bluuebunny/crossref_metadata_2025 huggingface dataset:
Commensalibacter nepenthis sp. nov. and Commensalibacter oyaizuii sp. nov., from fluid in a Nepenthes pitcher cup and a butterfly (Junonia lemonias) in Thailand
Authors: Yukphan Pattaraporn , Charoenyingcharoen Piyanat , Muangham Supattra , Mhuantong Wuttichai , Yamada Yuzo
Published: May 2024

Two novel Gram-negative, aerobic, rod-shaped, non-motile bacteria, strains TBRC 10068T and TBRC 16381T, were isolated from a fluid sample from a close-pitcher cup (Nepenthes gracilis) and an insect sample (Junonia lemonias), respectively. Comparing the 16S rRNA gene sequences with those found in EzBioCloud’s publicly available databases revealed that the two strains exhibited a close genetic relationship with Commensalibacter intestini A911T; the calculated sequence similarities were 98.56 and 97.70  %, respectively. The average nucleotide identity and digital DNA–DNA hybridization values of the two Commensalibacter strains, as well as those of their closely related type strains, were found to be lower than the species demarcation threshold of 95 and 70 %, respectively. The phylogenomic analysis of strains TBRC 10068T and TBRC 16381T showed that they belong to the genus Commensalibacter. However, they formed distinct lineages separate from all other strains of Commensalibacter by use of 81 bacterial core genes. In addition, the comparative genomic analysis revealed that the core orthologues of strains TBRC 10068T and TBRC 16381T, compared to the closely related type strains of Commensalibacter species, had distinct genetic profiles. Strain TBRC 10068T contained 163 unique genes, whereas strain TBRC 16381T contained 83. The three Commensalibacter species possessed Q-9 as the primary isoprenoid quinone homologue. The results of a polyphasic taxonomic investigation indicated that strains TBRC 10068T and TBRC 16381T represent two separate new species within the genus Commensalibacter. The species were designated as Commensalibacter nepenthis sp. nov. with the type strain TBRC 10068T (=KCTC 92798T) and Commensalibacter oyaizuii sp. nov. with the type strain TBRC 16381T (=KCTC 92799T).
Microfluidic platform for microbial spore germination studies in multiple growth conditions
Authors: Bernier Léa S. , Estoppey Aislinn , Bindschedler Saskia , Stan Guy-Bart , Junier Pilar , Stanley Claire E.
Published: May 2024

Spores are highly resistant dormant cells, adapted for survival and dispersal, that can withstand unfavourable environmental conditions for extended periods of time and later reactivate. Understanding the germination process of microbial spores is important in numerous areas including agriculture, food safety and health, and other sectors of biotechnology. Microfluidics combined with high-resolution microscopy allows to study spore germination at the single-cell level, revealing behaviours that would be hidden in standard population-level studies. Here, we present a microfluidic platform for germination studies where spores are confined to monolayers inside microchambers, allowing the testing of four growth conditions in parallel. This platform can be used with multiple species, including non-model organisms, and is compatible with existing image analysis software. In this study, we focused on three soil dwellers, two prokaryotes and one fungus, and revealed new insights into their germination. We studied endospores of the model bacteriumBacillus subtilisand demonstrated a correlation between spore density and germination in rich media. We then investigated the germination of the obligate-oxalotrophic environmental bacteriumAmmoniphilus oxalaticusin a concentration gradient of potassium oxalate, showing that lower concentrations result in more spores germinating compared to higher concentrations. We also used this microfluidic platform to study the soil beneficial filamentous fungusTrichoderma rossicum, showing for the first time that the size of the spores and hyphae increase in response to increased nutrient availability, while germination times remain the same. Our platform allows to better understand microbial behaviour at the single-cell level, under a variety of controlled conditions.

One-Sentence Summary

A microfluidic platform developed for spore germination studies in multiple growth conditions provides new insights into the germination of spores at the cellular level from three soil dwellers.
Is the population of the Critically Endangered White-bellied Heron in Namdapha Tiger Reserve, India, declining?
Authors: Menzies Rohan K. , Suryawanshi Kulbhushansingh R. , Naniwadekar Rohit
Published: May 2024

The Critically Endangered White-bellied HeronArdea insignisis a large-bodied, range-restricted, piscivorous bird found in the Himalayan mountains. With fewer than 60 individuals remaining globally, regular monitoring efforts are required to understand the conservation status of this rare species better. Here, we present the results of river surveys from 2017 and 2023-24 for the White-bellied Heron in an important protected area, the Namdapha Tiger Reserve, in Arunachal Pradesh. The encounter rate in 2017 was 0.55 herons per km, however; we did not detect the bird during intensive river sampling in the same stretches in 2023-24. This area within the reserve was once a stronghold for the species and they currently appear to be declining or locally extinct. Given the declines within this Protected Area, the drivers for the same need to be determined. While repeated monitoring of rivers has helped reveal this decline, locating and conserving stretches of river utilised by the remaining individuals away from the core zone is now critical.

[Supplementary material for this article can be found at https://doi.org/xxx]
How many segments are enough to biomechanically model the feet? A comparison of inverse kinematics and dynamics in multisegmented foot models
Authors: Nicolescu Julia , Gaudette Logan , Vogel Olivia , Davis Irene S. , Tenforde Adam S. , Troy Karen L.
Published: May 2024

Multisegmented foot models (MSFMs) capture kinematic and kinetic data of specific regions of the foot instead of representing the foot as a single, rigid segment. Models differ by the number of segments and segment definitions, so there is no consensus for best practice. It is unknown whether MSFMs yield the same joint kinematic and kinetic data and what level of detail is necessary to accurately measure such values. We compared the angle, moment, and power measurements at the tibiotalar, midtarsal, and metatarsophalangeal joints of four MSFMs using motion capture data of young adult runners during stance phase of barefoot walking and jogging. Of these models, three were validated: Oxford Foot Model, Milwaukee Foot Model, and Ghent Foot Model. One model was developed based upon literature review of existing models: the “Vogel” model. We performed statistical parametric mapping comparing joint measurements from each model to the corresponding results from the Oxford Model, the most heavily studied MSFM. We found that the Oxford Foot Model, Milwaukee Foot Model, Vogel Foot Model, and Ghent Foot Model do not provide the same results. The changes in model segment definitions impact the degrees of freedom in ways that alter the measured kinematic function of the foot, which in turn impacts the kinetic results. We also found that dynamic function of the midfoot/arch may be better captured by MSFMs with a separate midfoot segment. The results of this study capture the variability in performance of MSFMs and indicate a need to standardize the design of MSFMs.
Loss-of-function of ALDH3B2 transdifferentiates human pancreatic duct cells into beta-like cells
Authors: Li Jian , Bode Kevin , Lee Yu-chi , Morrow Noelle , Ma Andy , Wei Siying , da Silva Pereira Jessica , Stewart Taylor , Lee-Papastavros Alexander , Hollister-Lock Jennifer , Sullivan Brooke , Bonner-Weir Susan , Yi Peng
Published: May 2024

Replenishment of pancreatic beta cells is a key to the cure for diabetes. Beta cells regeneration is achieved predominantly by self-replication especially in rodents, but it was also shown that pancreatic duct cells can transdifferentiate into beta cells. How pancreatic duct cells undergo transdifferentiated and whether we could manipulate the transdifferentiation to replenish beta cell mass is not well understood. Using a genome-wide CRISPR screen, we discovered that loss-of-function of ALDH3B2 is sufficient to transdifferentiate human pancreatic duct cells into functional beta-like cells. The transdifferentiated cells have significant increase in beta cell marker genes expression, secrete insulin in response to glucose, and reduce blood glucose when transplanted into diabetic mice. Our study identifies a novel gene that could potentially be targeted in human pancreatic duct cells to replenish beta cell mass for diabetes therapy.
Canalization and competition: the cornerstone of genetic network’s dynamic stability and evolution
Authors: Yao Yuxiang , Huang Zi-Gang , Pei Duanqing
Published: May 2024

Grasping the fundamental dynamic property is a crucial approach for understanding living systems. Here we conduct a comprehensive study into the relationship between regulatory modes and dynamic features of gene networks. Our findings indicate that conditional constraints and competition, corresponding to canalizing and threshold regulating modes respectively, play pivotal roles in driving gene networks towards criticality. Particularly, they effectively rescue biosystems from disordered area as source of evolutionary driving force. By employing variant Kauffman models, order parameters, and stability analysis, we provide sufficient numerical evidence demonstrating the diverse and distinctive capabilities of regulatory modes in stabilizing systems. Our findings give the most systematic analysis to date on the dynamic atlas of regulatory modes, offering a framework-independent proof of genetic networks operating at the edge of chaos with evolutionary implications. Furthermore, we discus the bridge between criticality and canalizing/threshold regulating modes and propose a reasonable scheme for generating model.
Predictive modeling of hematoma expansion from non-contrast computed tomography in spontaneous intracerebral hemorrhage patients
Authors: Ironside Natasha , El Naamani Kareem , Rizvi Tanvir , E-Rabbi Mohammed Shifat , Kundu Shinjini , Becceril-Gaitan Andrea , Pas Kristofor , Snyder Harrison , Chen Ching-Jen , Langefeld Carl D. , Woo Daniel , Mayer Stephan , Connolly E. Sander , Rohde Gustavo
Published: May 2024

Hematoma expansion is a consistent predictor of poor neurological outcome and mortality after spontaneous intracerebral hemorrhage (ICH). An incomplete understanding of its biophysiology has limited early preventative intervention. Transport-based morphometry (TBM) is a mathematical modeling technique that uses a physically meaningful metric to quantify and visualize discriminating image features that are not readily perceptible to the human eye. We hypothesized that TBM could discover relationships between hematoma morphology on initial Non-Contrast Computed Tomography (NCCT) and hematoma expansion. 170 spontaneous ICH patients enrolled in the multi-center international Virtual International Trials of Stroke Archive (VISTA-ICH) with time-series NCCT data were used for model derivation. Its performance was assessed on a test dataset of 170 patients from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. A unique transport-based representation was produced from each presentation NCCT hematoma image to identify morphological features of expansion. The principal hematoma features identified by TBM were larger size, density heterogeneity, shape irregularity and peripheral density distribution. These were consistent with clinician-identified features of hematoma expansion, corroborating the hypothesis that morphological characteristics of the hematoma promote future growth. Incorporating these traits into a v achieved a AUROC of 0.71 for quantifying 24-hour hematoma expansion risk in the test dataset. This outperformed existing clinician protocols and alternate machine learning methods, suggesting that TBM detected features with improved precision than by visual inspection alone. This pre-clinical study presents a quantitative and interpretable method for discovery and visualization of NCCT biomarkers of hematoma expansion in ICH patients. Because TBM has a direct physical meaning, its modeling of NCCT hematoma features can inform hypotheses for hematoma expansion mechanisms. It has potential future application as a clinical risk stratification tool.
Optimal timing of booster doses in a highly vaccinated population with minimal natural exposure to COVID-19
Authors: Conway Eamon , Walker Camelia , Lydeamore Michael , Golding Nick , Ryan Gerard , Mavec Dario , Oates James , Kabashima Greg , Price David J , Shearer Freya , Cromer Deborah , Davenport Miles P , McCaw James , Eriksson Emily M , Hodgkin Philip D , Wu Logan , Le Thao P. , Baker Christopher M. , Mueller Ivo , McVernon Jodie
Published: May 2024

Population-level waning of protection following immunising exposures is an important determinant of susceptibility to COVID-19 outbreaks. This work outlines an individual-based model (IBM) for the transmission and clinical impact of SARS-CoV-2 that explicitly represents the immunological response to vaccination and infection of each individual. The IBM evaluates waning of immunity to inform risk of infection and related clinical outcomes across a large freely mixing population over time by age and prior exposure status. Modelling immunological responses allows us to investigate the likely impact of immune escape variants based on the landscape in which they emerge. The model described in this paper was motivated by the need to anticipate health and societal impacts of COVID-19 in Australia following emergence of the Omicron variant, in the context of high national vaccine uptake but low infection exposure. It provides a flexible framework for modelling policy-relevant scenarios to inform preparedness and response actions as immunity in a population changes through time.
Cramming Protein Language Model Training in 24 GPU Hours
Authors: Frey Nathan C. , Joren Taylor , Ismail Aya Abdelsalam , Goodman Allen , Bonneau Richard , Cho Kyunghyun , Gligorijević Vladimir
Published: May 2024

Protein language models (pLMs) are ubiquitous across biological machine learning research, but state-of-the-art models like ESM2 take hundreds of thousands of GPU hours to pre-train on the vast protein universe. Resource requirements for scaling up pLMs prevent fundamental investigations into how optimal modeling choices might differ from those used in natural language. Here, we define a “cramming” challenge for pLMs and train performant models in 24 hours on a single GPU. By re-examining many aspects of pLM training, we are able to train a 67 million parameter model in a single day that achieves comparable performance on downstream protein fitness landscape inference tasks to ESM-3B, a model trained for over 15, 000×more GPU hours than ours. We open source our library1for training and inference,LBSTER:Language models forBiologicalSequenceTransformation andEvolutionaryRepresentation.
The 18S rRNA Methyltransferase DIMT-1 Regulates Lifespan in the Germline Later in Life
Authors: Rothi M. Hafiz , Sarkar Gautam Chandra , Haddad Joseph Al , Mitchell Wayne , Ying Kejun , Pohl Nancy , Sotomayor-Mena Roberto G. , Natale Julia , Dellacono Scarlett , Gladyshev Vadim N. , Greer Eric Lieberman
Published: May 2024

Ribosome heterogeneity has emerged as an important regulatory control feature for determining which proteins are synthesized, however, the influence of age on ribosome heterogeneity is not fully understood. Whether mRNA transcripts are selectively translated in young versus old cells and whether dysregulation of this process drives organismal aging is unknown. Here we examined the role of ribosomal RNA (rRNA) methylation in maintaining appropriate translation as organisms age. In a directed RNAi screen, we identified the 18S rRNA N6’-dimethyl adenosine (m6,2A) methyltransferase,dimt-1,as a regulator ofC. eleganslifespan and stress resistance. Lifespan extension induced bydimt-1deficiency required a functional germline and was dependent on the known regulator of protein translation, the Rag GTPase,raga- 1,which links amino acid sensing to the mechanistic target of rapamycin complex (mTORC)1. Using an auxin-inducible degron tagged version ofdimt-1,we demonstrate that DIMT-1 functions in the germline after mid-life to regulate lifespan. We further found that knock-down ofdimt-1leads to selective translation of transcripts important for stress resistance and lifespan regulation in theC. elegansgermline in mid-life including the cytochrome P450daf-9,which synthesizes a steroid that signals from the germline to the soma to regulate lifespan. We found thatdimt-1induced lifespan extension was dependent on thedaf-9signaling pathway. This finding reveals a new layer of proteome dysfunction, beyond protein synthesis and degradation, as an important regulator of aging. Our findings highlight a new role for ribosome heterogeneity, and specific rRNA modifications, in maintaining appropriate translation later in life to promote healthy aging.
Benefits of spaced learning are predicted by re-encoding of past experience in ventromedial prefrontal cortex
Authors: Zou Futing , Kuhl Brice A. , DuBrow Sarah , Hutchinson J. Benjamin
Published: May 2024

More than a century of research shows that spaced learning improves long-term memory. Yet, there remains debate concerning why. A major limitation to resolving theoretical debates is the lack of evidence for how neural representations change as a function of spacing. Here, leveraging a massive-scale 7T human fMRI dataset, we tracked neural representations and behavioral expressions of memory as participants viewed thousands of natural scene images that repeated at lags ranging from seconds to many months. We show that spaced learning increases the similarity of human ventromedial prefrontal cortex representations across stimulus encounters and, critically, these increases parallel and predict the behavioral benefits of spacing. Additionally, we show that these spacing benefits critically depend on remembering and, in turn, ‘re-encoding’ past experience. Collectively, our findings provide fundamental insight into how spaced learning influences neural representations and why spacing is beneficial.
Organomics: A concept reflecting the importance of PET/CT healthy organ radiomics in non-small cell lung cancer prognosis prediction using machine learning
Authors: Salimi Yazdan , Hajianfar Ghasem , Mansouri Zahra , Sanaat Amirhosein , Amini Mehdi , Shiri Isaac , Zaidi Habib
Published: May 2024

Purpose

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer. Patient survival prediction using machine learning and radiomics analysis proved to provide promising outcomes. However, most studies reported in the literature focused on information extracted from malignant lesions. This study aims to explore the relevance and additional value of information extracted from healthy organs in addition to tumoral tissue using machine learning algorithms.

Methods

This study included PET/CT images of 154 patients collected from available online databases. The gross tumour volume (GTV) and 33 volumes of interest defined on healthy organs were segmented using nnU-Net deep learning-based segmentation. Subsequently, 107 radiomic features were extracted from PET and CT images (Organomics). Clinical information was combined with PET and CT radiomics from organs and GTVs considering 19 different combinations of inputs. Finally, different feature selection (FS, 5 methods) and machine learning (ML, 6 algorithms) algorithms were tested in a three-fold data split cross-validation scheme. The performance of the models was quantified in terms of the concordance index (C-index) metric.

Results

For an input combination of all radiomics information, most of the selected features belonged to PET Organomics and CT Organomics. The highest C-Index (0.68) was achieved using univariate C-Index FS method and random survival forest ML model using CT Organomics + PET Organomics as input as well as minimum depth FS method and CoxPH ML model using PET Organomics as input. Considering all 17 combinations with C-Index higher than 0.65, Organomics from PET or CT images were used as input in 16 of them.

Conclusion

The selected features and C-Indices demonstrated that the additional information extracted from healthy organs of both PET and CT imaging modalities improved the machine learning performance. Organomics could be a step toward exploiting the whole information available from multimodality medical images, contributing to the emerging field of digital twins in healthcare.
Managing Low Back Pain in Rural Uganda: A Qualitative Study Exploring the Perspectives and Practices of Frontline Health Workers regarding LBP Management in Primary Care
Authors: Harscouët Paul , Ndekezi Chimpaye Gloria , Kazibwe Herman , Kabakeynga Jerome , O’Callaghan Denise , Blake Catherine , Caulfield Brian , O’Sullivan Cliona
Published: May 2024

BACKGROUND AND AIMS

Low-back pain (LBP) is the main cause of years lived with disabilities (YLDs) worldwide and the second cause of YLDs in Uganda. In 2019, it was responsible for 7.4% of global YLDs and 5% of YLDs in Uganda. LBP takes a significant toll on people’s quality of life and disproportionately affects lower socioeconomic classes, elders, and women. In rural Uganda, LBP is managed in health centres by clinical officers and nurses with limited resources. This study aims to understand the perspectives and practices of these health workers.

Method

A qualitative design using semi-structured focus-group discussions was employed. Purposive sampling allowed us to identify relevant participants based on their roles as healthcare professionals working in primary care context in rural South-West Uganda. Data was analysed using thematic analysis.

Findings

LBP is a common and persistent complaint among patients presenting to rural health centres in Uganda. Manual labour and female specific health conditions were deemed to be common causes. There was a strong reliance on medication prescription, coupled with X-ray diagnosis, with little emphasis on education or exercise. Finally, findings highlighted major barriers for patients within the referral system to hospital care or rehabilitation.

Discussion

Education and training of frontline clinicians in terms of appropriate prescribing and rehabilitation for LBP is crucial. Evidence-based rehabilitation interventions need to be developed and adapted so that they can be delivered within the time and resource constraints of the health workforce, ensuring that they are acceptable and effective to patients in the context of rural Uganda.
Radiomic based investigation of a potential link between precuneus and fusiform gyrus with Alzheimer’s disease
Authors: Sharma Simran , Kundal Kavita , Chandok Ishsirjan Kaur , Kumar Neeraj , Kumar Rahul
Published: May 2024

Alzheimer’s disease (AD) is acknowledged as one of the most common types of dementia. Various brain regions were found to associated with AD pathology. Precuneus and fusiform gyrus are two notable regions whose role has been implicated in cognitive function. However, a thorough investigation was lacking to link these regions with AD pathology. In this study, we conducted a comprehensive radiomic based investigation using magnetic resonance imaging (MRI) scans to link precuneus and fusiform gyrus with AD pathology. We obtained T1 weighted MR scans of AD (n=133), MCI (n=311) and CN (n=195) subjects from ADNI database at three different time points (i.e., 0, 6 and 12 months). Then, we conducted statistical analysis to compare these features among AD, MCI and CN subjects. We found significant decline in gray matter volume (GMV) and cortical thickness of both precuneus and fusiform gyrus in AD as compared to the MCI and CN subjects. Further, we utilized these features to develop machine learning classifiers to classify AD from MCI and CN subjects and achieved accuracy of 97.78% and 94.41% respectively. These results strengthen the connection of precuneus and fusiform gyrus with AD pathology and opens a new avenue of AD research.
Effect of time restricted eating versus daily calorie restriction on sex hormones in males and females with obesity
Authors: Lin Shuhao , Cienfuegos Sofia , Ezpeleta Mark , Pavlou Vasiliki , Runchey Mary-Claire , Varady Krista A.
Published: May 2024

This study examined the effects of time restricted eating (TRE) on sex hormones in males and females, versus daily calorie restriction (CR). Adults with obesity (n = 90) were randomized to 1 of 3 groups for 12-months: 8-h TRE (eating only between 12:00 to 8:00 pm, with no calorie counting); CR (25% energy restriction daily); or control. Body weight decreased (P < 0.01) in the TRE and CR groups, relative to controls, in males, premenopausal females, and postmenopausal females, by month 12. Total testosterone, dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG) levels did not change over time, or between groups, in males, premenopausal females, and postmenopausal females. Estradiol, estrone, and progesterone were only measured in postmenopausal females, and remained unchanged. These findings suggest that TRE produces significant weight loss but does not impact circulating sex hormone levels in males and females with obesity over 12 months, relative to CR and controls.

Trial registration

Clinicaltrials.gov,NCT04692532.
Errors of attention adaptively warp spatial cognition
Authors: Brissenden James A. , Yin Yitong , Vesia Michael , Lee Taraz G.
Published: May 2024

Adaptation is the process by which we adjust internal models of the body, world, and mind in response to sensory feedback. While adaptation is studied extensively in the context of motor control, there is limited evidence that cognitive functions such as working memory are subject to the same error-driven adaptive control mechanism. To examine the possibility that internal spatial representations undergo adaptation, we had participants perform a task that interleaved a perceptual discrimination task and a spatial working memory task. Perceptual discrimination trials (85% of trials) presented an initial peripheral cue to exogenously capture attention, immediately followed by a displaced target stimulus. This sequence of events served to repeatedly induce a covert attentional allocation error. Interleaved spatial working memory trials (15% of trials) presented a stimulus at a pseudorandom peripheral location followed by a delay interval. On half of the working memory trials, the stimulus was surreptitiously presented at the same location as the initial attentional cue. We found that as attentional errors accumulated over the course of the experiment, participants’ spatial recall shifted to counteract the attentional error. The magnitude of this shift was proportional to the number of induced errors. Recall performance rapidly recovered following the offset of error trials. Multiple control experiments ruled out alternative explanations for these results, such as oculomotor confounds and attentional biases unrelated to error. These findings indicate that the computational mechanisms governing the adaptation of motor commands appear to similarly serve to adjust and calibrate spatial cognition.
Test–Retest Reliability of Meta Analytic Networks During Naturalistic Viewing
Authors: Kröll Jean-Philippe , Friedrich Patrick , Li Xuan , Nurislamova Yulia , Kraljevic Nevena , Geiger Anna , Mans Julia , Waite Laura , Caspers Julian , Qian Xing , Chee Michael WL , Zhou Juan Helen , Eickhoff Simon , Weis Susanne
Published: May 2024

Functional connectivity analyses have given considerable insights into human brain function and organization. As research moves towards clinical application, test-retest reliability has become a main focus of the field. So far, the majority of studies have relied on resting-state paradigms to examine brain connectivity, based on its low demand and ease of implementation. However, the reliability of resting-state measures is mostly moderate, potentially due to its unconstrained nature. Recently, naturalistic viewing paradigms have gained popularity because they probe the human brain under more ecologically valid conditions, thereby possibly increasing reliability. Therefore, we here compared the reliability of graph metrics extracted from resting-state and naturalistic viewing in functional networks, across two sessions. We show that naturalistic viewing can increase reliability over resting-state, but that its effect varies between stimuli and networks. Furthermore, we demonstrate that the effect of naturalistic viewing differs between two cohorts with Asian and European cultural backgrounds. Taken together, our study encourages the use of naturalistic viewing to increase reliability, but emphasizes the need to carefully select the appropriate stimulus and network for the respective research question.
Linking heartbeats with the cortical network dynamics involved in self-social touch distinction
Authors: Candia-Rivera Diego , de Vico Fallani Fabrizio , Boehme Rebecca , Salamone Paula C.
Published: May 2024

Research on interoception has revealed the role of heartbeats in shaping our perceptual awareness and embodying a first-person perspective. These heartbeat dynamics exhibit distinct responses to various types of touch. We advanced that those dynamics are directly associated to the brain activity that allows self-other distinction. In our study encompassing self and social touch, we employed a method to quantify the distinct couplings of temporal patterns in cardiac sympathetic and parasympathetic activities with brain connectivity. Our findings revealed that social touch led to an increase in the coupling between frontoparietal networks and parasympathetic/vagal activity, particularly in alpha and gamma bands. Conversely, as social touch progressed, we observed a decrease in the coupling between brain networks and sympathetic dynamics across a broad frequency range. These results show how heartbeat dynamics are intertwined with brain organization and provide fresh evidence on the neurophysiological mechanisms of self-social touch distinction.
Concurrent predictive and prospective strategies in a simple visuomotor task
Authors: Márquez Inmaculada , Treviño Mario
Published: May 2024

Interception, a fundamental visuomotor skill for activities such as driving and sports, involves two main strategies: predictive, anticipating the target’s trajectory, and prospective, actively tracking and adjusting movement. Experimentally controlled factors could potentially influence the relative usage of these strategies. We designed a visuomotor task to probe the relationship between target predictability and interception strategies. We manipulated stimulus predictability through controlled adjustments of external forces, altering the target’s trajectory. We also manipulated the availability of perceptual information by introducing spatial occlusion at specific parts of the visual field. Our observations indicate that decreased target variability promoted predictive interception, whereas increased variability prompted a shift toward prospective strategies. Notably, hand-catching trajectories exhibited increased curvature in response to changes in target variability, whereas eye trajectories displayed a relatively consistent curvature across trials. Similarly, heightened target variability resulted in delayed onset of hand movements while showing no discernible alterations in the onset of eye movements. Thus, gaze position was a poor predictor of hand position, highlighting distinct adaptive patterns for hand and eye movements in response to task unpredictability. Finally, participants exhibited consistent interception strategies within and across sessions, highlighting their differences and preferences for predictive or prospective strategies. These results reveal a dynamic interplay between target predictability and interception, suggesting a flexible combination of both approaches. Examining how humans integrate sensory information, plan, and execute movements provides a unique opportunity to characterize predictive and prospective interception strategies in dynamic, real-world scenarios.
Hematopoietic growth factors Regulate Entry of Monocytes into the Adult Brain via Chemokine Receptor CCR5
Authors: Ren Xuefang , He Junchi , Hu Heng , Kohsaka Shinichi , Zhao Li-Ru
Published: May 2024

Monocytes are circulating macrophage precursors and are generated from bone marrow hematopoietic stem cells. In the adults, monocytes continuously replenish cerebral border-associated macrophages under a physiological condition. Monocytes also rapidly infiltrate into the brain in the settings of pathological conditions. The mechanisms of recruiting monocyte-derived macrophages into the brain under pathological conditions have been extensively studied. However, it remains unclear how monocytes enter the brain for renewal of border-associated macrophages under the physiological condition. Using bothin vitroandin vivoapproaches, this study reveals that the combination of two hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF), complementarily and synergistically enhances adhesion of monocytes to cerebral endothelial cells in a dose dependent manner. Cysteine-cysteine chemokine receptor 5 (CCR5) in brain endothelial cells, but not cell adhesion molecules mediating neuroinflammation-related infiltration of monocyte-derived macrophages, modulates the SCF+G-CSF-enhanced monocyte-endothelial cell adhesion. Blocking CCR5 or genetically deleting CCR5 reduces monocyte-endothelial cell adhesion induced by SCF+G-CSF. SCF+G-CSF-enhanced recruitment of bone marrow-derived monocytes/macrophages in cerebral perivascular space is also reduced in adult CCR5 knockout mice. This study demonstrates the contribution of SCF and G-CSF in regulating the entry of monocytes into the adult brain to replenish perivascular macrophages.
MEA-seqX: High-resolution Profiling of Large-scale Electrophysiological and Transcriptional Network Dynamics
Authors: Emery Brett Addison , Hu Xin , Klütsch Diana , Khanzada Shahrukh , Larsson Ludvig , Dumitru Ionut , Frisén Jonas , Lundeberg Joakim , Kempermann Gerd , Amin Hayder
Published: May 2024

Concepts of brain function imply congruence and mutual causal influence between molecular events and neuronal activity. Decoding entangled information from concurrent molecular and electrophysiological network events demands innovative methodology bridging scales and modalities. Our MEA-seqX platform, integrating high-density microelectrode arrays, spatial transcriptomics, optical imaging, and advanced computational strategies, enables the simultaneous recording and analysis of molecular and electrical network activities at the level of individual cells. Applied to a mouse hippocampal model of experience-dependent plasticity, MEA-seqX unveiled massively enhanced nested dynamics between transcription and function. Graph-theoretic analysis revealed an increase in densely connected bimodal hubs, marking the first observation of coordinated spatiotemporal dynamics in hippocampal circuitry at both molecular and functional levels. This platform also identified different cell types based on their distinct bimodal profiles. Machine-learning algorithms accurately predicted network-wide electrophysiological features from spatial gene expression, demonstrating a previously inaccessible convergence across modalities, time, and scales.
An anesthetized rat assay for evaluating the effects of organophosphate-based compounds and countermeasures on intracranial EEG and respiratory rate
Authors: Thinschmidt J.S. , Talton J.D. , Harden S.W. , Frazier C.J.
Published: May 2024

The development of medical countermeasures (MCMs) against organophosphate (OP) induced poisoning is of substantial importance. Use of conventional therapeutics is complicated by off-target effects and restricted penetration of the blood-brain barrier (BBB). Therefore, a concerted effort is underway to discover improved acetylcholinesterase (AChE) reactivators, muscarinic acetylcholine receptor (mAChR) antagonists, and other countermeasures with broader spectrum activity and enhanced CNS efficacy. We recently developed a rat brain slice assay to assess the efficacy of AChE reactivators and mAChR antagonists against the acute effects of the organophosphorus AChE inhibitor 4-nitrophenyl isopropyl methylphosphonate (NIMP) in the basolateral amygdala (BLA). Here we introduce a complimentary anesthetized animal model to evaluate the same compoundsin vivowith concurrent monitoring of EEG and respiratory rate. We find that intravenous delivery of 0.5 mg/kg NIMP reliably produces seizure like activity in the BLA, with concurrent respiratory depression and eventual respiratory failure. The central effects of AChE reactivators and mAChR antagonists delivered intravenously are consistent with their expected ability to cross the BBB. Combining our previously describedin vitroassay with the methods described here provides a relatively comprehensive set of preclinical tools for evaluating the efficacy of novel MCMs. Notably, using these methods potentially obviates subjecting conscious animals to cholinergic crises, which aligns with the AAALAC’s 3Rs principle of refinement.
Quantitative and systematic NMR measurements of sequence-dependent A-T Hoogsteen dynamics uncovers unique conformational specificity in the DNA double helix
Authors: Manghrani Akanksha , Rangadurai Atul Kaushik , Szekely Or , Liu Bei , Guseva Serafima , Al-Hashimi Hashim M.
Published: May 2024

The propensities to form lowly-populated short-lived conformations of DNA could vary with sequence, providing an important source of sequence-specificity in biochemical reactions. However, comprehensively measuring how these dynamics vary with sequence is challenging. Using1H CEST and13CR1ρNMR, we measured Watson-Crick to Hoogsteen dynamics for an A-T base pair in thirteen trinucleotide sequence contexts. The Hoogsteen population and exchange rate varied 4-fold and 16-fold, respectively, and were dependent on both the 3’- and 5’-neighbors but only weakly dependent on monovalent ion concentration (25 versus 100 mM NaCl) and pH (6.8 versus 8.0). Flexible TA and CA dinucleotide steps exhibited the highest Hoogsteen populations, and their kinetics rates strongly depended on the 3’-neighbor. In contrast, the stiffer AA and GA steps had the lowest Hoogsteen population, and their kinetics were weakly dependent on the 3’-neighbor. The Hoogsteen lifetime was especially short when G-C neighbors flanked the A-T base pair. The Hoogsteen dynamics had a distinct sequence-dependence compared to duplex stability and minor groove width. Thus, our results uncover a unique source of sequence-specificity hidden within the DNA double helix in the form of A-T Hoogsteen dynamics and establish the utility of1H CEST to quantitively measure sequence-dependent DNA dynamics.
Developmental and adult striatal patterning of nociceptin ligand marks striosomal population with direct dopamine projections
Authors: Hueske Emily , Stine Carrie , Yoshida Tomoko , Crittenden Jill R. , Gupta Akshay , Johnson Joseph C. , Achanta Ananya S. , Loftus Johnny , Mahar Ara , Hul Dan , Azocar Jesus , Gray Ryan J. , Bruchas Michael R. , Graybiel Ann M.
Published: May 2024

Circuit influences on the midbrain dopamine system are crucial to adaptive behavior and cognition. Recent developments in the study of neuropeptide systems have enabled high-resolution investigations of the intersection of neuromodulatory signals with basal ganglia circuitry, identifying the nociceptin/orphanin FQ (N/OFQ) endogenous opioid peptide system as a prospective regulator of striatal dopamine signaling. Using a prepronociceptin-Cre reporter mouse line, we characterized highly selective striosomal patterning ofPnocmRNA expression in mouse dorsal striatum, reflecting early developmental expression ofPnoc. In the ventral striatum, Pnoc expression was was clustered across the nucleus accumbens core and medial shell, including in adult striatum. We found that PnoctdTomatoreporter cells largely comprise a population of dopamine receptor D1 (Drd1) expressing medium spiny projection neurons localized in dorsal striosomes, known to be unique among striatal projections neurons for their direct innervation of midbrain dopamine neurons. These findings provide new understanding of the intersection of the N/OFQ system among basal ganglia circuits with particular implications for developmental regulation or wiring of striatal-nigral circuits.
Synthesis and evaluation of chemical linchpins for highly selective CK2α targeting
Authors: Greco Francesco A. , Krämer Andreas , Wahl Laurenz , Elson Lewis , Ehret Theresa A. L. , Gerninghaus Joshua , Möckel Janina , Müller Susanne , Hanke Thomas , Knapp Stefan
Published: May 2024

Casein kinase-2 (CK2) are serine/threonine kinases with dual co-factor (ATP and GTP) specificity, that are involved in the regulation of a wide variety of cellular functions. Small molecules targeting CK2 have been described in the literature targeting different binding pockets of the kinase with a focus on type I inhibitors such as the recently published chemical probe SGC-CK2-1. In this study, we investigated whether known allosteric inhibitors binding to a pocket adjacent to helix αD could be combined with ATP mimetic moieties defining a novel class of ATP competitive compounds with a unique binding mode. Linking both binding sites requires a chemical linking moiety that would introduce a 90-degree angle between the ATP mimetic ring system and the αD targeting moiety, which was realized using a sulfonamide. The synthesized inhibitors were highly selective for CK2 with binding constants in the nM range and low micromolar activity. While these inhibitors need to be further improved, the present work provides a structure-based design strategy for highly selective CK2 inhibitors.
Viral chronotypes and their role in shaping seasonal viral dynamics in the Western English Channel
Authors: Bolaños Luis M. , Michelsen Michelle , Temperton Ben
Published: May 2024

Marine viruses are key players of ocean biogeochemistry, profoundly influencing microbial community ecology and evolution. Despite their importance, few studies have explored the temporal dynamics of viral genome abundances in marine environments. Viral dynamics are complex, influenced by multiple factors such as host population dynamics and environmental conditions. To disentangle the complexity of viral communities, we developed an unsupervised machine learning framework to classify viral genomes into “chronotypes” based on temporal abundance patterns. Analysing an inter-seasonal monthly time-series of surface viral metagenomes from the Western English Channel, we identified chronotypes and compared their functional and evolutionary profiles. Results revealed a consistent annual cycle with steep compositional changes from winter to summer and steadier transitions from summer to winter. Seasonal chronotypes were enriched in potential auxiliary metabolic genes like ferrochelatases and 2OG-Fe(II) oxygenases compared to non-seasonal types. Chronotypes clustered into four groups based on their correlation profiles with environmental parameters, primarily driven by temperature and nutrients. Viral genomes exhibited a rapid turnover of polymorphisms, akin to Red Queen dynamics. However, within seasonal chronotypes, some sequences exhibited annual polymorphism recurrence, which declined over a 16-month period, suggesting that a fraction of the seasonal viral populations evolve more slowly. Classification into chronotypes revealed viral genomic signatures linked to temporal patterns, likely reflecting metabolic adaptations to environmental fluctuations and host dynamics. This novel framework enables the identification of long-term trends in viral composition, environmental influences on genomic structure, and potential viral interactions.
Magnon-mediated topological superconductivity in a quantum wire
Authors: Viñas Boström Florinda , Viñas Boström Emil
Published: May 2024

Many emergent phases of matter stem from the intertwined dynamics of quasiparticles. Here we show that a topological superconducting phase emerges as the result of interactions between electrons and magnons in a quantum wire and a helical magnet. The magnon-mediated interaction favors triplet superconductivity over a large magnetic phase space region, and stabilizes topological superconductivity over an extended region of chemical potentials. The superconducting gap depends exponentially on the spin-electron coupling, allowing it to be enhanced through material engineering techniques.

Published by the American Physical Society
2024
How does institutional theory illuminate the influence of the digital economy on R&D networks?
Authors: Xing Zeyu , Fang Debin , Wang Jing , Zhang Lupeng
Published: May 2024

Purpose

The purpose of this research is to explore how an innovation organization's orientation toward the digital economy influences its position within R&D networks. By using institutional theory, the study aims to forecast market changes and understand how organizations can navigate the digital economy to secure essential resources and minimize dependencies.

Design/methodology/approach

This study employs a longitudinal panel dataset with 11,763 entries from 1995 to 2018, covering strategic emerging industries in China to analyze the impact of digital economy orientation on R&D networks. Utilizing advanced statistical models, it assesses the role of the legal environment as a moderator. This methodological approach facilitates a robust examination of the nexus between digital orientation and network dynamics within the context of institutional theory.

Findings

The study reveals that an organization's digital economy orientation enhances its centrality in R&D networks but reduces its control over structural holes. The legal environment negatively moderates the impact of digital economy orientation on network centrality, while positively influencing the relationship with network structural holes. These findings offer new insights into how institutional forces shape the strategic positioning of organizations in R&D collaborations.

Originality/value

This research offers a fresh perspective on the digital economy's impact on R&D networks, particularly in the Industry-University-Research (IUR) context. It extends the discourse by integrating institutional theory to elucidate the adaptation of R&D networks in the digital era. By identifying the legal environment as a moderator, the study provides a nuanced understanding of the strategic alignment within networks influenced by digital advancements. The unique focus on China's R&D networks presents a valuable contribution to the global discussion on digital integration and innovation ecosystems, highlighting the intersection of policy, academia, and industry in shaping research and development trajectories.