bluuebunny/crossref_metadata_2025 huggingface dataset:
Facial Symmetry Enhancement and Brain Network Modifications in Facial Palsy Patients after Botulinum Toxin Type A Treatment
Authors: Ma Hao , Zhou Yu-lu , Wang Wen-jin , Chen Gang , Zhang Chen-hao , Lu Ye-chen , Wang Wei
Published: August 2024

Background:

Facial palsy, often resulting from trauma or iatrogenic treatments, leads to significant aesthetic and functional impairment. Surgical interventions, such as masseteric-to-facial nerve transfer combined with static suspension, are frequently recommended to restore facial nerve function and symmetry.

Methods:

This study examined the impact of botulinum toxin type A (BoNT-A) treatment on the unaffected side with regard to facial symmetry and brain connectivity in patients with severe oral commissure droop from facial nerve damage. Patients were divided into 2 groups: 1 group received BoNT-A injections on the unaffected side, and the other did not.

Results:

The authors’ findings revealed that BoNT-A treatment not only improved facial symmetry but also induced significant modifications in brain functional network connectivity. These modifications extended beyond the sensorimotor network, involving high-level cognitive processes, and exhibited a significant correlation with the degree of facial asymmetry.

Conclusions:

These results provide valuable insights into the mechanisms underlying the positive effects of BoNT-A intervention on motor recovery and brain plasticity in facial palsy patients. Furthermore, the study emphasizes the importance of a multidisciplinary approach to facial palsy rehabilitation. Understanding these intricate interactions between facial symmetry restoration and brain network adaptations may pave the way for more effective treatments and improved quality of life for individuals dealing with facial palsy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Nasal Tip Deprojection in Rhinoplasty
Authors: Datta Shaishav , Tugertimur Buğra , Hanna Steven A. , Goote Paige , Morris Matthew , Mattos David , Reish Richard G.
Published: August 2024

Background:

Rhinoplasty is one of the most commonly performed facial operations in the United States, and many major and minor nasal tip support structures affect tip projection. Overprojection may result from anatomical factors or occur iatrogenically during primary rhinoplasty. Achieving reliable, reproducible, and stable results is the aim of nasal tip deprojection rhinoplasty. The authors’ technique is designed to decrease nasal tip deprojection in patients with an overly projected nasal tip.

Methods:

A retrospective chart review of 2003 rhinoplasty cases in the senior author’s (R.G.R.) practice was conducted for the period between July of 2014 and June of 2022. The inclusion criteria were cosmetic or functional rhinoplasty cases with nasal tip deprojection, with a minimum of 12 months of follow-up. Outcomes of interest included the rate of operative revisions and the rate of postoperative infection.

Results:

A total of 447 patients met the inclusion criteria. The mean age of our study group was 32.1 years, with 409 female patients, and 291 cases were primary rhinoplasties. The mean follow-up period was 22.4 months. Eight patients (1.8%) required empiric antibiotics postoperatively, and 17 patients (3.8%) required operative revision.

Conclusions:

The authors’ case series demonstrates that combining resection of the medial crura with lateral crural steal and a columellar strut graft allows the surgeon to achieve considerable nasal tip deprojection. The comprehensive patient follow-up (mean, 22.4 months) further supports the reliability of the authors’ technique.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Effect of Tourniquet-Related Nerve Ischemia on Response to Handheld Nerve Stimulation in Ulnar Nerve Transposition
Authors: Brogan David M. , Lee Tony Y. , Beamer Yosita , Dy Christopher J.
Published: August 2024

Background:

Tourniquet-related nerve ischemia has been well studied in several reconstructive procedures, but the time course of impaired response to intraoperative stimulation is unclear. The present study evaluated ischemic effects on conduction during ulnar nerve transposition and examined the relationship between intraoperative and preoperative diagnostics. The authors hypothesized that intraoperative ischemia would have minimal impact on conduction.

Methods:

Thirty patients scheduled for anterior transposition were enrolled after preoperative examination, electrodiagnostic testing, and ultrasound. Demographic and symptom severity data were recorded. A handheld biphasic nerve stimulator was used intraoperatively to assess minimum amplitude and pulse duration needed for muscle response. Measurements were taken at 15-minute intervals after placement.

Results:

Changes in threshold amplitude and pulse duration were calculated between each 15-minute interval; no significant difference was found in the change of either value (P = 0.70 and P = 0.178). A weak negative correlation existed between preoperative compound muscle action potential amplitudes and average intraoperative pulse duration, which increased to a moderate correlation when compared with 45-minute pulse duration (r = −0.62; P < 0.01). Preoperative ulnar nerve cross-sectional area demonstrated no significant correlation with average pulse duration but a moderate correlation with pulse duration at 45 minutes (r = 0.63; P = 0.01).

Conclusions:

Tourniquet use did not prevent effective intraoperative stimulation of the ulnar nerve for at least 45 minutes. The window for meaningful stimulation with tourniquet use appears to be greater than previously thought. Preoperative nerve compound muscle action potential amplitude and cross-sectional area does appear to influence pulse duration required after 45 minutes of ischemia, suggesting that injured nerves are more susceptible to ischemia.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Primary Maxillary Hypoplasia in Complete Unilateral Cleft Lip and Palate: Analysis of Clinical Data and Associations
Authors: Scarpa Marcela B. , Câmara Paulo R.P. , Fabiani Isadora M. , Melhem-Elias Fernando , Tames Hugo L.V.C. , Dornelles Rodrigo , Alonso Nivaldo
Published: August 2024

Objective:

Investigate the volumetric differences between the cleft and noncleft hemi-maxillae in patients with complete unilateral CLP and compare them with the average population. It also aimed to correlate the hemi-maxilla volumetry with maxillary sinuses’ volumes, with the occlusal index in digitized models and tooth agenesis.

Design:

This is a retrospective cohort study. Setting: Cleft lip and palate center in quaternary-level institutions.

Patients, Participants:

This study included 23 patients with complete unilateral CLP who underwent cheiloplasty between 2008 and 2012 and a control group of 24 patients without craniofacial abnormalities.

Interventions:

None.

Main Outcome Measure(S):

The computed tomography scans of cleft patients were analyzed before and after alveolar bone grafting. Following 3-dimensional tomographic reconstruction, a volumetric index was calculated as the ratio of cleft and normal side volumes (CV/NV). Cuts and measurements were also conducted in the control group. Additionally, the volumetric index of the maxillary sinuses (MSCV/MSNV) was calculated, and occlusal index analyses were performed using digitized models. In addition, dental agenesis was observed.

Results:

The CV/NV relationship was significantly lower in the prealveolar and postalveolar bone grafting periods than in the normal population (P<0.01), confirming primary maxillary hypoplasia in patients with complete unilateral CLP. The CV/NV decreased progressively with worsening occlusal index classifications (P=0.03). No associations were observed between MSV and any of the studied variables.

Conclusion:

The complex anatomy of patients with complete unilateral CLP impairs treatment outcomes, and maxillary hypoplasia must be considered an important predictive factor.
A Novel Technique for Repairing Alveolar Clefts: Computer-Assisted Design With Posterior of Mandible Block Bone Grafts
Authors: Gao Yisu , Chen Kai , Li Nannan , Xu Dianhang , Pang Wanyu , Zhu Zihe , Wu Guomin
Published: August 2024

Objective:

Iliac cancellous bone graft is the gold standard for the treatment of alveolar clefts. However, the resorption rate of iliac cancellous bone is generally high. In this study, the authors propose a new method for repairing alveolar clefts using block bone grafts in the posterior region of the mandibular molar and the anterior margin of the ascending branch.

Methods:

Ten patients with a diagnosis of unilateral or bilateral alveolar cleft were collected. Block bone grafting between the posterior mandibular molar region and the inner and outer oblique lines of the anterior margin of the ascending branch was used to treat the alveolar synostosis. Preoperative, 1-week postoperative, and 6-month postoperative multislice spiral computed tomography scans of the patients were collected and analyzed for preoperative design and postoperative graft bone morphology using computer-assisted software tools, which were also required to measure the changes in the bone tissue density in the posterior mandibular bone extraction area.

Results:

At 6 months postoperatively, the mean bone resorption rate of the posterior mandibular bone grafts for cleft alveolar processes was 33.96% ± 11.23%. Bone tissue density in the posterior mandibular bone grafting area recovered to near preoperative levels at 6 months postoperatively.

Conclusion:

The novel method of bone grafting for the cleft alveolar process used in this paper is really effective. Postoperative posterior mandibular bone extraction did not cause sequelae such as mandibular bone defects or poor morphology in the patients. Computer-assisted design and three-dimensional printing technology helped to improve intraoperative bone grafting accuracy and postoperative assessment.
A Comprehensive Review of Bilobed Flaps in Nasal Reconstruction: Technique, Outcomes, and Considerations
Authors: Bennett Anne , Peters Victoria , Meade Anna , Thornton James
Published: August 2024

Purpose:

Reconstruction of nasal defects, particularly in the lower third of the nose, presents significant challenges due to the area’s complex 3-dimensional structure and thicker, more sebaceous skin. The bilobed flap, a double transposition flap, has been a popular method for addressing these nasal defects.

Methods:

This retrospective review examines a single surgeon’s experience with bilobed flaps for nasal reconstruction over the last 15 years. Demographics, defect characteristics, intraoperative details, postoperative complications, and revisionary procedures were documented, and univariate and multivariate logistic regression analyses were used to assess complication rate associations.

Results:

In all, 148 bilobed reconstructions were analyzed, with a mean patient age of 62.6 years and 46.0% male prevalence. The most common indication for the procedure was basal cell carcinoma following Mohs surgery, with the majority of the defects located on the lower third of the nose. The average defect size was 1.11 cm². Complications occurred in 52.0% of cases, including pincushioning, scar thickening, asymmetry, alar stenosis, and wound dehiscence. Reoperations and additional treatments such as dermabrasion, steroid injections, and laser therapy were frequently necessary to address these issues. Logistic regression analysis demonstrated significantly more postoperative complications when the defect was located on the lower third of the nose when compared with the upper two-thirds.

Conclusions:

While the bilobed flap can provide adequate skin coverage with perfect color match, it is associated with notable complications that impact esthetic outcomes. Proper patient selection and surgical technique are crucial for optimizing results.
Early Treatment of Cerebrospinal Fluid Leakage After Traumatic Injury Using Pedicled Autologous Fascia Flap
Authors: Gao Kaiming , Wang Hu , Guo Wenqiang
Published: August 2024

Objective:

This study aims to investigate the efficacy of early intervention in cerebrospinal fluid leakage following traumatic brain injury through the utilization of pedicled autologous fascia flaps.

Methods:

A retrospective case series, spanning from May 2021 to May 2022, analyzed 8 traumatic brain injury cases with concomitant cerebrospinal fluid leakage. Each patient underwent simultaneous brain surgery and transcranial repair of the cerebrospinal fluid leak, employing a pedicled autologous fascia flap. Clinical and imaging data were comprehensively recorded throughout the entire duration of the cases, and patient follow-ups were conducted through outpatient visits and telephone consultations.

Results:

The study comprised 8 enrolled patients, consisting of 7 males and 1 female, all of whom sustained injuries from traffic accidents. The mean age ranged from 17 to 55 years. Among the patients, three presented with acute epidural hematoma, three with simple concave fractures, and 2 with concave fractures accompanied by brain contusion. Frontal sinus fractures were observed in all cases. All surgical interventions were successful, with no instances of cerebrospinal fluid leakage postoperatively. In addition, none of the patients developed intracranial infections. At the conclusion of the follow-up period, recurrent cerebrospinal fluid leakage was not observed in any of the patients.

Conclusions:

In cases where surgical intervention is necessary for cerebrospinal fluid leakage resulting from anterior cranial base fractures, the application of pedicled autologous fascia flaps in the acute stage proves effective in repairing leaks at the anterior cranial base. This approach may contribute to a reduction in the incidence of intracranial infections, ultimately yielding satisfactory patient recovery.
Individual Differences in Cognition and Perception Predict Neural Processing of Speech in Noise for Audiometrically Normal Listeners
Authors: Shehabi Sana , Comstock Daniel C. , Mankel Kelsey , Bormann Brett M. , Das Soukhin , Brodie Hilary , Sagiv Doron , Miller Lee M.
Published: August 2024

Individuals with normal hearing exhibit considerable variability in their capacity to understand speech in noisy environments. Previous research suggests the cause of this variance may be due to individual differences in cognition and auditory perception. To investigate the impact of cognitive and perceptual differences on speech comprehension, 25 adult human participants with normal hearing completed numerous cognitive and psychoacoustic tasks including the Flanker, Stroop, Trail Making, Reading Span, and temporal fine structure (TFS) tests. They also completed a continuous multi-talker spatial attention task while neural activity was recorded using electroencephalography (EEG). The auditory cortical N1 response was extracted as a measure of neural speech encoding during continuous speech listening using an engineered “chirped-speech” (Cheech) stimulus. We compared N1 component morphologies of target and masker speech stimuli to assess neural correlates of attentional gains while listening to concurrently played short story narratives. Performance on cognitive and psychoacoustic tasks were used to predict N1 component amplitude differences between attended and unattended speech using multiple regression. Results show inhibitory control and working memory abilities can predict N1 amplitude differences between the target and masker stories. Interestingly, none of the cognitive and psychoacoustic predictors correlated with behavioral speech-in-noise listening performance in the attention task, suggesting that neural measures may be more sensitive measures of cognitive and auditory processing as compared to behavioral measures alone.

SIGNIFICANCE STATEMENT

These findings contribute to our understanding of how cognition affects the neural mechanisms of speech perception. Specifically, our results highlight the complex interplay between cognitive abilities and neural encoding of speech in challenging listening environments with multiple speakers. By incorporating these additional measures of cognition, we can achieve a more comprehensive understanding of an individual’s speech perception abilities, even in individuals with normal hearing. This approach could lead to earlier detection of hearing issues and more personalized interventions, ultimately enhancing communication outcomes for those with hearing difficulty.
Mouse olfactory system acts as anemo-detector and -discriminator
Authors: Mahajan Sarang , Tamboli Suhel , Das Susobhan , Bhattacharjee Anindya S. , Pardasani Meenakshi , Srikanth Priyadharshini , Marathe Shruti D. , Adlakha Avi , Ranjan Lavanya , Pandey Sanyukta , Abraham Nixon M.
Published: August 2024

Airflow detection while smelling is a fundamental requirement for olfaction, yet the mechanisms underlying such multimodal processing in the olfactory system remain unknown. We report here that mice can learn to accurately discriminate airflow with parallel processing of both mechanical and chemical stimuli revealed by modulated sniffing and refined calcium signaling in the olfactory bulb inhibitory network. Genetic perturbation of AMPAR function and optogenetic control bidirectionally shifted airflow discrimination learning pace, with contrasting phenotypes observed for odor learning, engagement of inhibitory circuits, and setting the optimal inhibition level for stimulus refinement. Multimodal odor-airflow stimuli at subthreshold levels enhanced learning, demonstrating that mechanical stimuli heighten olfactory perception. Our results, thus explain the multimodality of olfaction, and reveal an unexplored dimensionality of odor perception.
Handy divisions: Hand-specific specialization of prehensile control in bimanual tasks
Authors: Naik Anvesh , Ambike Satyajit
Published: August 2024

When hammering a nail, why do right-handers wield the hammer in the right hand? The dynamic dominance theory suggests a somewhat surprising answer. The two hands are specialized for different types of tasks: the dominant for manipulating objects, and the non-dominant for stabilizing objects. Right-handers wield the moving object with their right hand to leverage the skills of both hands. Functional specialization in hand use is often illustrated using examples of object manipulation. However, the dynamic dominance theory is supported by wrist kinematics rather than object manipulation data. Therefore, our goal was to determine whether this theory extends to object manipulation.

We hypothesized that hand-specific differences will be evident in the kinematics of hand-held objects and in the control of grip forces. Right-handed individuals held two instrumented objects that were coupled by a spring. They moved one object while stabilizing the other object in various bimanual tasks. They performed motions of varying difficulty by tracking predictable or unpredictable targets. The two hands switched roles (stabilization vs movement) in various experimental blocks. The changing spring length perturbed both objects. We quantified the movement performance by measuring the objects’ positions, and grip force control by measuring grip-load coupling in the moving hand and mean grip force in the stabilizing hand.

The right hand produced more accurate object movement, along with stronger grip-load coupling, indicating superior predictive control of the right hand. In contrast, the left hand stabilized the object better and exerted a higher grip force, indicating superior impedance control of the left hand. Task difficulty had a weak effect on grip-load coupling during object movement and no effect on mean grip force during object stabilization. These results suggest that dynamic dominance extends to object manipulation, though the weak effect of task difficulty on grip characteristics warrants further investigation.
Computational Analysis of Treatment Resistant Cancer Cells
Authors: Matov Alexandre
Published: August 2024

Introduction

Prostate cancer (PC), which is a disease driven by the activity of the androgen receptor (AR), is the most commonly diagnosed malignancy and despite advances in diagnostic and treatment strategies, PC is the second most common cause of cancer mortality in men (Bray et al., 2018). Taxane-based chemotherapy is the only chemotherapy that prolongs survival in metastatic PC patients (Petrylak et al., 2004; Tannock et al., 2004). At the cellular level, taxanes bind to and stabilize microtubules (MTs) inhibiting all MT-dependent intracellular pathways. MTs are highly dynamic polymers that stochastically switch between phases of growth, shrinkage, and pause (Jordan and Wilson, 2004). Altered MT dynamics endow cancer cells with both survival and migratory advantages (Mitchison, 2012). Taxanes inhibit MT dynamics and alter the spatial organization of the MT network, thereby inhibiting intracellular trafficking of molecular cargo critical for tumor survival. In PC specifically, taxanes inhibit transcriptional activity downstream of MT stabilization (Thadani-Mulero et al., 2012) and AR nuclear accumulation (Darshan et al., 2011; Zhu et al., 2010).

Methods

Different tubulin inhibitors, even from within the same structural class as the taxanes, affect distinct parameters of MT dynamics (Jordan and Wilson, 2004), yet the selection of taxane for chemotherapy is not based on the particular patterns of dynamic behavior of the MT cytoskeleton in individual patients. We envisage that systematic characterization using quantitative analysis of MT dynamics in PC patient cells expressing clinically relevant protein isoforms (Matov and Bacconi, 2024; Thoma et al., 2010), before and after treatment with each of the taxanes, will allow us to identify criteria for the selection of the most suitable drug combination at the onset of treatment.

Results

We link MT dynamics in the presence of AR variants and sensitivity/resistance to taxanes and connect fundamental research with clinically relevant concepts to elucidate cellular mechanisms of clinical response to taxanes and, thus, advance the customization of therapy. Our computational live-cell analysis addresses questions in the context of the inherent differences in MT homeostasis as a function of AR content in PC cells, the specific parameters of MT dynamics each of the taxanes affects, and how can this information be used to match endogenous patterns of MT dynamics with drug-modulated MT behavior.

Conclusions

We investigate whether the sensitivity to taxanes, evaluated by computational analysis of MTs, can be linked to gene expression correlated with AR and its variants, and whether the resistance to taxanes can be linked to the presence of a specific AR splice variant, and can we identify which of the taxanes will be most effective based on the endogenous patterns of MT dynamics.
Guard-cell phytosterol homeostasis is critical for proper stomatal development
Authors: Yen Chih-Chung , Hsu Ya-Wen , Leu Kuan-Chieh , Chen Sheau-Shyang , Chen Tzu-Yun , Juan Chien-Ta , Kuan Chi , Shaw Jei-Fu , Ho Chin-Min Kimmy , Jauh Guang-Yuh
Published: August 2024

Stomata regulate gas exchange and control water loss in response to the environmental stimuli and their distribution in the leaf epidermis is tightly regulated during development to ensure proper patterns. Although many studies have focused on the function of early stomatal lineage cells, little is known about the role of mature guard cells (GCs) in maintaining stomatal distribution. Here, we identified a previously uncharacterized enzyme, GDSL-type sterol esterase (GSEase), that is specifically expressed in mature guard cells and catalyzes lipid droplet-stored phytosterol ester degradation. Loss ofGSEasedecreased the level of free campesterol, a biosynthetic precursor of brassinosteroids (BRs), reduced BR level, and increased stomatal density in leaves, which could be further rescued by increasing the BR signaling. Furthermore, selectively reducing the BR response in GCs by utilizing the GSEase promoter-drivendet2-1, a mutation causing BR biosynthesis deficiency, resulted in an elevated stomatal count, as demonstrated ingseaseplants. These results indicate that GSEase plays a critical role in maintaining phytosterol homeostasis in GCs and the released phytosterols suppress the initiation of stomatal development in adjacent cells though the BR pathway.
Green Conversations: Harnessing Plant Communication to control growth light intensity
Authors: Stevens James , Davey Phillip , Kasznicki Piotr , Hofmann Tanja A , Lawson Tracy
Published: August 2024

Controlled Environment Agriculture (CEA) delivers increased crop production per unit land, contributing to resilient food systems amidst challenges of climate change, population growth and urbanization. However, high energy costs associated with lighting impose substantial barriers to the widespread adoption of CEA. While light is indispensable for growth, critically its utilization by crops throughout the photoperiod remains sub-optimal, reducing photosynthetic efficiency and wasting energy. Here we have developed and demonstrated a novel real-time plant bio-feedback system that enables crops to directly ‘communicate’ optimal lighting requirements. Continuous non- invasive monitoring of photochemistry elicited decreased demand for light by basil at the end of the photoperiod. Our innovative approach increased yield by 10% and reduced energy consumption per unit fresh mass by 18%, delivering a 201gCO2gFW-1reduction in carbon footprint. Application of this technique at scale can revolutionise resource management of CEA, reinvigorating the productivity, profitability and sustainability of this food industry.

Author Contributions

JS & TL: designed the experiments; JS, PD and PK: performed all physiology experiments and data acquisition and carried out data analyses. TL, JS, PD and TH wrote the MS and all authors commented on the MS.

One-sentence summary

Chlorophyll fluorescence measurements of photosynthetic efficiency can be used to control growth light intensity in real time, optimising crop performance and energy use.
Specific redox and iron homeostasis responses in the root tip of Arabidopsis upon zinc excess
Authors: Thiébaut Noémie , Richtmann Ludwig , Sarthou Manon , Persson Daniel P. , Ranjan Alok , Schloesser Marie , Boutet Stéphanie , Rezende Lucas , Clemens Stephan , Verbruggen Nathalie , Hanikenne Marc
Published: August 2024

Zinc (Zn) excess negatively impacts primary root growth in Arabidopsis. Yet, the effects of Zn excess on specific growth processes in the root tip remain largely unexplored.

Transcriptomics, ionomics and metabolomics were used to examine the specific impact of Zn excess on the root tip (RT) compared to the remaining root (RR).

Zn excess exposure resulted in shortened root apical meristem and elongation zone, with differentiation initiating closer to the tip of the root. Zn accumulated at a lower concentration in the RT than in RR. This pattern was associated with lower expression of Zn homeostasis and Fe deficiency response genes.

A distinct distribution of Zn and Fe in RT and RR was highlighted by Laser Ablation ICP-MS analysis.

Specialized Trp-derived metabolism genes, typically associated with redox and biotic stress responses, were specifically up-regulated in the RT upon Zn excess, among thosePhytoalexin Deficient 3(PAD3) encoding the last enzyme of camalexin synthesis. In roots of wild-type seedlings, camalexin concentration increased by 6-fold upon Zn excess and apad3mutant displayed increased Zn sensitivity and an altered ionome.

Our results indicate that distinct redox and iron homeostasis mechanisms are key elements of the response to Zn excess in the RT.
Defensive freezing sharpens threat-reward information processing during approach-avoidance decision making
Authors: Klaassen Felix H. , Bramson Bob , Schoffelen Jan-Mathijs , de Voogd Lycia D. , Roelofs Karin
Published: August 2024

People regularly face approach-avoidance dilemmas which require minimization of potential threat whilst maximizing potential reward. Defensive reactions to threat, such as transient states of freezing, influence integration of reward/threat information in the dorsal Anterior Cingulate Cortex (dACC). However, the mechanism of this integration between internal state and external value (state-value integration) remains unknown. Here, we decoded approach-avoidance decisions under threat using high-precision magnetoencephalography (MEG). Threat-induced cardiac deceleration (indicative of defensive freezing) was trial-by-trial associated with more pronounced effects of reward and threat magnitudes on approach-avoidance choices. Time-resolved decoding of threat-reward information from neural signals predicted approach-avoidance choices several seconds before the actual response. Crucially, during freezing, 6-12 Hz coherence between threat-reward information and dACC neural activity increased, suggesting that defensive freezing sharpens threat/reward processing during approach-avoidance decision making. These findings provide a potential neural mechanism by which threat-induced freezing can facilitate information integration, essential for optimal decision making under threat.
Natural genetic and transcriptomic variation in photosynthesis associated pathways contribute to adaptive traits variation in worldwideArabidopsis thalianapopulation
Authors: Liu Wei , Hou Jing , Liu Li , Lei Mengyu , Han Yu , Zhu Mingjia , Zhang Wenjia , Hao Ran , Ji Yan , Si Huan , Liu Jianquan , Zan Yanjun
Published: August 2024

Photosynthesis is the most important reaction underlying carbon fixation. Despite its potential in boosting carbon assimilation, nature variations underlying genes in photosynthesis pathway and their role in adaptive traits variation remains elusive. In this study, we investigated the genetic, transcriptomic variation of 1103 genes in photosynthesis associated pathways, including 82 photosynthesis core genes, 24 plastid-encoded RNA polymerase related genes, 2 nucleus-encoded RNA polymerase-related genes, 34 photomorphogenesis-related genes, 40 genes involved in transcription and translation (TAC) and 938 other nuclear-encoded chloroplast-targeted genes. Byde novoassembling the chloroplast genomes of 28 representative accessions and leveraging whole-genome, transcriptome sequencing data from the 1001 Genome Project, we revealed extensive natural genetic and transcriptome variations these genes in worldwideArabidopsis thalianapopulation. 34.0% of them were identified with regulatory variations in expression quantitative locus mapping (eQTL) mapping, including key components of Rubisco (RBCS1B, RBCS2B), and Rubisco activase (RCA). Genome-wide and transcriptome-wide association analysis (GWAS/TWAS) showed that these genetic and transcriptomic variations made considerable contribution to variation of adaptive traits. Overall, our study provides insight into the natural genetic variation of these genes among worldwideArabidopsis thalianaaccessions and their role in complex traits variation and adaptation.
The relationship between confidence and gaze-at-nothing oculomotor dynamics during decision-making
Authors: Cos Ignasi , Senel Gizem , Maldonado Pedro E. , Moreno-Bote Rubén
Published: August 2024

How does confidence relate to oculomotor dynamics during decision-making? Do oculomotor dynamics reflect deliberation and the buildup of confidence in the absence of visual stimuli? Here we examine the hypothesis that working memory, deliberation, and confidence warp oculomotor dynamics, both in the presence and absence of visual stimuli. We analyzed oculomotor dynamics in a decision-making task in which participants were provided with an abstract context in which to make the decision, and two similar option images which became eventually invisible. We show that fixations between the empty locations in which the images were formerly shown continued after the options disappeared, consistently with a sustained deliberative process facilitated by oculomotor dynamics. Both, oculomotor dynamics and decision patterns remained unchanged regardless of whether the stimuli were visible. Furthermore, our analyses show that the number of alternative fixations between stimuli correlated negatively with the confidence reported after each decision, while the observation time of the selected target correlated positively. Given that decisions in our experimental paradigm are reported in the absence of the stimuli, this suggests a relationship between evidence retrieval from working memory, confidence gathering and oculomotor dynamics. Finally, we performed a model comparison based on predictions from drift-diffusion models to assess the relationship between sequential fixations between images, deliberation and confidence gathering, and the ensuing choice. These analyses supported confidence as a contributing cognitive process encompassing serial evidence-gathering and parallel option consideration during decision-making.

One-Sentence Summary

The dynamics of oculomotor dynamics between absent stimuli are related with the participant’s confidence during value-based decision-making.
Response diversity is a major driver of temporal stability in complex food webs
Authors: Danet Alain , Kefi Sonia , Johnson Thomas Frederick , Beckerman Andrew P
Published: August 2024

Global change constitutes a suite of major threats to biodiversity and ecosystem functioning. These threats can materialise via changes in the temporal stability of ecological communities and the services they provide. However, the majority of research on stability has focused on single trophic level communities and has not yet integrated classic theory about species richness and food web structure with more recent theory centred on response diversity and stochasticity. Using a stochastic bioenergenetic food-web model, we reveal that response diversity is a major driver of community stability. Moreover, positive stability-richness relationships emerge only in the presence of response diversity. In contrast to previous work, food-web structural properties are only secondary drivers of overall community stability, but interact with response diversity to determine the sign of the stability-richness relationship. Our study highlights the complex pathways by which food-web structure and response diversity drive community stability, and raises concerns about how the loss of response diversity may lead to a breakdown of stability and the capacity for these communities to deliver functions and services to human societies.
Effect of sleep deprivation on fractal and oscillatory spectral measures of the sleep EEG: a window on basic regulatory processes
Authors: Horváth Csenge G. , Bódizs Róbert
Published: August 2024

Sleep is vital for sustaining life; therefore, reliable measurement of its regulatory processes is of significant importance in research and medicine. Here we examine the effect of extended wakefulness on the putative indicators of fundamental sleep regulatory processes (spectral slope and spindle frequency) proposed by the Fractal and Oscillatory Adjustment model of sleep regulation by involving a healthy young adult sample in a 35-hour long sleep deprivation protocol. Wearable headband EEG-derived results revealed that NREM sleep electroencephalogram (EEG) spectral slope estimated in the 2–48 Hz range is an accurate indicator of the predicted changes in sleep depth induced by sleep deprivation (steepened slopes in recovery sleep) or by the overnight dissipation of sleep pressure (flattening slopes during successive sleep cycles). While the baseline overnight dynamics of the center frequency of the sleep spindle oscillations followed a U-shaped curve, and the timing of its minimum (the presumed phase indicator) correlated with questionnaire-based chronotype metrics as predicted, a different picture emerged during recovery sleep. Advanced recovery sleep advanced the timing of the minima of the oscillatory spindle frequency, reduced considerably its relationship with chronotype, but retained partially its U-shaped overnight evolution. Overall, our study supports the use of the spectral slope of the sleep EEG as a homeostatic marker of wake-sleep regulation, in addition, encourages further research on the EEG-derived measure of the circadian rhythm, primarily focusing on its interaction with the homeostatic process.
De novodesign of Ras isoform selective binders
Authors: Zhang Jason Z. , Li Xinting , Batingana Alexa Rane , Liu Caixuan , Jiang Hanlun , Shannon Kevin , Huang Benjamin J. , Wu Kejia , Baker David
Published: August 2024

The proto-oncogene Ras which governs diverse intracellular pathways has four major isoforms (KRAS4A, KRAS4B, HRAS, and NRAS) with substantial sequence homology and similarin vitrobiochemistry. There is considerable interest in investigating the roles of these independently as their association with different cancers vary, but there are few Ras isoform-specific binding reagents as the only significant sequence differences are in their disordered and highly charged C-termini which have been difficult to elicit antibodies against. To overcome this limitation, we use deep learning-based methods tode novodesign Ras isoform-specific binders (RIBs) for all major Ras isoforms that specifically target the Ras C-terminus. The RIBs bind to their target Ras isoforms bothin vitroand in cells with remarkable specificity, disrupting their membrane localization and inhibiting Ras activity, and should contribute to dissecting the distinct roles of Ras isoforms in biology and disease.
Modelling the invasion, management strategies and economic impact of the invasive alien aquatic plantEgeria densa
Authors: Flores-García Adrián , Dobson John Y. , Fonfría Eva S. , García-García David , Bordehore Cesar
Published: August 2024

Egeria densa is a south American aquatic plant considered as an invasive alien species with a very aggressive and expansionist behaviour out of its native ecosystems. The widespread decorative use ofE. densain aquariums, coupled with the potential for subsequent disposal malpractice, has resulted in its introduction into a range of vulnerable ecosystems across the globe. This work presents a dynamic model of a population ofE. densabased on its accidental introduction into an ecosystem in southeastern Spain. The model allows the simulation of colonisation process and management and disposal strategies. The model considers the influence of environmental variables such as temperature, light and water turbidity on the growth of the species. Among the management strategies tested, the optimal appears to be those of a preventive nature before the plant spreads, given that the costs of removal will be very high at that stage, and with high ecological impacts.
Genetic regulation of nascent RNA maturation revealed by direct RNA nanopore sequencing
Authors: Choquet Karine , Chaumont Louis-Philippe , Bache Simon , Baxter-Koenigs Autum R. , Churchman L. Stirling
Published: August 2024

Quantitative trait loci analyses have revealed an important role for genetic variants in regulating alternative splicing (AS) and alternative cleavage and polyadenylation (APA) in humans. Yet, these studies are generally performed with mature mRNA, so they report on the outcome rather than the processes of RNA maturation and thus may overlook how variants directly modulate pre-mRNA processing. The order in which the many introns of a human gene are removed can substantially influence AS, while nascent RNA polyadenylation can affect RNA stability and decay. However, how splicing order and poly(A) tail length are regulated by genetic variation has never been explored. Here, we used direct RNA nanopore sequencing to investigate allele-specific pre-mRNA maturation in 12 human lymphoblastoid cell lines. We found frequent splicing order differences between alleles and uncovered significant single nucleotide polymorphism (SNP)-splicing order associations in 17 genes. This included SNPs located in or near splice sites as well as more distal intronic and exonic SNPs. Moreover, several genes showed allele-specific poly(A) tail lengths, many of which also had a skewed allelic abundance ratio.HLAclass I transcripts, which encode proteins that play an essential role in antigen presentation, showed the most allele-specific splicing orders, which frequently co-occurred with allele-specific AS, APA or poly(A) tail length differences. Together, our results expose new layers of genetic regulation of pre-mRNA maturation and highlight the power of long-read RNA sequencing for allele-specific analyses.
A simple MiMIC based approach for tagging endogenous genes to visualise live transcriptionin vivo
Authors: Beadle Lauren Forbes , Sutcliffe Catherine , Ashe Hilary L.
Published: August 2024

Live imaging of transcription in theDrosophilaembryo using the MS2 or PP7 systems is transforming our understanding of transcriptional regulation. However, insertion of MS2/PP7 stem loops into endogenous genes requires laborious CRISPR genome editing. Here we exploit the previously described Minos-mediated integration cassette (MiMIC) transposon system inDrosophilato establish a method for simply and rapidly inserting MS2/PP7 cassettes into any of the thousands of genes carrying a MiMIC insertion. In addition to generating a variety of stem loop donor fly stocks, we have made new stocks expressing the complementary coat proteins fused to different fluorescent proteins. We show the utility of this MiMIC-based approach by MS2/PP7 tagging and live imaging transcription of endogenous genes and the long non-coding RNA,roX1, in the embryo. We also present live transcription data from larval brains, the wing disc and ovary, thereby extending the tissues that can be studied using the MS2/PP7 system. Overall, this first high throughput method for tagging mRNAs inDrosophilawill facilitate the study of transcription dynamics of thousands of endogenous genes in a range ofDrosophilatissues.
Training Data Diversity Enhances the Basecalling of Novel RNA Modification-Induced Nanopore Sequencing Readouts
Authors: Wang Ziyuan , Liu Ziyang , Fang Yinshan , Zhang Hao Helen , Sun Xiaoxiao , Hao Ning , Que Jianwen , Ding Hongxu
Published: August 2024

Accurately basecalling sequence backbones in the presence of nucleotide modifications remains a substantial challenge in nanopore sequencing bioinformatics. It has been extensively demonstrated that state-of-the-art basecallers are less compatible with modification-induced sequencing signals. A precise basecalling, on the other hand, serves as the prerequisite for virtually all the downstream analyses. Here, we report that basecallers exposed to diverse training modifications gain the generalizability to analyze novel modifications. With synthesized oligos as the model system, we precisely basecall various out-of-sample RNA modifications. From the representation learning perspective, we attribute this generalizability to basecaller representation space expanded by diverse training modifications. Taken together, we conclude increasing the training data diversity as a novel paradigm for building modification-tolerant nanopore sequencing basecallers.
A Comparison of Skeletal Muscle Diffusion Tensor Imaging Tractography Seeding Methods
Authors: Damon Bruce M. , Guzman Roberto Pineda , Lockard Carly A. , Zhou Xingyu
Published: August 2024

The internal arrangement of a muscle’s fibers with respect to its mechanical line of action (muscle architecture) is a major determinant of muscle function. Muscle architecture can be quantified using diffusion tensor magnetic resonance imaging-based tractography, which propagates streamlines from a set of seed points by integrating vectors that represent the direction of greatest water diffusion (and by inference, the local fiber orientation). Previous work has demonstrated that tractography outcomes are sensitive to the method for defining seed points, but this sensitivity has not been fully examined. To do so, we developed a realistic simulated muscle architecture and implemented four novel methods for tract seeding: seeding along the muscle-aponeurosis boundary with an updated procedure for rounding seed points prior to lookup in the muscle boundary mask and diffusion tensor matrix (APO-3); voxel-based seeding throughout the muscle volume at a user-specified spatial frequency (VXL-1); voxel-based seeding throughout the muscle volume at a variable spatial frequency (VXL-2), and seeding near external and internal muscle boundaries (VXL-3). We then implemented these methods in an example human dataset. The updated aponeurosis seeding procedures allow more accurate and robust tract propagation from seed points. The voxel-based seeding methods had quantification outcomes that closely matched the updated aponeurosis seeding method. Further, the voxel-based methods can accelerate the overall workflow and may be beneficial in high throughput analysis of multi-muscle datasets. Continued evaluation of these methods in a wider range of muscle architectures is warranted.
Distinct functional domains of Dystroglycan regulate inhibitory synapse formation and maintenance in cerebellar Purkinje cells
Authors: Jahncke Jennifer N. , Schnell Eric , Wright Kevin M.
Published: August 2024

Dystroglycan is a cell adhesion molecule that localizes to synapses throughout the nervous system. While Dystroglycan is required to maintain inhibitory synapses from cerebellar molecular layer interneurons (MLIs) onto Purkinje cells (PCs) whether initial synaptogenesis during development is dependent on Dystroglycan has not been examined. We show that conditional deletion ofDystroglycanfrom Purkinje cells prior to synaptogenesis results in impaired MLI:PC synapse formation and function due to reduced presynaptic inputs and abnormal postsynaptic GABAAreceptor clustering. Using genetic manipulations that disrupt glycosylation of Dystroglycan or truncate its cytoplasmic domain, we show that Dystroglycan’s role in synapse function requires both extracellular and intracellular interactions, whereas synapse formation requires only extracellular interactions. Together, these findings provide molecular insight into the mechanism of inhibitory synapse formation and maintenance in cerebellar cortex.
Brain activity discriminates acoustic simulations of the same environment
Authors: Matten Viola G , Stirnberg Rüdiger , van de Par Steven , Ewert Stephan D , Flanagin Virginia L
Published: August 2024

In complex acoustic environments, sound localization involves the integration of numerous interrelated auditory and cognitive cues, making it challenging to understand their relationship to brain activity. Here, we use virtual acoustics to probe the brain’s response to auditory distance cues in a realistic environment. We developed a system to record the actual MRI environment, simulated the same room with different degrees of accuracy, then presented sounds at one of two locations in the room. We implemented a novel auditory fMRI sequence to record brain activity. Despite only minor differences in acoustics between the auralizations, it was possible to decode all three rooms from brain activity. A systematic analysis revealed that the direct-to-reverberant energy ratio (DRR) drove brain activity differences between auralizations, centered on the posterior auditory cortex (AC). The results provide strong evidence that the posterior AC processes DRR for spatial auditory perception.

Impact statement

A novel fMRI sequence and recording technique are combined with virtual acoustics and multi-variate analyses to decode room simulations from brain activity during distance perception and identify the auditory factors that drive the pattern of activity in the brain.