bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-task Intrinsic Cortical Activity in Novice and Experienced Military Specialists: A Cross-sectional Study
Authors: Silva R B , Ribeiro Pedro , Silva Siqueira Grace , Martins Cx Lilian
Published: July 2023

Introduction

Neuroscience studies brain dynamics through the analysis of electrical signals. Cortical activity estimated by electroencephalography brings accurate information about perceptions of human behavior. The examination of resting states in relation to subsequent behaviors indicates that intrinsic cortical activity (ICA) has implications for decision-making processes, especially when inserted in the context of military activities and associated with stress. The objective of this study was to compare the absolute alpha power (AAP) in the ICA in the pre-task moment of novice specialized military (NG) with experienced (ExpG), associating with the level of stress.

Materials and Methods

This was a cross-sectional, observational study with 19 military personnel (32.1 years old), divided into NG (10) and ExpG (9). The ICA was the outcome variable, with the level of stress and the time of specialization in military tasks as the exposure variables. ICA analysis were carried out based on the cortical areas to compare the ICA of the NG with that of the ExpG. The association of stress level with ICA was estimated by linear regression via linear models.

Results

There was a significant difference in almost all cortical areas, and the averages were always higher in Exp. The high stress level was associated with greater AAP both for the NG and for the ExpG, and at the medium level, the AAP was obtained, varying according to each cortical area.

Conclusion

The AAP in ExpG was significantly higher than that in NG, indicating a lower level of cortical activity and greater efficiency in sensory, motor, and visual tasks.
Patient and caregiver return to work after a primary brain tumor
Authors: Nicklin Emma , Phang Isaac , Short Susan C , Hoogendoorn Petra , Boele Florien W
Published: July 2023

Background

Studies focusing on the return to work (RTW) experiences of patients with a brain tumor (BT) are scarce. We aimed to explore, in-depth, the occupational expectations, experiences, and satisfaction of patients who RTW after a BT diagnosis and treatment, those not able to, and their family caregivers.

Methods

This multicenter, cross-sectional study utilized semi-structured interviews and reflexive thematic analysis. Interviews were conducted with adults diagnosed with primary BT, in employment/self-employed before diagnosis, currently in follow-up care, and also with their caregivers.

Results

In total, 23 interviews (17 patients/6 caregivers) took place. Five themes were developed: (1) Early (adjustments and) expectations: “Thought I would be back at work the following Monday”; pre-treatment patients wanted to be better informed about potential recovery time and side-effects. (2) Drivers to RTW: “Getting my life back on track”; RTW was seen as a symbol of normality and also dictated by financial pressures. (3) Experiences returning to work: “It’s had its ups and downs”: patients who had successfully returned were supported by employers financially, emotionally, and practically. (4) Required support: “He had surgery and that was it”: suggested support included a back-to-work scheme and comprehensive financial support. (5) Caring and paid work: The “juggling act”: carer’s work was significantly impacted; often reducing/increasing their working hours while managing increasing caring demands.

Conclusions

Future research focusing on RTW in neuro-oncology populations is needed. Interventions should be developed to improve employer/employee communication, and increase knowledge about BT care and possibilities for RTW, to support patients and caregivers towards sustained employment.
Searching for Majorana quasiparticles at vortex cores in iron-based superconductors
Authors: Machida Tadashi , Hanaguri Tetsuo
Published: July 2023

The unambiguous detection of the Majorana zero mode (MZM), which is essential for future topological quantum computing, has been a challenge in recent condensed matter experiments. The MZM is expected to emerge at the vortex core of topological superconductors as a zero-energy vortex bound state (ZVBS), amenable to detection using scanning tunneling microscopy/spectroscopy (STM/STS). However, the typical energy resolution of STM/STS has made it challenging to distinguish the MZM from the low-lying trivial vortex bound states. Here, we review the recent high-energy-resolution STM/STS experiments on the vortex cores of Fe(Se,Te), where the MZM is expected to emerge, and the energy of the lowest trivial bound states is reasonably high. Tunneling spectra taken at the vortex cores exhibit a ZVBS well below any possible trivial state, suggesting its MZM origin. However, it should be noted that ZVBS is a necessary but not sufficient condition for the MZM; a qualitative feature unique to the MZM needs to be explored. We discuss the current status and issues in the pursuit of such Majorananess, namely the level sequence of the vortex bound states and the conductance plateau of the ZVBS. We also argue for future experiments to confirm the Majorananess, such as the detection of the doubling of the shot-noise intensity and spin polarization of the MZM.
Comparison of Outcomes of Surgery Versus Implantable Device for the Treatment of Hearing Loss Associated With Congenital Aural Atresia: A Systematic Review and Meta-Analysis
Authors: Shannon Christian M. , Gutierrez Jorge A. , Nguyen Shaun A. , Meyer Ted A. , Lambert Paul R.
Published: July 2023

Objective

To compare audiometric outcomes, complications, and revisions required for implantable bone-conduction devices (BCDs) versus atresia surgery for the treatment of hearing loss associated with congenital aural atresia.

Databases Reviewed

PubMed, Scopus, CINAHL.

Methods

Databases were searched for English articles from inception to July 1, 2022, for studies reporting audiometric outcomes or complications for either BCDs or atresia surgery for the treatment of congenital aural atresia. Main outcome measures included pure-tone audiometry, air-bone gap, speech reception threshold, associated complications, and rates of revision for each treatment option.

Results

We identified 973 abstracts, of which 89 were selected for data extraction and analysis. A total of 2,611 patients were included, 1,901 in the atresia surgery group and 710 in the BCDs group. A meta-analysis of single means was conducted for age and audiometric outcomes, and a meta-analysis of proportions was conducted for complications and revisions. The average short-term improvement in pure-tone audiometry for the BCDs group was 34.4 ± 1.6 dB compared with 22.4 ± 1.5 dB for the atresia surgery group, representing a significant difference (12.0 dB; 95% confidence interval, 11.9–12.2; p < 0.0001). A smaller proportion of complications were reported in the devices group (16.9%) compared with the atresia surgery group (45.7%). In addition, a smaller proportion of cases in the devices group required some degree of revision (17.8%) compared with the atresia surgery group (23.0%).

Conclusions

This study demonstrates that implantable BCDs have significantly better audiometric outcomes as well as a lower rate of complications and revisions required compared with atresia surgery.
Automated Radiomic Analysis of Vestibular Schwannomas and Inner Ears Using Contrast-Enhanced T1-Weighted and T2-Weighted Magnetic Resonance Imaging Sequences and Artificial Intelligence
Authors: Neves Caio A. , Liu George S. , El Chemaly Trishia , Bernstein Isaac A. , Fu Fanrui , Blevins Nikolas H.
Published: July 2023

Objective

To objectively evaluate vestibular schwannomas (VSs) and their spatial relationships with the ipsilateral inner ear (IE) in magnetic resonance imaging (MRI) using deep learning.

Study Design

Cross-sectional study.

Patients

A total of 490 adults with VS, high-resolution MRI scans, and no previous neurotologic surgery.

Interventions

MRI studies of VS patients were split into training (390 patients) and test (100 patients) sets. A three-dimensional convolutional neural network model was trained to segment VS and IE structures using contrast-enhanced T1-weighted and T2-weighted sequences, respectively. Manual segmentations were used as ground truths. Model performance was evaluated on the test set and on an external set of 100 VS patients from a public data set (Vestibular-Schwannoma-SEG).

Main Outcome Measure(s)

Dice score, relative volume error, average symmetric surface distance, 95th-percentile Hausdorff distance, and centroid locations.

Results

Dice scores for VS and IE volume segmentations were 0.91 and 0.90, respectively. On the public data set, the model segmented VS tumors with a Dice score of 0.89 ± 0.06 (mean ± standard deviation), relative volume error of 9.8 ± 9.6%, average symmetric surface distance of 0.31 ± 0.22 mm, and 95th-percentile Hausdorff distance of 1.26 ± 0.76 mm. Predicted VS segmentations overlapped with ground truth segmentations in all test subjects. Mean errors of predicted VS volume, VS centroid location, and IE centroid location were 0.05 cm3, 0.52 mm, and 0.85 mm, respectively.

Conclusions

A deep learning system can segment VS and IE structures in high-resolution MRI scans with excellent accuracy. This technology offers promise to improve the clinical workflow for assessing VS radiomics and enhance the management of VS patients.
Quantitative Evaluations of Vestibular Function in Patients With Petrous Apex Cholesterol Granulomas Treated With an Endoscopic Transsphenoidal Approach: A Report of Two Cases
Authors: Fujiwara Yuuki , Fujiwara Keishi , Motegi Hiroaki , Ishi Yukitomo , Morita Shinya , Hoshino Kimiko , Fukuda Atsushi , Nakamaru Yuji , Homma Akihiro
Published: July 2023

Objective

We report two cases of petrous apex cholesterol granuloma (PACG) treated with an endoscopic transsphenoidal approach. Vestibular functions of the two patients were evaluated quantitatively by video Head Impulse Test (vHIT) and/or vestibular evoked myogenic potentials (VEMPs).

Patients

Two patients with PACG who experienced episodes of dizziness are presented.

Intervention

An endoscopic transsphenoidal approach to PACG.

Main Outcome Measure

The preoperative and postoperative vestibular functions as evaluated by vHIT and VEMP.

Results

Two cases of PACG were treated by a transsphenoidal approach. The internal auditory canal was compressed by the PACG in both cases. The patients both experienced episodes of dizziness before surgery and preoperative vestibular testing including vHIT and VEMP indicated dysfunction of vestibular nerves. After surgery, their symptoms were completely resolved, and the vestibular testing results were improved.

Conclusions

This article is noteworthy for being the first to publish quantitative vestibular function testing for patients with PACG with vestibular dysfunction. PACG may show various symptoms, with dizziness being one of the most common symptoms. In cases in which the internal auditory canal is compressed by the PACG, vestibular functions should be evaluated by vHIT and VEMP. In the present cases, dizziness was found to be resolved by surgery to release the compression on internal auditory canal. Based on the present cases, the transsphenoidal approach is considered to be both safe and effective.
Understanding the role of mask-wearing during COVID-19 on the island of Ireland
Authors: Fitz-Simon Nicola , Ferguson John , Alvarez-Iglesias Alberto , Sofonea Mircea T. , Kamiya Tsukushi
Published: July 2023

Non-pharmaceutical interventions have played a key role in managing the COVID-19 pandemic, but it is challenging to estimate their impacts on disease spread and outcomes. On the island of Ireland, population mobility restrictions were imposed during the first wave, but mask-wearing was not mandated until about six months into the pandemic. We use data on mask-wearing, mobility, and season, over the first year of the pandemic to predict independently the weekly infectious contact estimated by an epidemiological model. Using our models, we make counterfactual predictions of infectious contact, and ensuing hospitalizations, under a hypothetical intervention where 90% of the population wore masks from the beginning of community spread until the dates of the mask mandates. Over periods including the first wave of the pandemic, there were 1601 hospitalizations with COVID-19 in Northern Ireland and 1521 in the Republic of Ireland. Under the counterfactual mask-wearing scenario, we estimate 512 (95% CI 400, 730) and 344 (95% CI 266, 526) hospitalizations in the respective jurisdictions during the same periods. This could be partly due to other factors that were also changing over time.
Fission–fusion dynamics in sheep: the influence of resource distribution and temporal activity patterns
Authors: Della Libera Katja , Strandburg-Peshkin Ariana , Griffith Simon C. , Leu Stephan T.
Published: July 2023

Fission–fusion events, i.e. changes to the size and composition of animal social groups, are a mechanism to adjust the social environment in response to short-term changes in the cost–benefit ratio of group living. Furthermore, the time and location of fission–fusion events provide insight into the underlying drivers of these dynamics. Here, we describe a method for identifying group membership over time and for extracting fission–fusion events from animal tracking data. We applied this method to high-resolution GPS data of free-ranging sheep (Ovis aries). Group size was highest during times when sheep typically rest (midday and at night), and when anti-predator benefits of grouping are high while costs of competition are low. Consistent with this, fission and fusion frequencies were highest during early morning and late evening, suggesting that social restructuring occurs during periods of high activity. However, fission and fusion events were not more frequent near food patches and water resources when adjusted for overall space use. This suggests a limited role of resource competition. Our results elucidate the dynamics of grouping in response to social and ecological drivers, and we provide a tool for investigating these dynamics in other species.
Kinship composition in mammals
Authors: Pereira André S. , De Moor Delphine , Casanova Catarina , Brent Lauren J. N.
Published: July 2023

Understanding the evolution of group-living and cooperation requires information on who animals live and cooperate with. Animals can live with kin, non-kin or both, and kinship structure can influence the benefits and costs of group-living and the evolution of within-group cooperation. One aspect of kinship structure is kinship composition, i.e. a group-level attribute of the presence of kin and/or non-kin dyads in groups. Despite its putative importance, the kinship composition of mammalian groups has yet to be characterized. Here, we use the published literature to build an initial kinship composition dataset in mammals, laying the groundwork for future work in the field. In roughly half of the 18 species in our sample, individuals lived solely with same-sex kin, and, in the other half, individuals lived with related and unrelated individuals of the same sex. These initial results suggest that it is not rare for social mammals to live with unrelated individuals of the same sex, highlighting the importance of considering indirect and direct fitness benefits as co-drivers of the evolution of sociality. We hope that our initial dataset and insights will spur the study of kinship structure and sociality towards new exciting avenues.
Ecology of fear: predator avoidance reduces seed dispersal in an ant
Authors: Gálvez Dumas
Published: July 2023

The ecology of fear refers to the non-fatal cost that predators and parasites impose on prey populations. These non-consumptive effects (NCEs) can influence animal–plant interactions, but evidence thereof comes mainly from vertebrate systems with less focus on invertebrates. Here, I investigated whether the foraging behaviour of the ant
Ectatomma ruidum
was influenced by its primary predator, the forest toad
Rhinella alata
. In field tests, the probability of seed removal by the ants was 25% for seeds placed with the forest toad compared to 32% for control seeds, suggesting that toads reduce ant foraging rates. A further experiment revealed that ants which had previously encountered the predator and its faeces were more likely (59%) than inexperienced ants (50%) to avoid the exit with the predator faeces. This outcome suggests that ants are capable of learning cues associated with predation risk, possibly leading to NCEs. This indicates that predators can exert NCEs on invertebrate prey with potential cascading effects on seed dispersal, extending results previously seen only in vertebrate seed dispersal systems.
Pharmacological Evaluations of Select Herbal Extracts on TLR7/8-induced Cytokine and Chemokine Production in Macrophage-like Cells
Authors: Dagar Manisha , Priya Kamala , Dikshit Madhu , Kumar Ajay
Published: July 2023

Inflammation is an innate immune response triggered by harmful stimuli, such as pathogens, tissue injury, or toxins. The purpose is to eliminate the source of infection and initiate the healing process. However, an excessive acute inflammatory response can lead to severe and life-threatening complications, as seen during recent pandemics. In the context of viral infections, the activation of the TLR7/8 signaling pathway has been implicated in excessive cytokine secretion. In this study, we aimed to replicate the perturbed inflammatory environment resulting from the activation of the TLR7/8 specific agonists, imiquimod, and resiquimod.

We utilized macrophage-like cells, as macrophages are the first responders during infections and secrete key pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) to recruit immune cells to the site of infection. Herbal medicines have been traditionally used for centuries to enhance respiratory immune function. In the present study, we employed a prophylactic approach, where macrophage-like THP1 cells, differentiated with PMA, were pre-treated with select herbal extracts/formulations prior to TLR7/8 activation in the presence of agonists.

Several medicinal plants and formulations known for their therapeutic potential in respiratory ailments were investigated, includingWithania somnifera, Tinospora cordifolia, Glycyrrhiza glabra,and AYUSH-64, an herbal formulation. The gene expression and corresponding secreted levels of various inflammatory mediators were measured using RT-PCR and ELISA methods, respectively, in treated and untreated differentiated THP1 cells induced with TLR7/8 agonists. Comparatively, the gene expression of inflammatory markers was significantly higher in resiquimod-induced cells than in imiquimod-treated cells. Notably,Withania somniferademonstrated pronounced prophylactic efficacy compared to other herbs/formulations, as evidenced by reduction in expression of majority of investigated inflammatory marker genes.
A Vibrating Ingestible BioElectronic Stimulator Modulates Gastric Stretch Receptors for Illusory Satiety
Authors: Srinivasan Shriya S. , Alshareef Amro , Hwang Alexandria , Bryne Ceara , Kuosmann Johannes , Ishida Keiko , Jenkins Joshua , Liu Sabrina , Madani Wiam Abdalla Mohammed , Hayward Alison M , Fabian Niora , Traverso Giovanni
Published: July 2023

Effective therapies for obesity either require invasive surgical or endoscopic interventions or high patient adherence, making it challenging for the nearly 42% of American adults who suffer from obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. Here we developed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill - an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release as well as yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (∼40%, p< 0.0001) and minimized the weight gain rate (p< 0.03) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.
Lawful kinematics link eye movements to the limits of high-speed perception
Authors: Rolfs Martin , Schweitzer Richard , Castet Eric , Watson Tamara L. , Ohl Sven
Published: July 2023

Perception relies on active sampling of the environment. What part of the physical world can be sensed is limited by biophysical constraints of sensory systems, but might be further constrained by the kinematic bounds of the motor actions that acquire sensory information. We tested this fundamental idea for humans’ fastest and most frequent behavior—saccadic eye movements—which entails retinal motion that commonly escapes visual awareness. We discover that the visibility of a high-speed stimulus, presented during fixation, is predicted by the lawful sensorimotor contingencies that saccades routinely impose on the retina, reflecting even distinctive variability between observers’ movements. Our results suggest that the visual systems’ functional and implementational properties are best understood in the context of movement kinematics that impact its sensory surface.
Revisiting a classical theory of sensory specificity: assessing consistency and stability of thermosensitive spots
Authors: Ezquerra-Romano Ivan , Clements Michael F. , di Costa Steven , Iannetti Gian Domenico , Haggard Patrick
Published: July 2023

Thermal sensitivity is not uniform across the skin, and is particularly high in small (∼1mm2) regions termed ‘thermosensitive spots’. These spots are thought to reflect the anatomical location of specialised thermosensitive nerve endings from single primary afferents. Thermosensitive spots provide foundational support for “labelled line” or specificity theory of sensory perception, which state that different sensory qualities are transmitted by separate and specific neural pathways. This theory predicts a highly stable relation between repetitions of a thermal stimulus and the resulting sensory quality, yet these predictions have rarely been tested systematically. Here we present the qualitative, spatial and repeatability properties of 334 thermosensitive spots on the dorsal forearm sampled across 4 separate sessions. In line with previous literature, we found that spots associated with cold sensations (112 cold spots, 34%) were more frequent than spots associated with warm sensations (41 warm spots, 12%). Still more frequent (165 spots, 49%) were spots that elicited inconsistent sensations when repeatedly stimulated by the same temperature. Remarkably, only 13 spots (4%) conserved their position between sessions. Overall, we show unexpected inconsistency of both the perceptual responses elicited by spot stimulation and of spot locations across time. These observations call to revise the traditional view that thermosensitive spots reflect the location of individual thermosensitive, unimodal primary afferents serving as specific labelled lines for corresponding sensory qualities.

New & Noteworthy

Thermosensitive spots are clustered rather than randomly distributed, and have highest density near the wrist. Surprisingly, we found that thermosensitive spots elicit inconsistent sensory qualities and are unstable over time. Our results question the widely believed notion that thermosensitive spots reflect the location of individual thermoreceptive, unimodal primary afferents, that serve as labelled lines for corresponding sensory qualities.
On the structure of an evolutionary transition: dependence and cohesion in incipient endosymbioses
Authors: Athreya Gaurav S. , Czuppon Peter , Gokhale Chaitanya S.
Published: July 2023

How did biological organisms become so complex? Endosymbiosis is the prototypical example of an egalitarian evolutionary transition and is central to the origins of many complex biological systems. Why do only some symbioses undergo evolutionary transitions, and how does the host-symbiont relationship change during this process? Here, we characterise endosymbiosis by two emergent collective-level properties: the relationship between the host and symbiont (mutual dependence) and reproduction (reproductive cohesion). Using methods from adaptive dynamics, we study the co-evolution of the traits underlying these properties. Our central result is a robust demonstration that even when investments in dependence and cohesion are uncorrelated, host-symbiont mutual dependence arises faster than reproductive cohesion. Further, we show that the collective’s formation and shared fate, coupled with different generation times of the host and symbiont, leads to an emergent asymmetry in how much they invest in the collective. Lastly, we account for biological realism that previous models have ignored and show that this can preclude a successful evolutionary transition towards stable endosymbiosis. Together, this work uncovers a fundamental property of endosymbioses, highlighting the immense effects of simple ecological factors and providing a clear way forward for theoretical and empirical investigations.
Two distinct mechanisms of flavoprotein spectral tuning revealed by low-temperature and time-dependent spectroscopy
Authors: Nikolaev Andrey , Tropina Elena V. , Boldyrev Kirill N. , Maksimov Eugene G. , Borshchevskiy Valentin , Mishin Alexey , Yudenko Anna , Kuzmin Alexander , Kuznetsova Elizaveta , Semenov Oleg , Remeeva Alina , Gushchin Ivan
Published: July 2023

Flavins such as flavin mononucleotide or flavin adenine dinucleotide are bound by diverse proteins, yet have very similar spectra when in the oxidized state. Recently, we developed new variants of flavin-binding protein CagFbFP exhibiting notable blue (Q148V) or red (I52V A85Q) shifts of fluorescence emission maxima. Here, we use time-resolved and low temperature spectroscopy to show that whereas the chromophore environment is static in Q148V, an additional protein-flavin hydrogen bond is formed upon photoexcitation in the I52V A85Q variant. Consequently, in Q148V, excitation, emission and phosphorescence spectra are shifted, whereas in I52V A85Q, excitation and low-temperature phosphorescence spectra are relatively unchanged, while emission spectrum is altered. We also determine X-ray structures of the two variants to reveal the flavin environment and complement the spectroscopy data. Our findings illustrate two distinct color tuning mechanisms of flavin-binding proteins and pave the way for engineering of new variants with improved optical properties.

TOC GRAPHICS
Theta cycle dynamics of spatial representations in the lateral septum
Authors: Bzymek Katarzyna , Kloosterman Fabian
Published: July 2023

An internal representation of the environment – or map – allows animals to evaluate multiple routes and adapt their navigation strategy to current needs and future goals. The hippocampal formation plays a crucial role in learning a spatial map and using the map for goal-directed navigation. The lateral septum forms a major node for connections between the hippocampus and subcortical brain regions that could link the spatial map to motivation and reward processing centers such as the ventral tegmental area and hypothalamus. It is not known, however, how the lateral septum contributes to the processing of spatial information and route planning.

In this study, we investigated the temporal dynamics of spatial representations in the lateral septum. Neuropixels probes were used to record cellular activity along the dorsal-ventral extent of the lateral septum while rats performed one of two spatial navigation tasks in a Y-maze. The activity of a large fraction of cells was theta rhythmic and a subset of cells showed evidence of being active on alternate theta cycles (theta cycle skipping). Both theta rhythmicity and cycle skipping were strongest in the dorsal lateral septum. Similarly, spatially selective firing was most prominent in the dorsal lateral septum. Using neural decoding, we show that the lateral septum cell population encodes both the current location and alternatingly the possible future paths within single theta cycles when rats approach the choice point in the maze.

Our data further shows that the alternating expression of spatial representations in the lateral septum is task-dependent, such that it is strongest when the task also requires the animals to alternate between rewarded goal arms. These data suggest that task demands and experience shape which representations are activated near a choice point. The lateral septum receives strong input from hippocampal place cells, and while there may be integration and transformation of incoming spatial signals, our findings support the idea that hippocampal spatial representations and their temporal dynamics are conveyed to subcortical projection areas through the lateral septum.
Biologically meaningful regulatory logic enhances the convergence rate in Boolean networks and bushiness of their state transition graph
Authors: Sil Priyotosh , Subbaroyan Ajay , Kulkarni Saumitra , Martin Olivier C. , Samal Areejit
Published: July 2023

Boolean network (BN) models of gene regulatory networks (GRNs) have gained widespread traction as they can easily recapitulate cellular phenotypes via their attractor states. The overall dynamics of such models are embodied in the system’sstate transition graph(STG) which is highly informative. Indeed, even if two BN models have the same network structure and recover the same attractors, their STGs can be drastically different depending on the type of regulatory logic rules or Boolean functions (BFs) employed. A key objective of the present work is to systematically delineate the effects of different classes of regulatory logic rules on the structural features of the STG of reconstructed Boolean GRNs, while keeping BN structure and biological attractors fixed. Furthermore, we ask how such global features might be driven by characteristics of the underlying BFs. For that, we draw from ideas and concepts proposed in cellular automata for both the structural features and their associated proxies. We use the network of 10 reconstructed Boolean GRNs to generate ensembles that differ in the type of logic used while keeping their structure fixed and recovering their biological attractors, and compute quantities associated with the structural features of the STG: ‘bushiness’ and ‘convergence’, that are based on the number of garden-of-Eden (GoE) states and transient times to reach attractor states when originating at them. We find that ensembles employingbiologically meaningfulBFs have higher ‘bushiness’ and ‘convergence’ than those employing random ones. Computing these ‘global’ measures gets expensive with larger network sizes, stressing the need for more feasible proxies. We thus adapt Wuensche’sZ-parameter to BFs in BNs and provide 4 natural variants, which along with the network sensitivity, comprise our descriptors oflocaldynamics. One variant of the networkZ-parameter as well as the network sensitivity correlate particularly very well with the bushiness, serving as a good proxy for the same. Finally, we provide an excellent proxy for the ‘convergence’ based on computing transient lengths originating at random states rather thanGoEstates.
The ACE-inhibitor drug captopril inhibits ACN-1 to control dauer formation and aging
Authors: Egan Brian M. , Pohl Franziska , Anderson Xavier , Williams Shoshana C. , Adodo Imienreluefe Gregory , Hunt Patrick , Wang Zuoxu , Chiu Chen-Hao , Scharf Andrea , Mosley Matthew , Kumar Sandeep , Schneider Daniel L. , Fujiwara Hideji , Hsu Fong-Fu , Kornfeld Kerry
Published: July 2023

The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan inC. elegans,Drosophila, and rodents, but its mechanism is not well defined. Here we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice. To investigate the mechanism, we performed a forward genetic screen for captopril hypersensitive mutants. We identified a missense mutation that causes a partial loss-of-function of thedaf-2receptor tyrosine kinase gene, a powerful regulator of aging. The homologous mutation in the human insulin receptor causes Donohue syndrome, establishing these mutant worms as an invertebrate model of this disease. Captopril functions inC. elegansby inhibiting ACN-1, the worm homolog of ACE. Reducing the activity ofacn-1via captopril or RNAi promoted dauer larvae formation, suggestingacn-1is adafgene. Captopril-mediated lifespan extension xwas abrogated bydaf-16(lf)anddaf-12(lf)mutations. Our results indicate that captopril andacn-1control aging by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control.

Summary Statement

Captopril andacn-1control aging. By demonstrating they regulate dauer formation and interact withdafgenes, including a new DAF-2(A261V) mutant corresponding to a human disease variant, we clarified the mechanism.
Updated Biomarkers for TNBC in African vs. Caucasian American Women
Authors: Croft Jacob , Quintanar Odalys , Zhang Jun
Published: July 2023

Introduction

Breast cancer, especially triple-negative breast cancer (TNBC), is a significant concern in the US, being the most common cancer among women and the second leading cause of cancer-related deaths. TNBC lacks crucial receptors targeted in other breast cancer types, leading to a poor prognosis and limited treatment options due to its aggressive and heterogeneous nature.

Significance

African American women (AAW) with TNBC face higher mortality rates and more aggressive disease compared to Caucasian American women (CAW). Despite efforts to find biomarkers specific to AAW and CAW with TNBC, limited sample availability and data resources have been obstacles.

Methods

In our study, we examined 237 candidate peptide biomarkers using publicly available data.

Results

identify 23 unique prognostic biomarkers. These biomarkers accurately assess patient conditions based on race-specific gene expression patterns, holding potential to address racial disparities in TNBC treatment.

Conclusion

Overall, our research sheds light on how racial genetic profiles influence TNBC prognosis and treatment efficacy. The identified prognostic biomarkers pave the way for future studies addressing TNBC racial disparities and personalized treatment approaches.
Positive and negative feedback regulation of the TGF-β1–SMAD4 axis explains two equilibrium states in human skin aging
Authors: Haga Masatoshi , Iida Keita , Okada Mariko
Published: July 2023

Skin homeostasis during aging is critical not only for the appearance but also biological defense of the human body. In this study, we identified thrombospondin-1 (THBS1) and fibromodulin (FMOD) as positive and negative regulators, respectively, of the TGF-β1–SMAD4 axis in human skin aging based onin vitroandin vivoomics analyses and mathematical modeling. Transcriptomic and epigenetic analyses of senescent dermal fibroblasts identified TGF-β1 as the key upstream regulator. Bifurcation analysis identified a binary senescent/non-senescent switch, with THBS1 as the main controller. Sensitivity analysis of the TGF-β1 signaling pathway indicated that THBS1 expression was sensitively regulated while FMOD was robustly regulated, suggesting that THBS1 is a controllable factor. Inhibition of SMAD4 complex formation was experimentally validated as a promising manner to control THBS1 production and senescence. This study demonstrates the potential of a data-driven mathematical approach in determining the mechanisms of skin aging.

Graphical abstract

eTOC Blurb

Haga, Iida and Okada revealed that the balance between FMOD and THBS1 determines the two equilibrium states of skin homeostasis and THBS1 is a controllable factor in skin aging

Highlights

Multi-omics analysis identified TGF-β1–SMAD4 as key regulators in human skin aging

THBS1 and FMOD promoted and suppressed factors in skin aging, respectively

THBS1 controlled the senescent and non-senescent states of the aging switch

SMAD4 is a potential target for inhibiting THBS1 expression and cell senescence
Alternative splicing and its regulation in the malaria vectorAnopheles gambiae
Authors: Díaz-Terenti Bárbara , Gómez-Díaz Elena
Published: July 2023

Alternative splicing (AS) is a highly conserved mechanism that allows to expand the coding capacity of the genome, by modifying how multiple isoforms are expressed or used to generate different phenotypes. Despite its importance in physiology and disease, genome-wide studies of AS are lacking in most insects, including mosquitoes. Even for model organisms, chromatin associated processes involved in the regulation AS are poorly known. In this study, we investigated AS in the mosquitoAnopheles gambiaein the context of tissue-specific gene expression and mosquito responses to aPlasmodium falciparuminfection, as well as the relationship between patterns of differential isoform expression and usage with chromatin accessibility changes. For this, we combined RNA-seq and ATAC-seq data fromA. gambiaemidguts and salivary glands, and from infected and non-infected midguts. We report differences between tissues in the expression of 456 isoforms and in the use of 211 isoforms. Secondly, we find a clear and significant association between chromatin accessibility states and tissue-specific patterns of AS. The analysis of differential accessible regions located at splicing sites permitted the identification of several motifs resembling the binding sites ofDrosophilatranscription factors. Finally, the genome-wide analysis of tissue-dependent enhancer activity revealed that approximately 20% ofA. gambiaetranscriptional enhancers annotate to a differentially expressed or used isoform and that their activation status is linked to AS differences between tissues. This research illuminates the role of AS in gene expression in vector mosquitoes, and identifies regulatory regions potentially involved in AS regulation, which could reveal novel strategies for vector control.
Reference genome for the Northern bat (Eptesicus nilssonii), a most northern bat species
Authors: Laine Veronika N. , Pulliainen Arto T. , Lilley Thomas M.
Published: July 2023

The northern bat (Eptesicus nilssonii) is the most northern bat species in the world. Its distribution covers whole Eurasia, and the species is thus well adapted to different habitat types. However, recent population declines have been reported and rapid conservation efforts are needed. Here we present a high-qualityde novogenome assembly of a female northern bat from Finland (BLF_Eptnil_asm_v1.0). The assembly was generated using a combination of Pacbio and Omni-C technologies. The primary assembly comprises 726 scaffolds spanning 2.0 Gb, represented by a scaffold N50 of 102 Mb, a contig N50 of 66.2 Mb, and a BUSCO completeness score of 93.73%. Annotation of the assembly identified 20,250 genes. This genome will be an important resource for the conservation and evolutionary genomic studies especially in understanding how rapid environmental changes affect northern species.
Multi-level processing of emotions in life motion signals revealed through pupil responses
Authors: Yuan Tian , Wang Li , Jiang Yi
Published: July 2023

Perceiving emotions from the movements of other biological entities is critical for human survival and interpersonal interactions. Here, we report that emotional information conveyed by point-light biological motion (BM) triggered automatic physiological responses as reflected in pupil size. Specifically, happy BM evoked larger pupil size than neutral and sad BM, while sad BM induced a smaller pupil response than neutral BM. Moreover, this happy over sad pupil dilation effect is negatively correlated with individual autistic traits. Notably, emotional BM with only local motion features retained could also exert modulations on pupils. Compared with intact BM, both happy and sad local BM evoked stronger pupil responses than neutral local BM starting from an earlier timepoint, with no difference between the happy and sad conditions. These results revealed a fine-grained pupil-related emotional modulation induced by intact BM and a coarse but rapid modulation by local BM, demonstrating multi-level processing of emotions in life motion signals. Taken together, our findings shed new light on BM emotion processing, and highlight the potential of utilizing the emotion-modulated pupil response to facilitate the diagnosis of social cognitive disorders.
Beyond Traditional Methods: Innovative Integration of LISS IV and Sentinel 2A Imagery for Unparalleled Insight into Himalayan Ibex Habitat Suitability
Authors: Dutta Ritam , Joshi Bheem Dutt , Kumar Vineet , Sharief Amira , Bhattcharjee Saurav , Babu Rajappa , Thakur Mukesh , Sharma Lalit Kumar
Published: July 2023

Despite advancements in remote sensing, satellite imagery is underutilized in conservation research. Multispectral data from various sensors have great potential for mapping landscapes, but distinct spectral and spatial resolution capabilities are crucial for accurately classifying wildlife habitats. Our study aimed to develop a technique for precisely discerning habitat categories for the Himalayan Ibex (Capra sibirica) using different satellite imagery. To address both spectral and spatial challenges, we utilized LISS IV and Sentinel 2A data and integrated the LISS IV data with Sentinel 2A data along with their corresponding geometric information. Employing multiple supervised classification algorithms, we found the Random Forest (RF) algorithm to outperform others. The integrated (LISS IV-Sentinel 2A) classified image achieved the highest accuracy, with an overall accuracy of 86.17% and a Kappa coefficient of 0.84.

To map the suitable habitat of the Ibex, we conducted ensemble modeling using the Land Cover Land Use (LCLU) of all three image types (LISS IV, Sentinel 2A, Integrated) and other predictors such as topographical, soil type, vegetation, and water radiometric indices. The integrated model provided the most accurate prediction of suitable habitat for the Ibex, surpassing the other two LCLU classes derived from individual images. The Soil Adjusted Vegetation Index (SAVI) and elevation were identified as crucial factors in identifying suitable habitats

These findings hold valuable implications for the development of effective conservation strategies, as accurate classification schemes enable the identification of vital landscape elements. By precisely classifying LULC satellite images and identifying crucial habitats for the Ibex, this pilot study provides a new and valuable strategy for conservation planning. It enhances our ability to preserve and protect the habitat of wildlife species in the mountain ecosystem of the Himalayas.
Transcriptional regulation of Dyskerinviacanonical WNT signaling modulates sphingolipid biosynthesis and drives colorectal cancer
Authors: Nigam Shivansh , Khan Umar K. , Praveen Ayush , Shendre Akshay , Carskadon Shannon , Kapoor Abhimanyu , Tiwari Anjali , Chandra Abhijit , Palanisamy Nallasivam , Ateeq Bushra
Published: July 2023

Targeting EGFR has been effective in RAS/RAF wild-type colorectal cancer (CRC) patients. However, residual tumor relapses, necessitating the importance of biomarker-guided novel therapeutics. We show elevated DKC1 in ∼88% of CRC patients with poor recurrence-free survival. Clinically,DKC1-positive patients exhibit similarity with CMS2 class, the canonical subtype with active WNT signaling. We show functional significance of DKC1 in cell proliferation, stemness, DNA repair, and survival. Further, mice bearingDKC1knockdown xenografts show ∼81% reduction in tumor burden. Mechanistically, WNT/β-catenin signaling orchestratesDKC1expression, then, DKC1/SOX2 complex regulatesSGPP2, modulating sphingolipids metabolism. Downregulation of DKC1 in CRC lead to reduced SGPP2 levels leading to dysregulation of sphingolipid biosynthesis. Of note,DKC1-high CRC patients show accumulation of ceramides, namely C23 and C24, signifying their utility in diagnosis. Collectively, we delineate the mechanistic circuitry involved in DKC1-mediated CRC progression, propose ceramides as biomarker, and underscore WNT-based therapeutics for DKC1-positive patients.
A Polygenic Quincunx
Authors: Stern Ralph H.
Published: July 2023

Sequential addition of SNPs (single nucleotide polymorphism) to a risk model repeatedly splits risk groups in two, generating a branching tree. As SNPs are independent, the path of an individual through the tree is a form of random walk. This resembles the path of a ball through a Galton quincunx, but the rules for a polygenic quincunx are more complex. The result is that individuals zigzag to higher and lower risks with each additional SNP. Patient flows through a polygenic quincunx for a few SNPs that aggregate these individual random walks is presented. Longer random walks calculated from Monte-Carlo simulations illustrate how different the individual random walks can be. As random walks do not have unique termini, polygenic risk values don’t converge on unique individual risk estimates. However, the more steps in a random walk, the greater the dispersion of the termini around the starting point. So more SNPs can result in more disperse population polygenic risk distributions, and potentially greater clinical benefit when allocating preventive measures based on risk level.
Profiling the Expression of Transportome Genes in cancer: A systematic approach
Authors: Visentin Luca , Scarpellino Giorgia , Munaron Luca , Ruffinatti Federico Alessandro
Published: July 2023

The transportome, the-omiclayer encompassing all Ion Channels and Transporters (ICTs), is crucial for cell physiology. It is therefore reasonable to hypothesize a role of the transportome in disease, and in particular in cancer. Here, we present the Membrane Transport Protein DataBase (MTP-DB), a database collecting information on ICTs, and a pipeline that takes expression data and the MTP-DB as input to produce a broad overview of transportome dysregulation in cancer. The MTP-DB may prove useful for the study of the transportome in general, and the pipeline may be used to study the transportome in other diseases. Both tools are open source and can be found on GitHub at TCP-Lab/mtp-db and TCP-Lab/transportome_profiler, under permissive licenses. We detect that the transportome is dysregulated in cancer, and that dysregulation patterns are shared among different cancer types. It is still unclear how these patterns are linked to cancer patho-physiology.