bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of chronological age from resting-state EEG power in the first three years of life
Authors: An Winko W. , Bhowmik Aprotim C. , Nelson Charles A. , Wilkinson Carol L.
Published: June 2024

The infant brain undergoes rapid and significant developmental changes in the first three years of life. Understanding these changes through the prediction of chronological age using neuroimaging data can provide insights into typical and atypical brain development. We utilized longitudinal resting-state EEG data from 457 typically developing infants, comprising 938 recordings, to develop age prediction models. The multilayer perceptron model demonstrated the highest accuracy with an R2of 0.82 and a mean absolute error of 92.4 days. Aperiodic offset and periodic theta, alpha, and beta power were identified as key predictors of age via Shapley values. Application of the model to EEG data from infants later diagnosed with autism spectrum disorder or Down syndrome revealed significant underestimations of chronological age. This study establishes the feasibility of using EEG to assess brain maturation in early childhood and supports its potential as a clinical tool for early identification of alterations in brain development.
Evaluation of SURUS: a Named Entity Recognition System to Extract Knowledge from Interventional Study Records
Authors: Peeters Casper , Vijverberg Koen , Pouwer Marianne , Westerman Bart , Boot Maikel , Verberne Suzan
Published: June 2024

BACKGROUND

Medical decision-making is commonly guided by systematic analysis of peer-reviewed scientific literature, published as systematic literature reviews (SLRs). These analyses are cumbersome to conduct as they require large amounts of time and subject matter expertise to be available. Automated extraction of key datapoints from clinical publications could speed up the process of systematic literature review assembly. To this end, we built, trained and validated SURUS, a named entity recognition (NER) system comprised of a Bidirectional Encoder Representations from Transformers (BERT) model trained on a highly granular dataset. The aim of this study was to assess the quality of classification of critical elements in clinical study abstracts by SURUS, in particular the patient, intervention, comparator and outcome (PICO) elements and elements of study design.

DATASET & METHODS

The PubMedBERT-based model was trained and evaluated using a dataset of 400 interventional study abstracts, manually annotated by experts using 25 labels with a total of 39,531 annotations according to a strict annotation guideline, with Cohen’s κ inter-annotator agreement of 0.81. We evaluated in-domain quality, and assessed out-of-domain quality of the system by testing it on out-of-domain abstracts of other disease areas and observational study types. Finally, we tested the utility of SURUS by comparing its predictions to expert-assigned PICO and study design (PICOS) classifications.

RESULTS

The SURUS NER system achieved an overall F1 score of 0.95, with minor deviation between labels. In addition, SURUS achieved a NER F1 of 0.90 for out-of-domain therapeutic area abstracts and 0.84 for observational study abstracts. Finally, SURUS showed considerable utility when compared to expert-assigned PICOS classifications of interventional studies, with an F1 of 0.89 and a recall of 0.96.

CONCLUSION

To our knowledge, with an F1 score of 0.95, SURUS ranks among the best-performing models available to date for conducting exhaustive systematic literature analyses. A strict guideline and high inter-annotation agreement resulted in high-quality in-domain medical entity of a finetuned BERT-based model, which was largely preserved during extensive out-of-domain evaluation, indicating its utility across other indication areas and study types. Current approaches in the field lack the granularity in training data and versatility demonstrated by the SURUS approach, thereby making the latter the preferred choice for automated extraction and classification tasks in the clinical literature domain. We think that this approach sets a new standard in medical literature analysis and paves the way for creating highly granular datasets of labelled entities that can be used for downstream analysis outside of traditional SLRs.
The concentration of tuberculosis within Paraguay’s incarcerated and Indigenous populations, 2018-2022
Authors: Medina Angélica , Sussman Jacob , Sosa Natalia , Valdez Melissa , Andrews Jason R. , Croda Julio , Sanabria Gladys Estigarribia , Sequera Guillermo , Aguirre Sarita , Walter Katharine S.
Published: June 2024

While incidence of tuberculosis (TB) has decreased globally, in Paraguay, considered a medium-incidence country by the WHO, TB incidence has increased slightly from 42 per 100,000 in 2010 to 46 per 100,000 in 2022. We conducted a retrospective study of TB cases notified to the Paraguay National Program for Tuberculosis Control (NPTC) from 2018 to 2022 and quantified trends in specific populations identified as vulnerable. Of the 13,725 TB cases notified in Paraguay from 2018 to 2022, 2,331 (17%) occurred among incarcerated individuals and 1,743 (12.7%) occurred among self-identified Indigenous individuals. In 2022, the relative risk of TB was 87 and 6.4 among the incarcerated and Indigenous populations, compared with the non-incarcerated and non-Indigenous populations respectively. We found significant heterogeneity in TB incidence across Paraguay’s 17 departments. Our findings highlight the urgency of expanding access to TB diagnosis, treatment, and prevention in populations at heightened risk of TB in Paraguay.
ACUTE KIDNEY INJURY AS A PREDICTOR OF IN-HOSPITAL MORTALITY IN PATIENTS WITH A DIAGNOSIS OF SEVERE COVID-19
Authors: Ordinola Anthonela Cruz , Arriola Carlos Fajardo , Ato Raúl Sandoval
Published: June 2024

OBJECTIVE

Determine if Acute Kidney Injury (AKI) is a predictor of In-hospital Mortality in severe Covid-19 patients.

METHODS

A retrospective cohort study was carried out with severe Covid-19 patients from the Hospital de la Amistad Perú - Corea Santa Rosa II - Piura, using a multivariate analysis with the bivariate logistic regression technique and the method = Advance by steps (ratio of likelihood), to calculate a predictive model for Mortality in Covid-19 patients exposed to ARI.

RESULTS

Mortality was higher in the cohort exposed to ARI (95% vs 71.9%) and a 5-fold RR of death in the patient exposed to ARI compared to the Covid-19 patient not exposed to ARI.

CONCLUSION

Exposure to ARI increases the risk of mortality by 5 times, increasing the risk of mortality based on the increase in the SOFA score upon admission to the ICU and increase in mg/dl of C-Reactive Protein.
Surgical Decision-Making in Neonates with Borderline Left Ventricular Hypoplasia without Significant Aortic or Mitral Valve Stenosis using Cardiovascular Magnetic Resonance
Authors: House Aswathy Vaikom , Singh Aakansha , Sapruangrang Ankavipar , Jaeggi Edgar , Barron David J. , Lam Christopher Z. , Yoo Shi-Joon
Published: June 2024

Background

Most patients with significant left ventricular (LV) hypoplasia undergo single ventricle (SV) palliation, but biventricular (Bi-V) repair is viable in some patients with borderline LV hypoplasia. We sought to identify CMR (cardiovascular magnetic resonance) criteria predictive of successful primary Bi-V repair in neonates with borderline LV hypoplasia without significant stenosis of the mitral valve (MV) and aortic valve (AV), and to determine reasons for reintervention after successful Bi-V repair.

Methods

This retrospective study included all patients with borderline LV hypoplasia who underwent CMR from 2003-2024 for surgical decision-making. Patients with abnormal segmental connections, atrioventricular septal defects, unrestrictive ventricular septal defects, those with more than mild MV stenosis (mean Doppler flow gradient > 5 mmHg) and/or more than mild AV stenosis (peak Doppler flow gradient >20 mmHg) were excluded. Patients were divided into two groups based on initial intervention - primary Bi-V repair and hybrid/ other staging procedure. Outcomes were categorized as successful primary Bi-V repair, successful staged Bi-V repair and failure to achieve Bi-V repair (hybrid followed by SV palliation, transplant, death). Fisher exact test and Mann-Whitney U test was utilized to explore potential relationships. ROC curves were used to test diagnostic accuracy of parameters to predict successful primary Bi-V repair.

Results

Among 37 patients meeting the inclusion criteria, 23 (62%) patients underwent successful primary Bi-V repair, 8 (22%) underwent staged Bi-V repair, 6 (16%) failed to achieve Bi-V repair. Patients who underwent successful primary/ staged Bi-V repair had higher values for left ventricular diastolic volume index (LVEDVi 28 mL/m2vs. 17.4.00 mL/m2; p <0.002), higher blood flow volume through the ascending aorta (QAo:1.99 L/min/m2vs. 0.97 L/min/m2, p <0.012), and QAo/ superior vena cava (QSVC) flow ratio (1.44 vs. 0.85, p =0.034) compared to those who had failure to achieve Bi-V repair. CMR LVEDVi cutoff of CMR 27 mL/m², had 87% sensitivity and 79% specificity with an AUC of 87.6% and QAothreshold of 1.9 L/min/m2had 65.2% sensitivity and 92.9% specificity (AUC: 86.0%) to predict successful primary Bi-V repair. Of 31 patients with primary or staged Bi-V repair, 7 (22%) underwent reinterventions for LVOT obstruction followed by mitral stenosis.

Conclusions

CMR plays a critical role in pre-operative evaluation, surveillance and decision-making in patients with borderline LV hypoplasia. In patients with borderline LV hypoplasia without MV/AV stenosis, successful primary Bi-V repair can be achieved when the CMR-derived LVEDVi is >27 mL/m2and QAois > 1.99 L/min/m2.
Direct observation of fluorescent proteins in gels: a rapid cost-efficient, and quantitative alternative to immunoblotting
Authors: Sanial Matthieu , Miled Ryan , Alves Marine , Claret Sandra , Joly Nicolas , Proux-Gillardeaux Véronique , Plessis Anne , Léon Sébastien
Published: June 2024

The discovery of Green Fluorescent Protein (GFP) and its derivatives has revolutionized cell biology. These fluorescent proteins (FPs) have enabled the real-time observation of protein localization and dynamics within live cells. Applications of FP vary from monitoring gene/protein expression patterns, visualizing protein-protein interactions, measuring protein stability, assessing protein mobility and creating biosensors. The utility of FPs also extends to biochemical approaches through immunoblotting and proteomic analyses, aided by anti-FP antibodies and nanobodies. FPs are notoriously robust proteins with a tightly folded domain that confers a strong stability and a relative resistance to degradation and denaturation. In this study, we report that various green, orange and red FPs can be maintained in a native, fluorescent state during the entire process of protein sample extraction, incubation with sample buffer, loading and migration on SDS-PAGE with only minor adaptations of traditional protocols. This protocol results in the ability to detect and quantify in-gel fluorescence (IGF) of endogenously-expressed proteins tagged with FPs directly after migration, using standard fluorescence-imaging devices. This approach eliminates the need for antibodies and chemiluminescent reagents, as well as the time-consuming steps inherent in immunoblotting such as transfer onto a membrane and antibody incubations. Overall, IGF detection provides clearer data with less background interference, a sensitivity comparable or better to antibody-based detection, a better quantification and a broader dynamic range. After fluorescence imaging, gels can still be used for other applications such as total protein staining or immunoblotting if needed. It also expands possibilities by allowing the detection of FPs for which antibodies are not available. Our study explores the feasibility, limitations, and applications of IGF for detecting endogenously expressed proteins in cell extracts, providing insights into sample preparation, imaging conditions, and sensitivity optimizations, and potential applications such as co-immunoprecipitation experiments.
Robust encoding of acoustic identity in alpaca hums - a basis for individual recognition
Authors: Wierucka Kaja , Leu Stephan T.
Published: June 2024

Individual recognition is an important element of social interactions among animals. While the presence of individually distinct vocalisations (providing a basis for individual recognition) has been widely tested across species, information about which components of a call encode this information is lacking. We investigated whether female alpaca (Vicugna pacos) vocalisations, particularly their hums, encode information about individual identity and explored which parameters contribute to this encoding. We recorded vocalisations from 9 adult female alpaca and extracted both spectro-temporal features (frequencies and duration) and mel-frequency cepstral coefficients (MFCC). Random forest analyses revealed clear individual differences in both datasets, with the spectro-temporal features allowing for slightly more accurate classification than MFCC (71% and 66.5% accuracy for spectro-temporal features and MFCC, respectively). These robust acoustic identities have the potential to provide a basis for individual recognition in alpaca, which could have important flow on effects for alpaca communication, as it allows receivers to modulate their response to the caller’s identity. Alpaca, as herd-living and vocal animals, provide an excellent model system for better understanding the mechanisms, causes and consequences of recognition and inter-individual communication.
Vaccine strains of Rift Valley fever virus exhibit attenuation at the maternal-fetal placental interface
Authors: McMillen Cynthia M. , Megli Christina , Radisic Rebecca , Skvarca Lauren B. , Hoehl Ryan M. , Boyles Devin A. , McGaughey Jackson J. , Bird Brian H. , McElroy Anita K. , Hartman Amy L.
Published: June 2024

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal-fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and ΔNSm infection, while live attenuated RVFV vaccines (LAVs; MP-12, ΔNSs, and ΔNSs/ΔNSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent in the maternal-facing side. Type-I and type-III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal-fetal interface.

Teaser

Vaccine strains of Rift Valley fever virus have reduced infection and replication capacity in mammalian placenta
Systems genomics of salinity stress response in rice
Authors: Gupta Sonal , Groen Simon C. , Zaidem Maricris L. , Sajise Andres Godwin C. , Calic Irina , Natividad Mignon A. , McNally Kenneth L. , Vergara Georgina V. , Satija Rahul , Franks Steven J. , Singh Rakesh K. , Joly-Lopez Zoé , Purugganan Michael D.
Published: June 2024

Populations can adapt to stressful environments through changes in gene expression. However, the fitness effect of gene expression in mediating stress response and adaptation remains largely unexplored. Here, we use an integrative field dataset obtained from 780 plants ofOryza sativassp. indica(rice) grown in a field experiment under normal or moderate salt stress conditions to examine selection and evolution of gene expression variation under salinity stress conditions. We find that salinity stress induces increased selective pressure on gene expression. Further, we show thattrans-eQTLs rather thancis-eQTLs are primarily associated with rice’s gene expression under salinity stress, potentially via a few master-regulators. Importantly, and contrary to the expectations, we find thatcis-transreinforcement is more common thancis-transcompensation which may be reflective of rice diversification subsequent to domestication. We further identify genetic fixation as the likely mechanism underlying this compensation/reinforcement. Additionally, we show thatcis- andtrans-eQTLs are under balancing and purifying selection, respectively, giving us insights into the evolutionary dynamics of gene expression variation. By examining genomic, transcriptomic, and phenotypic variation across a rice population, we gain insights into the molecular and genetic landscape underlying adaptive salinity stress responses, which is relevant for other crops and other stresses.
LC-SRM combined with machine learning enables fast identification and quantification of bacterial pathogens in urinary tract infections
Authors: Gotti Clarisse , Roux-Dalvai Florence , Bérubé Ève , Lacombe-Rastoll Antoine , Leclercq Mickaël , Jacob Cristina C. , Boissinot Maurice , Martins Claudia , Wijeratne Neloni R. , Bergeron Michel G. , Droit Arnaud
Published: June 2024

Urinary tract infections (UTIs) are a worldwide health problem. Fast and accurate detection of bacterial infection is essential to provide appropriate antibiotherapy to patients and to avoid the emergence of drug-resistant pathogens. While the gold standard requires 24h to 48h of bacteria culture prior MALDI-TOF species identification, we propose a culture-free workflow, enabling a bacterial identification and quantification in less than 4 hours using 1mL of urine. After a rapid and automatable sample preparation, a signature of 82 bacterial peptides, defined by machine learning, was monitored in LC-MS, to distinguish the 15 species causing 84% of the UTIs. The combination of the sensitivity of the SRM mode on a triple quadrupole TSQ Altis instrument and the robustness of capillary flow enabled us to analyze up to 75 samples per day, with 99.2% accuracy on bacterial inoculations of healthy urines. We have also shown our method can be used to quantify the spread of the infection, from 8×104to 3×107CFU/mL. Finally, the workflow was validated on 45 inoculated urines and on 84 UTI-positive urine from patients, with respectively 93.3% and 87.1% of agreement with the culture-MALDI procedure at a level above 1×105CFU/mL corresponding to an infection requiring antibiotherapy.

HIGHLIGHTS

– LC-MS-SRM and machine learning to identify and quantify bacterial species of UTI

– Fast sample preparation without bacterial culture and high-throughput MS analysis

– Accurate quantification through calibration curves for 15 species of UTIs

– Validation on inoculations (93% accuracy) and on patients specimens (87% accuracy)
Estrous phase during fear extinction modulates fear relapse through a nigrostriatal dopamine pathway
Authors: Hohorst Alyssa A , Tanner Margaret K , Han Rebecca , Korth Kamryn , Westerman Jessica D , Mendoza Carolina Sanchez , Dryden Miles Q , Alverez Lareina , Abdul Remla , Loetz Esteban C , Oleson Erik B , Greenwood Benjamin N
Published: June 2024

Elevated ovarian hormones during fear extinction can enhance fear extinction memory retention and reduce renewal, but the mechanisms remain unknown. Ovarian hormones modulate dopamine (DA) transmission, a key player in fear extinction. In males, stimulation of substantia nigra (SN) DA neurons during fear extinction reduces renewal; an effect mimicked by a DA D1 receptor agonist into the dorsolateral striatum (DLS). The current studies tested the role of the SN-DLS pathway in estrous cycle-modulation of fear extinction and relapse. In cycling female, Long-Evans rats, fear extinction during proestrus or estrus (Pro/Est; high hormones) resulted in less relapse (renewal and spontaneous recovery) compared to males or females in metestrus or diestrus (Met/Di; low hormones). This effect was mimicked by estradiol (E2) administration to ovariectomized rats. Females in Pro/Est had greater fear extinction-induced cFos within SN DA neurons compared to males. Similarly, fast scan cyclic voltammetry revealed that electrically-evoked DA release in the DLS is potentiated by E2 and is greater during Pro/Est compared to Met/Di. An inhibitory intersectional chemogenetic approach targeting the SN-DLS pathway suppressed electrically-evoked DA release in the DLS and restored fear renewal in females exposed to simultaneous fear extinction and SN-DLS inhibition during Pro/Est. Conversely, chemogenetic stimulation of the SN-DLS pathway during extinction reduced fear renewal in males. These data suggest that levels of ovarian hormones present during fear extinction modulate relapse through a SN-DLS pathway, and that the SN-DLS pathway represents a novel target for the reduction of fear relapse in both sexes.
The double-edged sword of urban life: Invasive grey squirrels perceive foraging as safer close to roads under noisier conditions, yet riskier when noise is inconsistent
Authors: Thompson Kristin P. J. , Dall Sasha R.X.
Published: June 2024

Mortality risk influences decisions of foraging animals such that foraging and feeding behaviours are usually biased towards habitats where benefits of feeding outweigh risks. Human activity and associated disturbance are thought to be perceived as a source of risk analogous to predation risk in wildlife. As such, can alter behaviour and habitat use of foraging animals.

Urban wildlife faces increased exposure to human disturbance, meaning that they may face an increase in perceived risk during food acquisition. Urban habitats also include novel and altered food resources that could result in urban wildlife having to face distinct trade-offs associated with foraging and patch use compared to rural counterparts.

To examine how a relatively successful invasive urban mammal, the eastern grey squirrel, balances risk and safety under human disturbance, we measured giving-up densities (GUD) at artificial food patches placed at sites subject to varying levels of urbanisation to investigate how features associated with human disturbance might influence feeding decisions.

We found that differences in GUDs between ‘safe’ and risky’ patches were reduced closer to roads only under noisy conditions, suggesting that the risk of predation is perceived by squirrels as reduced when disturbance from human activities is highest. However, there was also a significant effect of the variability in noise levels on patterns of patch exploitation, with higher GUDs and larger GUD differences between safe and risky patches found under more variable noise levels, suggesting that squirrels might also find dynamic human disturbances startling or distracting while foraging.

Synthesis: Our results show how human activities can have doubled-edged impacts on the urban landscape of fear through offering reduced risk from predators whilst increasing foraging costs via noise disturbance. Future research could consider how foraging decisions in urban wildlife vary according to food supply and disturbance levels, to shed further light on foraging trade-offs made by wildlife under increasing urbanisation levels.
Lepidopteran scale cells derive from sensory organ precursors through a canonical lineage
Authors: Loh Ling S. , DeMarr Kyle A. , Tsimba Martina , Heryanto Christa , Berrio Alejandro , Patel Nipam H. , Martin Arnaud , McMillan W. Owen , Wray Gregory A. , Hanly Joseph J.
Published: June 2024

The success of butterflies and moths is tightly linked to the origin of scales within the group. A long-standing hypothesis postulates that scales are homologous to the well-described mechanosensory bristles found in the fruit flyDrosophila melanogaster, where both derive from an epithelial precursor specified by lateral inhibition that then undergoes multiple rounds of division. Previous histological examination and candidate gene approaches identified parallels in genes involved in scale and bristle development. Here, we provide definitive developmental and transcriptomic evidence that the differentiation of lepidopteran scales derives from the canonical cell lineage, known as the Sensory Organ Precursor (SOP). Live imaging in moth and butterfly pupae shows that SOP cells undergo two rounds of asymmetric divisions that first abrogate the neurogenic lineage, and then lead to a differentiated scale precursor and its associated socket cell. Single-nucleus RNA sequencing across a time-series of early pupal development revealed differential gene expression patterns that mirror canonical lineage development, including Notch-Delta signalling components, cell adhesion molecules, cell cycling factors, and terminal cell differentiation markers, suggesting a shared origin of the SOP developmental program. Additionally, we recovered a novel gene, the POU-domain transcription factorpdm3, involved in the proper differentiation of butterfly wing scales. Altogether, these data open up avenues for understanding scale type specification and development, and illustrate how single-cell transcriptomics provide a powerful platform for understanding the evolution of cell types.
Some like it hot: efficiency of the type III secretion system and activation of plant defenses have multiple thermosensitive behaviors in thePseudomonas syringaecomplex
Authors: Caullireau E. , Danzi D. , Tempo V.M. , Pandolfo M. , Morris C.E. , Vandelle E.
Published: June 2024

ThePseudomonas syringaespecies complex is a very important plant pathogenic bacterium, causing damage and economic losses on many crops. Research efforts for the understanding of the determinants of the host-range of a given strain are considerable. Recently, we showed that the inability of aP. syringaepv.actinidiaestrain to trigger ETI inA. thalianais due to an inefficient T3SS and not to the absence of a recognized effector. In this context, we compared severalP. syringaestrains belonging to different phylogroups and carrying the same plasmid-born avirulence gene for their ability to induce an HR inA. thalianaCol-0, as a marker of T3SS efficiency.PtoDC3000AvrBandPmaM6AvrBconsistently triggered a strong HR while other strains induced it at different intensities significantly depending on temperature. Both behaviors of low and warm temperature-dependency for T3SS efficiency were observed among thermosensitive strains, irrespective of theirin-vitrogrowth optimum. Surprisingly, differences were also observed among quasi-clonal strains. These results reveal a strongly strain-specific regulatory role of temperature in effector injection and reinforce the notion that the presence/absence of effectors is not sufficient to predict the outcome of plant-bacteria interactions. Moreover, this work highlights the necessity to study bacterial virulence in a broader set of strains insofar asPtoDC3000 is a reliable model strain but not representative of theP. syringaecomplex.

Author summary

Pseudomonas syringaeis a bacterium ubiquitous in the environment and responsible for important crop losses worldwide. Moreover,P. syringaeserves as a model organism for studying plant-pathogen interactions. Bacteria rely on various virulence mechanisms to successfully infect their host, one of the most important of which is the Type III Secretion System (T3SS). Although it is acknowledged that environmental conditions play a significant role in the plant-pathogen interactions, our understanding of their influence on both partners is still limited. Regarding temperature, contrasting findings have been reported about its influence on T3SS efficiency. While most efforts have focused on a few strains ofP. syringae, the phylogenetic diversity of this bacterium is enormous. Consequently, we decided to characterize the role of temperature on T3SS efficiency inP. syringaein a broader way. Our results showed that bacterial behavior in response to temperature is highly variable among strains, even among very closely related ones. Our study provides new insights into the role of temperature in regulating bacterial virulence and further evidence of the need to investigate the diversity of pathogenic organisms beyond model strains.
Decomposed Linear Dynamical Systems (dLDS) models reveal context-dependent dynamic connectivity inC. elegans
Authors: Yezerets Eva , Mudrik Noga , Charles Adam S.
Published: June 2024

Despite innumerable efforts to characterizeC. elegansneural activity and behavior, the roles of each individual neuron and the compositional mechanisms of all their interactions are still not completely known. In particular, there is evidence thatC. elegansneurons perform changing roles over time, in different behavioral contexts, etc.; however, existing stationary anatomical and functional connectivity can average across time and obfuscate the nonstationary nature of the neural dynamics. We contribute to these efforts by leveraging recent advances in decomposed linear dynamical systems (dLDS) models. dLDS models neural dynamics in a latent space with a set of linear operators that can be recombined and reused over time, enabling the discovery of multiple parallel neural processes on different timescales. We leverage the ability to identify reused patterns of dynamical neural interactions, which we call “dynamical connectivity,” to 1) identify contextually dependent roles of neurons; 2) discover the underlying variability of neural representations even under discrete behaviors; 3) quantify differences between anatomical, functional, and dynamical connectivity; and 4) learn a single aligned latent space underlying multiple individual worms’ activity. These results highlight the importance of defining a neuron’s functions not solely by its internal activity or place in a time-averaged network, but by its evolving interactions across context-dependent circuits.
Real-World Effectiveness of Deltamethrin-Clothianidin (FLUDORA FUSION) in Indoor Residual Spraying in Sub-Saharan Africa: A Systematic Review Protocol
Authors: Ocan Moses , Loyce Nakalembe , Ojiambo Kevin Ouma , Kinalwa Geofrey , Kinengyere Alison A. , Nsobya Sam , Arinaitwe Emmanuel , Mawejje Henry
Published: June 2024

Background

Indoor residual spraying (IRS) is a core insecticide-based vector control tool employed in most malaria-affected settings globally. However, mosquito vectors have developed resistance to nearly all the insecticides currently used in IRS. This has necessitated a transition to new classes of insecticides from mostly using Dichlorodiphenyltrichloroethane (DDT) and pyrethroids from 1997 to 2010, to carbamates from 2011 and organophosphates from 2013. In addition, other vector control measures like the use of long-lasting insecticide-treated bed nets (LLINs) have also been employed for malaria control. Despite the implementation of these mosquito vector control interventions, malaria remains a disease of public health concern especially in sub-Saharan Africa which bears over 90% of the disease burden. This review will thus collate evidence on the effectiveness of IRS for malaria control in sub-Saharan Africa.

Methods and analysis

The systematic review will be done followinga prioricriteria developed using PRISMA guidelines. Articles will be obtained through a search of Medline via PubMed, Scopus, and Embase databases. The Mesh terms and Boolean operators (“AND,” “OR”) will be used in the article search. Additionally, websites of malaria research institutions will be searched. Article search will be done by two independent librarians (AAK and RS). All identified articles will be transferred to Epi-reviewer v6.15.1.0 software. Article screening and data abstraction will be done in duplicate by four reviewers (KO, LN, GK and MO) and any further disagreements will be resolved through discussion and consensus. Data analysis will be done using STATAv17.0. Heterogeneity in the articles will be assessed using the I2statistic. Publication bias will be assessed using a funnel plot.

Results

The findings of this review will help generate evidence on the effectiveness of indoor residual spraying using WHO pre-qualified insecticides in malaria control in sub-Saharan Africa.

This protocol was registered in PROSPERO (https://www.crd.york.ac.uk/prospero/) registration number CRD42024517119
A melancholy machine: simulated synapse loss induces depression-like behaviors in deep reinforcement learning
Authors: Chalmers Eric , Duarte Santina , Al-Hejji Xena , Devoe Daniel , Gruber Aaron , McDonald Robert
Published: June 2024

Deep Reinforcement Learning is a branch of artificial intelligence that uses artificial neural networks to model reward-based learning as it occurs in biological agents. Here we modify a Deep Reinforcement Learning approach by imposing a suppressive effect on the connections between neurons in the artificial network - simulating the effect of dendritic spine loss as observed in major depressive disorder (MDD). Surprisingly, this simulated spine loss is sufficient to induce a variety of MDD-like behaviors in the artificially intelligent agent, including anhedonia, increased temporal discounting, avoidance, and an altered exploration/exploitation balance. Furthermore, simulating alternative and longstanding reward-processing-centric conceptions of MDD (dysfunction of the dopamine system, altered reward discounting, context-dependent learning rates, increased exploration) does not produce the same range of MDD-like behaviors. These results support a conceptual model of MDD as a reduction of brain connectivity (and thus information-processing capacity) rather than an imbalance in monoamines - though the computational model suggests a possible explanation for the dysfunction of dopamine systems in MDD. Reversing the spine-loss effect in our computational MDD model can lead to rescue of rewarding behavior under some conditions. This supports the search for treatments that increase plasticity and synaptogenesis, and the model suggests some implications for their effective administration.

Significance statement

Simulating dendritic spine loss in a deep reinforcement learning agent causes the agent to exhibit a surprising range of depression-like behaviors. Simulating spine restoration allows rewarding behavior to be re-learned. This computational model sees Major Depressive Disorder as a reversible loss of brain capacity, providing some insights on pathology and treatment.
Sex Differences in Morphine Sensitivity of Neuroligin-3 Knockout Mice
Authors: Brandner Dieter D. , Mashal Mohammed A. , Grissom Nicola M. , Rothwell Patrick E.
Published: June 2024

Sex has a strong influence on the prevalence and course of brain conditions, including autism spectrum disorders. The mechanistic basis for these sex differences remains poorly understood, due in part to historical bias in biomedical research favoring analysis of male subjects, and the exclusion of female subjects. For example, studies of male mice carrying autism-associated mutations in neuroligin-3 are over-represented in the literature, including our own prior work showing diminished responses to chronic morphine exposure in male neuroligin-3 knockout mice. We therefore studied how constitutive and conditional genetic knockout of neuroligin-3 affects morphine sensitivity of female mice. In contrast to male mice, female neuroligin-3 knockout mice showed normal psychomotor sensitization after chronic morphine exposure. However, in the absence of neuroligin-3 expression, both female and male mice show a similar change in the topography of locomotor stimulation produced by morphine. Conditional genetic deletion of neuroligin-3 from dopamine neurons increased the locomotor response of female mice to high doses of morphine, contrasting with the decrease in psychomotor sensitization caused by the same manipulation in male mice. Together, our data reveal that knockout of neuroligin-3 has both common and distinct effects on morphine sensitivity in female and male mice. These results also support the notion that female sex can confer resilience against the impact of autism-associated gene variants.
Endocytic adaptor AP-2 maintains Purkinje cell function by balancing cerebellar parallel and climbing fiber synapses
Authors: Tolve M. , Tutas J. , Özer- Yildiz E. , Klein I. , Koletsu E , Petzold A. , Liebsch F. , Silverman Q. , Overhoff M. , Schwarz G. , Korotkova T. , Valtcheva S. , Gatto G. , Kononenko NL
Published: June 2024

The selective loss of cerebellar Purkinje cells is a hallmark of various neurodegenerative movement disorders, yet the precise mechanism driving their degeneration remains enigmatic. Here, we show that the endocytic adaptor protein complex 2 (AP-2) is essential for the survival of Purkinje cells. Employing a multidisciplinary approach encompassing mouse genetics, viral tracing, ex vivo calcium imaging, and kinematic analysis, we demonstrate that mice lacking the µ-subunit of AP-2 in cerebellar Purkinje cells exhibit early-onset ataxia associated with progressive Purkinje cell degeneration. Importantly, we uncover that synaptic input dysfunctions, characterized by a predominance of parallel fiber (PF) over climbing fiber (CF) synapses, precede Purkinje cell loss. Mechanistically, we find that AP-2 localizes to Purkinje cell dendrites, where it interacts with the PF synapse-enriched protein GRID2IP. The loss of AP-2 results in proteasome-dependent degradation of GRID2IP and accumulation of the glutamate δ2 receptor (GLURδ2) in distal Purkinje cell dendrites, leading to an excess of PF synapses while CF synapses are drastically reduced. The overrepresentation of PF synaptic input induces Purkinje cell hyperexcitation, which can be alleviated by enhancing synaptic glutamate clearance using the antibiotic ceftriaxone. Our findings demonstrate the critical role of AP-2 in preventing motor gait dysfunctions by regulating GRID2IP levels in Purkinje cells, thereby preserving the equilibrium of PF and CF synaptic inputs in a cell-autonomous manner.
Optogenetic inhibition of light-captured alcohol-taking striatal engrams facilitates extinction and suppresses reinstatement
Authors: Vierkant Valerie , Xie Xueyi , Huang Zhenbo , He Lian , Bancroft Eric , Wang Xuehua , Srinivisan Rahul , Zhou Yubin , Wang Jun
Published: June 2024

Background

Alcohol use disorder (AUD) is a complex condition, and it remains unclear which specific neuronal substrates mediate alcohol-seeking and -taking behaviors. Engram cells and their related ensembles, which encode learning and memory, may play a role in this process. We aimed to assess the precise neural substrates underlying alcohol-seeking and -taking behaviors and determine how they may affect one another.

Methods

Using FLiCRE (Fast Light and Calcium-Regulated Expression; a newly developed technique which permits the trapping of acutely activated neuronal ensembles) and operant-self administration (OSA), we tagged striatal neurons activated during alcohol-taking behaviors. We used FLiCRE to express an inhibitory halorhodopsin in alcohol-taking neurons, permitting loss-of-function manipulations.

Results

We found that the inhibition of OSA-tagged alcohol-taking neurons decreased both alcohol-seeking and -taking behaviors in future OSA trials. In addition, optogenetic inhibition of these OSA-tagged alcohol-taking neurons during extinction training facilitated the extinction of alcohol-seeking behaviors. Furthermore, inhibition of these OSA-tagged alcohol-taking neurons suppressed the reinstatement of alcohol-seeking behaviors, but, interestingly, it did not significantly suppress alcohol-taking behaviors during reinstatement.

Conclusions

Our findings suggest that alcohol-taking neurons are crucial for future alcohol-seeking behaviors during extinction and reinstatement. These results may help in the development of new therapeutic approaches to enhance extinction and suppress relapse in individuals with AUD.
Generalized cue reactivity in dopamine neurons after opioids
Authors: Lehmann Collin M. , Miller Nora E. , Nair Varun S. , Costa Kauê M. , Schoenbaum Geoffrey , Moussawi Khaled
Published: June 2024

Cue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues and is a major driver of relapse. The leading hypothesis is that dopamine release by addictive drugs represents a persistently positive reward prediction error that causes runaway enhancement of dopamine responses to drug cues, leading to their pathological overvaluation compared to non-drug reward alternatives. However, this hypothesis has not been directly tested. Here we developed Pavlovian and operant procedures to measure firing responses, within the same dopamine neurons, to drug versus natural reward cues, which we found to be similarly enhanced compared to cues predicting natural rewards in drug-naïve controls. This enhancement was associated with increased behavioral reactivity to the drug cue, suggesting that dopamine release is still critical to cue reactivity, albeit not as previously hypothesized. These results challenge the prevailing hypothesis of cue reactivity, warranting new models of dopaminergic function in drug addiction, and provide critical insights into the neurobiology of cue reactivity with potential implications for relapse prevention.
Stimulus-specificity of surround-induced responses in primary visual cortex
Authors: Cuevas Nisa , Sotomayor-Gómez Boris , Tzanou Athanasia , Broggini Ana , Uran Cem , Vinck Martin
Published: June 2024

Recent studies in mice challenge the traditional notion of the V1 receptive field (RF) showing increases in V1 firing rates for stimuli presented in the surround, in the absence of a visual input into the classical RF. While this effect has been interpreted as a prediction of the occluded content or a prediction error, an alternative explanation is that it reflects the representation of the uniform achromatic (gray) surface itself. To study this, we systematically investigated the dependence of V1 rate increases on the properties of distal surround stimuli. We recorded V1 and LGN neurons using Neuropixels in awake mice and demonstrated surround-induced responses in V1. That is, V1 firing rates increase by presenting a grating stimulus in the distal surround, while the RF is covered by a large gray patch up to 90° of diameter. LGN firing rates decreased for the same stimuli. V1 response latencies showed a systematic increase with the size of the gray patch. Surround-induced responses did not require spatial continuity or motion coherence of the surround stimulus and generalized to noisy textures and black/white luminance surfaces. Responses to black/white surfaces on a gray background had a similar magnitude and response latency as surround-induced responses with a black/white background. Based on these findings, we suggest that surround-induced responses primarily reflect the representation of the achromatic surface itself, which can contribute to image segmentation.
Protein Design with StructureGPT: a Deep Learning Model for Protein Structure-to-Sequence Translation
Authors: Zalba Nicanor , Ursua-Medrano Pablo , Bustince Humberto
Published: June 2024

Motivation: Protein design, crucial for understanding and engineering protein functionalities, has traditionally been challenged by the reverse translation of complex protein tertiary structures into sequences. Existing computational tools have focused predominantly on sequence-to-structure predictions, with less attention given to structure-to-sequence processes. Our research introduces StructureGPT, a novel deep learning model that employs advanced natural language processing techniques to translate complex protein tertiary structures into their corresponding amino acid sequences. This model addresses critical gaps in protein engineering, particularly improving solubility and stability, which are essential for pharmaceutical development and industrial applications. Results: StructureGPT demonstrates the capability to autoregressively generate amino acid sequences from detailed structural inputs, enhancing the design of proteins with specific functionalities. By leveraging the linguistic parallels between protein structures and human language, our model not only predicts sequences with high accuracy but also suggests modifications that could lead to improved protein properties. The application of StructureGPT in multiple protein design tasks showcases its utility in various biomedical and biotechnological contexts. Availability: The source code for StructureGPT is freely available at https://github.com/StructureGPT DOI: 10.5281/zenodo.11065607
Rearrangements and accelerated mutation rates on Dendrodorididae mitogenomes rumble their evolution
Authors: Galià-Camps Carles , Schell Tilman , Enguídanos Alba , Pegueroles Cinta , Arnedo Miquel , Ballesteros Manuel , Valdés Ángel , Greve Carola
Published: June 2024

The systematics of the family Dendrodorididae poses a challenge to evolutionary biologists, as their mitochondrial and nuclear markers provide contradictory phylogenetic signals. Nuclear pseudogenes or exogenous contamination are hypothesized to cause the molecular discordance. However, these hypotheses have not been tested. We used genomic data from seven Dendrodorididae species to investigate the evolution of this family. Two mitogenomes displayed a novel structural rearrangement in nudibranchs, involving the translocation of three collinear genes and five surrounding tRNAs. Additionally, we found numerous mitogenomic regions with non-synonymous mutations and multiple indels in both coding and ribosomal genes. Protein modeling resulted in similar structures, suggesting that functionality is conserved. Phylogenies using mitogenomic data confirmed a specific clade membership for the rearranged mitogenomes. The incorporation of nuclear data did not fully resolve the systematic relationships of Dendrodorididae, acknowledging the evolutionary complexity of this group. The present study provides novel evidence on sudden molecular changes in mitogenomes, and highlights the relevance of using genomic data to unveil rare evolutionary processes, which is critical for understanding evolution of neglected taxa.
Seasonal niche overlap of diverse facultative antagonistic bacteria of diatoms in a productive coastal ecosystem
Authors: Branscombe Laura , Roberts Cordelia , Widdicombe Claire , Swink Courtney , Wilson William H. , Cunliffe Michael , Helliwell Katherine
Published: June 2024

Biotic interactions between microbes underpin marine ecosystem health, governing the flux of carbon and other nutrients in the ocean. However, studying aquatic microbial interactions is challenging. Model systems can provide in depth understanding of the mechanisms driving such associations. Yet, insights of the prevalence and co-occurrence dynamics of laboratory model systems in natural ecosystems remain limited. By leveraging 16S and 18S metabarcoding combined with phylogenetic analysis, we assessed the environmental presence of facultative bacterial pathogens of one of the most globally abundant phytoplankton groups, the diatoms. Sampling microbial assemblages in a productive coastal ecosystem over the course of an annual cycle, we detected multiple algicidal bacteria that frequently exhibited overlapping co-occurrences. Together, these bacteria positively correlated with members of the potentially toxic genusPseudo-nitzchia, as well as temperature. Our study indicates that antagonistic bacteria occupy shared temporal niches and demonstrates the need to consider their cumulative impacts on diatom population health, including in future ocean conditions.