Mathis Simon V. , Morehead Alex , Anand Rishabh , Liò Pietro
Published: April 2024

Computational RNA design tasks are often posed as inverse problems, where sequences are designed based on adopting a single desired secondary structure without considering 3D conformational diversity. We introduce gRNAde, a geometric RNA design pipeline operating on 3D RNA backbones to design sequences that explicitly account for structure and dynamics. gRNAde uses a multi-state Graph Neural Network and autoregressive decoding to generates candidate RNA sequences conditioned on one or more 3D backbone structures where the identities of the bases are unknown. On a single-state fixed backbone re-design benchmark of 14 RNA structures from the PDB identified by Das et al. (2010), gRNAde obtains higher native sequence recovery rates (56% on average) compared to Rosetta (45% on average), taking under a second to produce designs compared to the reported hours for Rosetta. We further demonstrate the utility of gRNAde on a new benchmark of multi-state design for structurally flexible RNAs, as well as zero-shot ranking of mutational fitness landscapes in a retrospective analysis of a recent ribozyme. Experimental wet lab validation on 10 different structured RNA backbones finds that gRNAde has a success rate of 50% at designing pseudoknotted RNA structures, a significant advance over 35% for Rosetta. Open source code: https://github.com/chaitjo/geometric-rna-design
Flame retardant tetrabromobisphenol A (TBBPA) disrupts histone acetylation during zebrafish maternal-to-zygotic transition
Authors: Serradimigni Rosemaria , Rojas Alfredo , Leong Connor , Pal Uttam , Bryan Madeline , Sharma Sunil , Dasgupta Subham
Published: April 2024

3,3’,5.5’-Tetrabromobisphenol A (TBBPA) is a widely used brominated flame-retardant utilized in the production of electronic devices and plastic paints. The objective of this study is to use zebrafish as a model and determine the effects of TBBPA exposure on early embryogenesis. We initiated TBBPA exposures (0, 10, 20 and 40μM) at 0.75 h post fertilization (hpf) and monitored early developmental events such as cleavage, blastula and epiboly that encompass maternal-to-zygotic transition (MZT) and zygotic genome activation (ZGA). Our data revealed that TBBPA exposures induced onset of developmental delays by 3 hpf (blastula). By 5.5 hpf (epiboly), TBBPA-exposed (10-20 μM) embryos showed concentration-dependent developmental lag by up to 3 stages or 100% mortality at 40 μM. Embryos exposed to sublethal TBBPA concentrations from 0.75-6 hpf and raised in clean water to 120 hpf showed altered larval photomotor response (LPR), suggesting a compromised developmental health. To examine the genetic basis of TBBPA-induced delays, we conducted mRNA-sequencing on embryos exposed to 0 or 40 μM TBBPA from 0.75 hpf to 2, 3.5 or 4.5 hpf. Read count data showed that while TBBPA exposures had no overall impacts on maternal or maternal-zygotic genes, collective read counts for zygotically activated genes were lower in TBBPA treatment at 4.5 hpf compared to time-matched controls, suggesting that TBBPA delays ZGA. Gene ontology assessments for both time- and stage-matched differentially expressed genes revealed TBBPA-induced inhibition of chromatin assembly- a process regulated by histone modifications. Since acetylation is the primary histone modification system operant during early ZGA, we immunostained embryos with an H3K27Ac antibody and demonstrated reduced acetylation in TBBPA-exposed embryos. Leveraging in silico molecular docking studies and in vitro assays, we also showed that TBBPA potentially binds to P300- a protein that catalyzes acetylation- and inhibits P300 activity. Finally, we co-exposed embryos to 20 μM TBBPA and 50 μM n-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide (CTPB) -a histone acetyltransferase activator that promotes histone acetylation- and showed that TBBPA-CTPB co or pre-exposures significantly reversed TBBPA-only developmental delays, suggesting that TBBPA-induced phenotypes are indeed driven by repression of histone acetylation. Collectively, our work demonstrates that TBBPA disrupts ZGA and early developmental morphology, potentially by inhibiting histone acetylation. Future studies will focus on mechanisms of TBBPA-induced chromatin modifications.
Mosquitoes asses interspecific competition by larvae-released semiochemicals during oviposition habitat selection
Authors: Shteindel Nimrod , Gerchman Yoram , Silberbush Alon
Published: April 2024

Numerous species of animals alter their behavior in response to increasing competition. To do so, they must possess the ability to detect the presence and density of interspecific competitors. We studied the role of semiochemicals released by increasing densities of larvalCuliseta longiareolataMacquart on female oviposition habitat selection in two sets of field mesocosms. Similarly toC. longiareolatalarvae, subordinateCulex laticinctusEdwards are periphyton grazers who dwell in rain-filled pools in the Mediterranean region. We show thatC. laticinctusfemales oviposited significantly less in mesocosm pools that were treated with crowding signals originating fromC. longiareolatalarvae. In a second field experiment, we placed a similar number of larvae directly inside the 50 L mesocosms. These low-density mesocosms did not affectC. laticinctusoviposition but were attractive to conspecific oviposition. These results increase our understanding of the female’s ability to detect species-specific signals indicating increased larval competition.

Abstract Figure
Older Age and Vaccination Protect Against Transaminase Elevation in Pediatric SARS-CoV2
Authors: Ovale Antonia Fernandez , Charles Cassandra , Rosenbaum Janet , Villalba-Davila Priscila , Mora Mauricio , Sharma Shagun , Lemus Vivian Vega , Khandakar Saema , Wallach Thomas
Published: April 2024

Objectives

SARS-CoV2 infection is reported to induce transaminase elevations. There are case reports of severe liver injury in adult SARS-CoV2 patients and some have theorized that acute SARS-CoV2 infection may be a driver of severe liver injury in children. While pediatric hepatic injury has previously been described, clear shifts in immunogenic response secondary to prior immune exposure and vaccination since initial reports from 2020 warrant further evaluation. We sought to identify the impact of variant shifts and vaccination on this phenomenon in children.

Methods

A retrospective, cross-sectional study of pediatric SARS-CoV2 patients seen at two hospital facilities in an urban neighborhood in New York City between March 2020 and March 2022 was conducted via chart review. Data was extracted relating to patient’s demographics, clinical presentation, including the level of care and the laboratory results of comprehensive metabolic panels (CMP).

Results

133 pediatric cases were identified as having positive SARS-CoV2 and CMP obtained in the same visit. Patients were predominantly Black (79.2%) and non-Hispanic (87%) with a mean age of 9.2 years. Risk of transaminase elevation was increased in younger patients and patients with higher level of care. BMI was not a risk factor noted for transaminase elevation. Vaccination decreased degree, not incidence, of transaminase elevation but given low rates of vaccination unable to determine significance of protective efficacy.

Conclusions

Our study has identified a profound increased risk of transaminase elevation in younger patients, the absence of BMI as a correlating factor in our primarily Black patient population, a shift towards non-specific AST elevation with variant windows and a strong signal of vaccine protection.

What is Known

SARS-CoV2 can cause Transaminemia, and in rare cases, possible fulminant hepatic injury

Pediatric SARS-CoV2 infections are statistically milder than adult.

SARS-Cov2 case severity and complications like multisystem inflammatory syndrome in children have declined over time

What is New

With population immunity and variant shifts transaminase elevations increasingly may not be of hepatic origin

Risk of transaminase elevation is substantially higher in younger patients, and decreases with age

Vaccines are protective against degree of transaminase elevation, and likely against incidence of transaminase elevation, although further study is needed.

Article Summary

Cross sectional study of an urban pediatric population demonstrates SARS-CoV2 transaminase elevation linked with younger age, unvaccinated status, and higher level of care.
Paper 3: - Towards a Knowledge Sharing Maturity Model for medical imaging departments
Authors: Almashmoum Maryam , Cunningham James , Ainsworth John
Published: April 2024

Background

Knowledge sharing in medical imaging departments is being driven by the need to improve healthcare services, develop healthcare professionals’ skills, and reduce repetitive mistakes. It is considered an important step in the implementation of knowledge management solutions. By following a maturity model of knowledge sharing, knowledge sharing practices can be improved. The aim of this study was to develop a maturity model knowledge sharing in medical imaging department for helping managers to assess the level of maturity for knowledge sharing practices.

Objectives

In the modern healthcare institutions, improvements in healthcare professionals’ skills and healthcare services are often driven through practicing knowledge sharing behaviours. To understand the level of maturity of knowledge sharing, mangers can follow the indicators of maturity model knowledge sharing and its measurements in order to identify the current level and move to the next level.

Methods

This study was conducted in three stages: An ‘overview stage’ which highlighted the factors that affect knowledge sharing practices in medical imaging departments; an ‘Analysis factor stage’ which was designed to assess the factors that affect knowledge sharing by using a concurrent mixed method approach’s (questionnaires, and semi-structured interviews) in two medical imaging departments; and ‘Structuring maturity model knowledge sharing stage’, where a maturity model of knowledge sharing was developed based on the findings of the other stages.

Results

The model presented in this study includes 17 indicators divided into 11 components. Those components derived from the findings of the questionnaires and semi-structured interviews that were applied in the medical imaging departments. It consists of five maturity levels: initial, aware, define, managed, and optimised. In each level were included measurements in order to help managers to assess the current level by answering to the measurement’s questions.

Conclusion

This maturity model of knowledge sharing in medical imaging departments allows managers and policy makers to measure the maturity level of knowledge sharing in those departments. Although the model has been applied to the medical imaging departments, it might easily be modified to apply it to other institutions.
Long-lasting cigarette smoking alterations in immune function occur in cannabis smokers, possibly rendering them vulnerable to smoking-related tumors in later life
Authors: Lehrer Steven , Rheinstein Peter H.
Published: April 2024

Background

Active cigarette smoking leads to increased CXCL5 production. CXCL5 mediates the immune response by attracting immune cells to areas of inflammation. Elevated CXCL5 levels are associated with various inflammatory diseases and tumorigenesis. In addition, smoking is linked to an increase in the level of the cytokine CEACAM6 in the bloodstream of smokers. CEACAM6 is increased in pancreatic adenocarcinoma, breast cancer, non⍰small cell lung cancer, gastric cancer, colon cancer and other cancers and promotes tumor progression, invasion, and metastasis. Although cytokine secretion in the innate immune response returns to nonsmoker levels after quitting smoking, the effects on the adaptive response appear to persist for years or decades due to epigenetic memory. As a result, epigenetic changes induced by smoking may contribute to long-lasting alterations in immune function, including elevated CXCL5 and CEACAM6. The effects of cannabis smoking might be similar.

Methods

In the current study we used UK Biobank (UKB) data to assess the relationship of CXCL5, CEACAM6, and pulmonary function to cigarette and cannabis smoking. Our UK Biobank application was approved as UKB project 57245 (S.L., P.H.R.). Our analysis included all subjects with smoking and/or marijuana use data in the UK Biobank database. Circulating levels of CXCL5 and CEACAM6 were from UKB Olink data. Individual CXCL5 and CEACAM6 levels are NPX, Normalized Protein expression, Olink arbitrary unit in Log2 scale (Olink Proteomics AB, Uppsala, Sweden;http://www.olink.com).

Results

Current smokers and past smokers had elevated circulating levels of CXCL5 and CECAM6. In multivariate analysis, current, past, or no smoking history was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex. Frequency of cannabis use had a similar effect. In multivariate analysis, frequency of cannabis use was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex, and years between last cannabis use and enrollment in study.

Conclusion

we can confirm a previous report of epigenetic changes induced by cigarette smoking that may contribute to long-lasting alterations in immune function related to CXCL5 and CEACAM6. In addition, we have found that these same long-lasting smoking alterations in immune function related to CXCL5 and CEACAM6 occur in cannabis smokers, possibly rendering them vulnerable to smoking-related tumors in later life.
GLYCEMIC CONTROL AND PERIPHERAL ARTERIAL DISEASE IN DIABETIC FOOT PATIENTS
Authors: Carreño María Patricia Aragón , Figueroa Alfredo Aldama , de Jesús Fermín Rafael Martínez , Cvetkovic-Vega Aleksandar , Maguiña Quispe Jorge L.
Published: April 2024

Introduction

Diabetic foot is a severe complication of diabetes mellitus that can cause many amputations.

Objectives

To evaluate the association between glycemic control and peripheral arterial disease in patients with diabetic foot.

Materials and Methods

An analytical cross-sectional study was performed on patients diagnosed with diabetic foot with more than ten years of evolution of diabetes mellitus who were attended in the diabetic foot outpatient clinic of the Guillermo Almenara National Hospital between June 2015 and February 2017. Glycosylated hemoglobin (HbA1C) and ankle brachial index (ABI) were used to diagnose glycemic control and peripheral arterial disease, respectively. Generalized poisson log linear regression model was used to calculate the crude (cPR) and adjusted (aPR) prevalence ratios, with 95% confidence intervals, and a significance level of p < 0.05.

Results

226 patients were included in the study, finding 23% (n=52) with good glycemic control, and 44.7% (n=101) with peripheral arterial disease. The adjusted model found statistically significant associations for glycemic control, age, and sedentary lifestyle with peripheral arterial disease. Compared with patients with good glycemic control, those with poor glycemic control had a 34% higher probability to present peripheral arterial disease (aPR: 1.34, 95%CI: 1.01-1.79, p=0.045).

Conclusions

The prevalence of good glycemic control in the population with diabetic foot is low. Poor glycemic control was found to be independently associated with the presence of peripheral arterial disease.
Somatic epimutations enable single-cell lineage tracing in native hematopoiesis across the murine and human lifespan
Authors: Scherer Michael , Singh Indranil , Braun Martina , Szu-Tu Chelsea , Kardorff Michael , Rühle Julia , Frömel Robert , Beneyto-Calabuig Sergi , Raffel Simon , Rodriguez-Fraticelli Alejo , Velten Lars
Published: April 2024

Current approaches to lineage tracing of stem cell clones require genetic engineering or rely on sparse somatic DNA variants, which are difficult to capture at single-cell resolution. Here, we show that targeted single-cell measurements of DNA methylation at single-CpG resolution deliver joint information about cellular differentiation state and clonal identities. We develop EPI-clone, a droplet-based method for transgene-free lineage tracing, and apply it to study hematopoiesis, capturing hundreds of clonal trajectories across almost 100,000 single-cells. Using ground-truth genetic barcodes, we demonstrate that EPI-clone accurately identifies clonal lineages throughout hematopoietic differentiation. Applied to unperturbed hematopoiesis, we describe an overall decline of clonal complexity during murine ageing and the expansion of rare low-output stem cell clones. In aged human donors, we identified expanded hematopoietic clones with and without genetic lesions, and various degrees of clonal complexity. Taken together, EPI-clone enables accurate and transgene-free single-cell lineage tracing at scale.
Genes in Humans and Mice: Insights from Deep learning of 777K Bulk Transcriptomes
Authors: Su Zheng , Fang Mingyan , Smolnikov Andrei , Vafaee Fatemeh , Dinger Marcel E. , Oates Emily C.
Published: April 2024

Mice are widely used as animal models in biomedical research, favored for their small size, ease of breeding, and anatomical and physiological similarities to humans1,2. However, discrepancies between mouse gene experimental results and the actual behavior of human genes are not uncommon, despite their shared DNA sequence similarity3–8. This suggests that DNA sequence similarity does not always reliably predict functional similarity. On the other hand, RNA-level gene expression could offer additional information about gene function9,10. In this study, we undertook characterization and inter-species comparison of human and mouse genes by applying innovative deep learning methodologies to a large dataset of 410K human and 366K mouse bulk RNA-seq samples. This was achieved by using gene representations from our Transformer-based GeneRAIN model11,12. These gene representations aggregate information from large gene expression datasets, and provide insights beyond DNA sequence similarity. We identified 2,407 human-mouse homologous genes with high DNA similarity but distinct RNA characteristics, and showed that these genes are more likely to have differing disease/phenotype associations between the two species. Additionally, we found 3,070 homologous genes with low similarity at both the DNA and RNA levels, suggesting the highest risk of discrepancies in study results between the two species. We propose that this approach will support future decision making around whether the mouse will be an appropriate model for studying specific human genes, and whether the results of specific mouse gene studies are likely to be recapitulated in humans. Our methodological innovations offer valuable lessons for future deep learning applications in cross-species omics data. The interspecies gene relationship findings from our study also contribute valuable insights into the gene biology and evolution of the two species.
The histone demethylase JMJ27 acts during the UV-induced modulation of H3K9me2 landscape and facilitates photodamage repair
Authors: Johann to Berens Philippe , Peter Jackson , Koechler Sandrine , Bruggeman Mathieu , Staerck Sébastien , Molinier Jean
Published: April 2024

Plants have evolved sophisticated DNA repair mechanisms to cope with the deleterious effects of UV-induced DNA damage. Indeed, DNA repair pathways cooperate with epigenetic-related processes to efficiently maintain genome integrity. However, it remains to be deciphered how photodamages are recognized within different chromatin landscapes, especially in compacted genomic regions such as constitutive heterochromatin. We combined cytogenetics and epigenomics to identify that UV-C irradiation induces modulation of the main epigenetic mark found in constitutive heterochromatin, H3K9me2. We demonstrated that the histone demethylase, Jumonji27 (JMJ27), is responsible for the UV-induced reduction of H3K9me2 content at chromocenters. In addition, we identified that JMJ27 forms a complex with the photodamage recognition factor, DNA Damage Binding protein 2 (DDB2), and that the fine tuning of H3K9me2 contents orchestrates DDB2 dynamics on chromatin in response to UV-C exposure. Hence, this study uncovers the existence of an interplay between photodamage repair and H3K9me2 homeostasis.
Enhancing altruism by electrically augmenting frontoparietal gamma-band phase coupling
Authors: Hu Jie , Moisa Marius , Ruff Christian C.
Published: April 2024

Cooperation, productivity, and cohesion in human societies depend on altruism, the tendency to share resources with others even though this is costly. While altruism is a widely shared social norm, people vary strongly in their inclination to behave altruistically, in particular across situations with different types of inequality in resource distribution. What neurobiological factors underlie this variability? And can these be targeted by interventions to enhance altruistic behavior? Here, we build on recent EEG findings that altruistic choices during disadvantageous inequality correlate with oscillatory gamma-band coherence between frontal regions (representing other’s interest) and parietal regions (representing neural evidence accumulation). We apply a transcranial alternating current stimulation (tACS) protocol designed to exogenously enhance this fronto-parietal coherence and find that this leads to increased altruism, specifically during disadvantageous inequality as hypothesized based on the EGG findings. Computational modeling reveals that this transcranial entrainment does not just add noise to the decision process but specifically increases the weight individuals assign to other-regarding concerns during choices. Our findings show that altruism can be enhanced by neurostimulation designed to enhance oscillatory synchronization between frontal and parietal areas. This establishes a neural basis for altruism and identifies a neural target for interventions aimed at improving prosocial behavior.
IS-PRM-based peptide targeting informed by long-read sequencing for alternative proteome detection
Authors: Korchak Jennifer A. , Jeffery Erin D. , Bandyopadhyay Saikat , Jordan Ben T. , Lehe Micah , Watts Emily F. , Fenix Aidan , Wilhelm Mathias , Sheynkman Gloria M.
Published: April 2024

Alternative splicing is a major contributor of transcriptomic complexity, but the extent to which transcript isoforms are translated into stable, functional protein isoforms is unclear. Furthermore, detection of relatively scarce isoform-specific peptides is challenging, with many protein isoforms remaining uncharted due to technical limitations. Recently, a family of advanced targeted MS strategies, termed internal standard parallel reaction monitoring (IS-PRM), have demonstrated multiplexed, sensitive detection of pre-defined peptides of interest. Such approaches have not yet been used to confirm existence of novel peptides. Here, we present a targeted proteogenomic approach that leverages sample-matched long-read RNA sequencing (LR RNAseq) data to predict potential protein isoforms with prior transcript evidence. Predicted tryptic isoform-specific peptides, which are specific to individual gene product isoforms, serve as “triggers” and “targets” in the IS-PRM method, Tomahto. Using the model human stem cell line WTC11, LR RNAseq data were generated and used to inform the generation of synthetic standards for 192 isoform-specific peptides (114 isoforms from 55 genes). These synthetic “trigger” peptides were labeled with super heavy tandem mass tags (TMT) and spiked into TMT-labeled WTC11 tryptic digest, predicted to contain corresponding endogenous “target” peptides. Compared to DDA mode, Tomahto increased detectability of isoforms by 3.6-fold, resulting in the identification of five previously unannotated isoforms. Our method detected protein isoform expression for 43 out of 55 genes corresponding to 54 resolved isoforms. This LR RNA seq-informed Tomahto targeted approach, called LRP-IS-PRM, is a new modality for generating protein-level evidence of alternative isoforms – a critical first step in designing functional studies and eventually clinical assays.
Combinatorial expression of neurexin genes regulates glomerular targeting by olfactory sensory neurons
Authors: Park Sung Jin , Wang I-Hao , Lee Namgyu , Jiang Hao-Ching , Uemura Takeshi , Futai Kensuke , Kim Dohoon , Macosko Evan , Greer Paul
Published: April 2024

Precise connectivity between specific neurons is essential for the formation of the complex neural circuitry necessary for executing intricate motor behaviors and higher cognitive functions. Whiletrans-interactions between synaptic membrane proteins have emerged as crucial elements in orchestrating the assembly of these neural circuits, the synaptic surface proteins involved in neuronal wiring remain largely unknown. Here, using unbiased single-cell transcriptomic and mouse genetic approaches, we uncover that the neurexin family of genes enables olfactory sensory neuron (OSNs) axons to form appropriate synaptic connections with their mitral and tufted (M/T) cell synaptic partners, within the mammalian olfactory system. Neurexin isoforms are differentially expressed within distinct populations of OSNs, resulting in unique pattern of neurexin expression that is specific to each OSN type, and synergistically cooperate to regulate axonal innervation, guiding OSN axons to their designated glomeruli. This process is facilitated through the interactions of neurexins with their postsynaptic partners, including neuroligins, which have distinct expression patterns in M/T cells. Our findings suggest a novel mechanism underpinning the precise assembly of olfactory neural circuits, driven by thetrans-interaction between neurexins and their ligands.
TDG orchestrates ATF4-dependent gene transcription during retinoic acid-induced cell fate acquisition
Authors: Turpin Marion , Madigou Thierry , Bizot Maud , Acker Rachael , Avner Stephane , Benoît Gérard , Braud Martin , Fourgeux Cynthia , Palierne Gaëlle , Poschmann Jeremie , Sawvell Katie , Watrin Erwan , Péron Christine Le , Salbert Gilles
Published: April 2024

Acquisition of cell identity is associated with a remodeling of the epigenome in part through active DNA demethylation. The T:G mismatch DNA glycosylase (TDG) participates to this process by removing 5-methylcytosines that have been oxidized by Ten-Eleven-Translocation (TET) enzymes. Despite this well-defined molecular function, a comprehensive view of the biological function of TDG is still lacking, especially during cell differentiation. Here, we combined transcriptomic and epigenomic approaches in aTdgknock-out epiblast stem-like cell model to decipher TDG function in pluripotent cells and their retinoic acid-induced progeny. We determined that TDG occupies a majority of active promoters, a large fraction of which are also engaged by the transcription factor ATF4. Consistently, neural fate commitment upon retinoic acid treatment is associated with a TDG-dependent sustained expression of ATF4-dependent genes, in relation with a TDG-associated nucleosome positioning at promoters. We further evidenced that TDG maintains ATF4 pathway activity by positively regulating the mammalian target of rapamycin complex 1 (mTORC1), favoring neural cell fate commitment. These observations highlight the central role of TDG in cell differentiation and support a model linking metabolic reprogramming to cell fate acquisition.
Identification of cell-type-specific response to silicon treatment in soybean leaves through single nucleus RNA-sequencing
Authors: Devkar Vikas , D’Agostino Leonidas , Kshetry Arjun Ojha , Yong Lenin , Nadaf Altafhusain B , Thirumalaikumar VP , Skirycz Aleksandra , Ma Jianxin , Stupar Robert M. , Herrera-Estrella Luis , Deshmukh Rupesh , Patil Gunvant B.
Published: April 2024

In agriculture, mineral nutrients uptake and deposition profoundly influence plant development, stress resilience, and productivity. Despite its classification as a non-essential element, silicon (Si) is crucial in plant physiology, particularly in defense response and stress mitigation. While genetic and molecular mechanisms of Si uptake and transport are well-studied in monocots, particularly rice, its role in dicot species, such as soybean, remains unclear at the cellular and molecular levels. Traditional bulk transcriptomics methods lack the resolution to uncover cellular heterogeneity. Here, we present a study by utilizing single-nucleus RNA sequencing (snRNA-seq) to dissect cellular responses to Si accumulation in soybean leaves. Our analysis revealed distinct cellular populations, including a novel Si-induced cell cluster within vascular cells, suggesting a specific mechanism of Si distribution. Si treatment induced the expression of defense-related genes, particularly enriched in vascular cells, highlighting their specialized role in activating plant defense mechanisms. Moreover, Si modulated the expression of genes involved in RNA silencing, phytoalexin biosynthesis, and immune receptor signaling, suggesting a mechanism of transcriptional priming of genes involved in defense responses. We further investigated putative Si transporters, revealing differential expression patterns in response to Si treatment, suggesting presence of active and gradient-based transport mechanisms. Our findings shed light on the vital biotic stress regulatory networks governed by Si treatment in soybean leaves, paving potential strategies for enhancing stress tolerance and agronomic performance in crops.
Acute and Chronic Neural and Glial Response to Mild Traumatic Brain Injury in the Hippocampus
Authors: Dougan Carey E. , Roberts Brandon L. , Crosby Alfred J. , Karatsoreos Ilia , Peyton Shelly R.
Published: April 2024

Traumatic brain injury (TBI) is an established risk factor for developing neurodegenerative disease. However, how TBI leads from acute injury to chronic neurodegeneration is limited to post-mortem models. There is a lack of connections betweenin vitroandin vivoTBI models that can relate injury forces to both macroscale tissue damage and brain function at the cellular level. Needle-induced cavitation (NIC) is a technique that can produce small cavitation bubbles in soft tissues, which allows us to relate small strains and strain rates in living tissue to ensuing acute and chronic cell death, tissue damage, and tissue remodeling. Here, we applied NIC to mouse brain slices to create a new model of TBI with high spatial and temporal resolution. We specifically targeted the hippocampus, which is a brain region critical for learning and memory and an area in which injury causes cognitive pathologies in humans and rodent models. By combining NIC with patch-clamp electrophysiology, we demonstrate that NIC in the Cornu Ammonis (CA)3 region of the hippocampus dynamically alters synaptic release onto CA1 pyramidal neurons in a cannabinoid 1 receptor (CB1R)-dependent manner. Further, we show that NIC induces an increase in extracellular matrix proteins associated with neural repair that is mitigated by CB1R antagonism. Together, these data lay the groundwork for advanced approaches in understanding how TBI impacts neural function at the cellular level, and the development of treatments that promote neural repair in response to brain injury.

SIGNIFICANCE

Current models of mild TBI (mTBI) cannot relate injury forces to both macroscale tissue damage and brain function at the cellular level. We combine a microscale injury model inex vivobrain slices while simultaneously recording glutamatergic inputs onto CA1 hippocampal pyramidal neurons. Post-injury examination of chronic tissue regeneration by astrocytes allow us to connect acute neuronal signaling responses to chronic fibrosis after TBI. These studies provide a new tool for understanding the physiological and molecular responses to TBI and lay the groundwork for future experiments unraveling the synaptic mechanisms that mediate these responses seconds, minutes, and days following injury.
Unilateral auditory deprivation reveals brainstem origin of a sensitive period for spatial hearing
Authors: Anbuhl Kelsey L. , Ferber Alexander T. , Brown Andrew D. , Benichoux Victor , Greene Nathaniel T. , Tollin Daniel J.
Published: April 2024

Early sensory experience can exert lasting perceptual consequences. For example, a brief period of auditory deprivation early in life can lead to persistent spatial hearing deficits. Some forms of hearing loss (i.e., conductive; CHL) can distort acoustical cues needed for spatial hearing, which depend on inputs from both ears. We hypothesize that asymmetric acoustic input during development disrupts auditory circuits that integrate binaural information. Here, we identify prolonged maturation of the binaural auditory brainstem in the guinea pig by tracking auditory evoked potentials across development. Using this age range, we induce a reversible unilateral CHL and ask whether behavioral and neural maturation are disrupted. We find that developmental CHL alters a brainstem readout of binaural function which is not observed when the CHL is induced in adulthood. Startle-based behavioral measures reveal poorer spatial resolution of sound sources, but only for high-frequency sound stimuli. Finally, single-unit recordings of auditory midbrain neurons reveal significantly poorer neural acuity to a sound location cue that largely depends on high-frequency sounds. Thus, these findings show that unilateral deprivation can disrupt developing auditory circuits that integrate binaural information and may give rise to lingering spatial hearing deficits.
Single-cell transcriptional landscape of temporal neutrophil response to burn wound in larval zebrafish
Authors: Hou Yiran , Khatri Parth , Rindy Julie , Schultz Zachery , Gao Anqi , Chen Zhili , Gibson Angela LF , Huttenlocher Anna , Dinh Huy Q.
Published: April 2024

Neutrophils accumulate early in tissue injury. However, the cellular and functional heterogeneity of neutrophils during homeostasis and in response to tissue damage remains unclear. Here, we use larval zebrafish to understand neutrophil responses to thermal injury. Single-cell transcriptional mapping of myeloid cells during a 3-day time course in burn and control larvae revealed distinct neutrophil subsets and their cell-cell interactions with macrophages across time and conditions. The trajectory formed by three zebrafish neutrophil subsets resembles human neutrophil maturation, with varying transition patterns between conditions. Through ligand-receptor cell-cell interaction analysis, we found neutrophils communicate more in burns in a pathway and temporal manner. Finally, we identified the correlation between zebrafish myeloid signatures and human burn severity, establishing GPR84+ neutrophils as a potential marker of early innate immune response in burns. This work builds the molecular foundation and a comparative single-cell genomic framework to identify neutrophil markers of tissue damage using model organisms.
Identification of Large Japanese field mouseApodemus speciosusfood plant resources in an industrial green space using DNA metabarcoding
Authors: Fujii Taichi , Kawamoto Hirokazu , Shirako Tomoyasu , Nakamura Masatoshi , Minami Motoyasu
Published: April 2024

DNA metabarcoding was employed to identify the food plant resources of the Large Japanese field mouse Apodemus speciosus, inhabiting an artificial green space on reclaimed land on the Chita Peninsula in Aichi Prefecture, Central Japan, from 2012 to 2014. DNA metabarcoding was performed using high-throughput sequencing of partial rbcL sequences extracted from feces samples collected in the study area. The obtained sequences, which were analyzed using a constructed local database, revealed that a total of 72 plant taxa were utilized as food plant resources by A. speciosus. Of these plant taxa, 43 could be assigned to species (59.7%), 16 to genus (22.2%), and 13 to family (18.1%). Of the 72 plant taxa identified in this study, the dominant families throughout all collection periods were Lauraceae (81.0% of 100 fecal samples), followed by Fagaceae (70.0%), Rosaceae (68.0%), and Oleaceae (48.0%). Fifty of the 72 plant taxa identified as food plant resources were woody plants. An analysis employing rarefaction techniques for each season in the study site indicated comprehensive coverage of the food plant resources, ranging from 86.4% in winter to 93.6% in spring. Further, 96.5% of the food plant taxa were found throughout the study period. The findings showed that DNA metabarcoding using a local database constructed from the National Center for Biotechnology Information (NCBI) database and field surveys was effective for identifying the dominant food plants in the diet of A. speciosus. The results of this study provided basic information that can be applied to formulation and implementation of management and conservation strategies for local wildlife.
Tuning Collective Behaviour in Zebrafish with Genetic Modification
Authors: Yang Yushi , Kawafi Abdelwahab , Tong Qiao , Hammond Chrissy L. , Kague Erika , Royall C. Patrick
Published: April 2024

Zebrafish collective behaviour is widely used to assess their physical and mental state, serving as a valuable tool to assess the impact of ageing, disease genetics, and the effect of drugs. The essence of these macroscopic phenomena can be represented by active matter models, where the individuals are abstracted as interactive self-propelling agents. The behaviour of these agents depends on a set of parameters in a manner reminiscent of those between the constituents of physical systems. In a few cases, the system may be controlled at the level of the individual constituents such as the interactions between colloidal particles, or the enzymatic behaviour ofde novoproteins. Usually, however, while the collective behaviour may be influenced by environmental factors, it typically cannot be changed at will. Here, we challenge this scenario in a biological context by genetically modifying zebrafish. We thus demonstrate the potential of genetic modification in the context of controlling the collective behaviour of biological active matter systems at the level of the constituents, rather than externally. In particular, we probe the effect of the lack ofcol11a2gene in zebrafish, which causes the early onset of osteoarthritis. The resultingcol11a2 -/-zebrafish exhibited compromised vertebral column properties, bent their body less while swimming, and took longer to change their orientations. Surprisingly, a group of 25 mutant fish exhibited more orderly collective motion than the wildtype. We show that the collective behaviour of wildtype andcol11a2 -/-zebrafish are captured with a simple active matter model, in which the mutant fish are modelled by self–propelling agents with a higher orientational noise on average. In this way, we demonstrate the possibility of tuning a biological system, changing the state space it occupies when interpreted with a simple active matter model.