bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of Medicaid expansion on rates of carpal tunnel release: an interrupted time series analysis
Authors: Khouri Alexander N. , Benítez Trista M. , Ouyang Zhongzhe , Fahmy Joseph N. , Wang Lu , Chung Kevin C.
Published: April 2024

Background:

Medicaid expansion through the Affordable Care Act (ACA) has been associated with greater access and utilization of surgical services in underserved populations. However, its impact on use of hand surgical care is less understood. The purpose of this study was to evaluate the association between New York State adoption of the ACA and carpal tunnel release (CTR) procedural volume in Medicaid beneficiaries.

Methods:

We conducted a pooled cross-sectional analysis of patients who underwent CTR using the Healthcare Cost and Utilization Project New York State all-payer database (2010-2018). An interrupted time series (ITS) analysis using an autoregressive integrated moving average model estimated the immediate and long-term impact of Medicaid expansion in January 2014 on CTR procedural volume in Medicaid beneficiaries and uninsured individuals.

Results:

A total of 112,569 patients were included in the sample. After expansion, we observed an absolute increase of 6% in the share of CTR procedures provided to Medicaid beneficiaries. Policy implementation was associated with an immediate 1.81% increase (95% CI=0.0085, 0.0277; p<0.001) in the probability of Medicaid as the primary payer and an annual increase of 1.68% (95% CI=0.0134, 0.0202; p<0.001) after reform. ITS analysis found this resulted in 4,190 additional CTR procedures in Medicaid beneficiaries than predicted without expansion.

Conclusions:

Study results suggest New York’s adoption of the ACA was associated with an immediate and steady increase in use of outpatient CTR in Medicaid beneficiaries. Most of this increase represented newly treated patients rather than those who were previously uninsured.
High-Density Porous Polyethylene Implant Cranioplasty: A Systematic Review of Outcomes
Authors: Perozzo Filippo Andrea Giovanni , Ku Ying C. , Kshettry Varun R. , Sikder Prabaha , Papay Francis A. , Rampazzo Antonio , Bassiri Gharb Bahar
Published: April 2024

Porous polyethylene has been widely used in craniofacial reconstruction due to its biomechanical properties and ease of handling. The objective of this study was to perform a systematic review of the literature to summarize outcomes utilizing high-density porous polyethylene (HDPP) implants in cranioplasty. A literature search of PubMed, Cochrane Library, and Scopus databases was conducted to identify original studies with HDPP cranioplasty from inception to March 2023. Non-English articles, commentaries, absent indications or outcomes, and nonclinical studies were excluded. Data on patient demographics, indications, defect size and location, outcomes, and patient satisfaction were extracted. Summary statistics were calculated using weighted averages based on the available reported data. A total of 1089 patients involving 1104 cranioplasty procedures with HDPP were identified. Patients’ mean age was 44.0 years (range 2 to 83 y). The mean follow-up duration was 32.0 months (range 2 wk to 8 y). Two studies comprising 17 patients (1.6%) included only pediatric patients. Alloplastic cranioplasty was required after treatment of cerebrovascular diseases (50.9%), tumor excision (32.0%), trauma (11.4%), trigeminal neuralgia/epilepsy (3.4%), and others such as abscesses/cysts (1.4%). The size of the defect ranged from 3 to 340 cm2. An overall postoperative complication rate of 2.3% was identified, especially in patients who had previously undergone surgery at the same site. When data were available, contour improvement and high patient satisfaction were reported in 98.8% and 98.3% of the patients. HDPP implants exhibit favorable outcomes for reconstruction of skull defects. Higher complication rates may be anticipated in secondary cranioplasty cases.
Postsurgical Volumetric Airway Changes in Class III Patients Receiving Bimaxillary Orthognathic Surgery
Authors: Diker Nurettin , Cunha Giovanni , Salmen Fued Samir , Santana Eduardo , Gabrielli Mario
Published: April 2024

The purpose of the present study was to investigate the pharyngeal airway space (PAS) changes in class III patients receiving bimaxillary orthognathic surgery and correlate the PAS volume and minimum axial section changes with the magnitude of the surgical movement. This research involved a retrospective sample composed of 38 patients with class III skeletal occlusions. Three-dimensional measurements of the PAS volume and minimum axial section were conducted. Cephalometric points were used to verify the extent of jaw-hyoid bone movement. No significant differences were found between pre and postoperative total PAS volume (P = 0.280), nasopharyngeal volume (P = 0.545), oropharyngeal volume (P = 0.297), and minimum axial section (P = 0.568). Anterior movement of point A and posterior nasal spine were significantly associated with an increase in total PAS volume, oropharyngeal volume, and minimum axial section (P < 0.05). However, the posterior movement of menton was significantly associated with a decrease in total PAS volume, oropharyngeal volume, and minimum axial section (P < 0.05). The results of the present study indicated that PAS is not negatively affected by bimaxillary surgery in class III patients. However, the planning of class III patients who are prone to the development of airway problems should be done carefully.
Modified Endaural Approach With a Peripheral Dissection of the Superficial Musculoaponeurotic System to Access the Temporomandibular Joint to Prevent Facial Nerve Injury
Authors: Mejia Juan Pablo , Tabares Brandon Galviz , Geithner Carlos Miguel Ruiz
Published: April 2024

The purpose of this study was to assess the effects of protecting the facial nerve with a modified endaural approach with a peripheral dissection of the superficial musculoaponeurotic system to access the temporomandibular joint which allows an excellent operative field of visualization, multiple surgical procedures of the temporomandibular joint, and general care which improves the immediate postoperative period, making this a less morbid surgery. This study included 33 patients (39 sides) who underwent surgical treatment for disorders of the temporomandibular joint from the years 2021 to 2023 at the maxillofacial department of the clinic “Colsanitas” located in Bogota, Colombia. Therapeutic results were evaluated by postoperative facial nerve injury, with the House-Brackman scale; every patient was examined for adequate facial musculature function immediately after surgery. Notably, zero patients presented facial nerve injury. These results imply that the modified endaural approach with a peripheral dissection of the superficial musculoaponeurotic system to access the temporomandibular joint reduces the incidence of facial nerve injuries, improves operative site exposure, and lowers the frequency of complications.
Interventional Embolization of Unilateral Cavernous Sinus With ONXY Glue Combined With Coils for the Treatment of Bilateral Dural Arteriovenous Fistula
Authors: Li Wei , Liu Yang , Chu Fudi , Wang Yongli
Published: April 2024

Purpose:

To summarize the clinical experience of unilateral sponge sinus embolization of cavernous sinus dural arteriovenous fistula (CS DAVF) via jugular vein access with ONXY gel and spring coil intervention.

Methods:

The authors retrospectively analyzed the clinical data of 3 patients who were treated with unilateral cavernous sinus embolization for bilateral cavernous sinus dural arteriovenous fistula (CS DAVF) from October 2020 to May 2022 in our department by using transjugular vein access spring coil + ONXY gel interventional embolization.

Results:

Immediate postoperative angiography suggested that the cavernous sinus fistula was completely embolized in all 3 patients, and cerebral angiography was carried out from 6 to 12 months after the operation and assessed using the Class grading method, and there was no recurrence in any of the 3 patients.

Conclusions:

Transvenous access ONXY adhesive combined with spring coil interventional embolization of unilateral cavernous sinus to cure bilateral cavernous sinus dural arteriovenous fistula is feasible, which can avoid the excessive use of spring coils and ONXY adhesive, and it is the key to the effective cure of DAVF in cavernous sinus area and to reduce the complication.
Clinical Outcomes of a Large, Prospective Series of Gastric Electrical Stimulation Patients Using a Multidisciplinary Protocol
Authors: Cassidy Douglas J , Gerull William , Zike Valerie M , Awad Michael M
Published: April 2024

BACKGROUND:

Gastric electrical stimulation (GES) is an intervention used in the treatment of medically refractory gastroparesis. There are few large series demonstrating efficacy over a long-term follow-up period. This study reports clinical outcomes for patients from a single institution for up to 5 years.

STUDY DESIGN:

A prospective database of patients undergoing GES implantation for gastroparesis was collected and reviewed. Patients were selected according to a multidisciplinary institutional protocol. Baseline characteristics, including age, sex, smoking history, etiology of gastroparesis, and duration of gastroparesis symptoms, were collected. Symptomatic response was evaluated using Gastroparesis Cardinal Symptom Index (GCSI) surveys preoperatively and at subsequent follow-up visits. Other clinical outcome variables include medication use, hospitalizations due to gastroparesis, and overall satisfaction with symptom relief. Patient outcomes regarding reoperation and explantation were also recorded.

RESULTS:

A total of 157 patients have undergone GES at our institution since 2012. GCSI scores were collected in all patients at baseline, in 141 patients at 1-year follow-up, and in 110 patients at 5-year follow-up. Symptom severity in all 9 gastroparesis symptoms evaluated by the GCSI, as well as the total GCSI score, was reduced significantly at 1 year postoperatively, and these results were sustained at 5-year follow-up. Use of prokinetic and antiemetic medications was reduced during the follow-up period. Hospitalizations due to gastroparesis symptoms were also reduced. GES devices were explanted in 5 patients, 12 patients required generator exchanges, and 7 patients required reoperation due to displaced or eroded device leads during the study period.

CONCLUSIONS:

GES is associated with sustained symptomatic relief, reduced reliance on medications, and reduced hospitalizations in gastroparesis patients selected using our institutional protocol.
Phenotypic antibiotics susceptibility profile of clinical Enterobacteriaceae isolates from Kaduna State, North-west Nigeria
Authors: Ezeh Peace Amarachukwu , Olayinka Busayo Olalekan , Bolaji Rebecca Olajumoke , Suleiman Babangida Ahmed , Olowookere Ahmed
Published: April 2024

Background: The increasing resistance of clinical Enterobacteriaceae infection to commonly prescribed antibiotics have been reported around the world. Data is generally lacking on the prevalence and antibiotic susceptibility profile of clinical Enterobacteriaceae isolates from Kaduna, northwest Nigeria. This study thus aimed to determine the diversity of clinical Enterobacteriaceae isolates recovered from clinical specimens of patients admitted into two selected healthcare institutions in Kaduna, Nigeria.
Methods: Non-duplicate clinical bacteria isolates recovered from various specimens were collected and identified using rapid biochemical identification kits. The susceptibility of identified Enterobacteriaceae to various antibiotics and phenotypic detection of carbapenemase enzymes were thereafter determined.
Results:  Of the 500 collected bacterial isolates, 108 (21.6 %) were identified as Enterobacteriaceae, with Pantoea agglomerans (52, 48.1%), Klebsiella oxytoca (19, 17.6%) as the most prevalent. The isolates exhibited high resistance to azithromycin (69%) and ceftazidime (42%), while exhibiting low resistance to amikacin (7%) and imipenem (10%). Among the carbapenem-resistant Enterobacteriaceae (CRE) isolates, a significant proportion (66.6 %) tested positive for carbapenemase activity.
Conclusion: This study reports a high prevalence of multi-drug resistant Enterobacteriaceae in Kaduna, northwest Nigeria. The emergence of pathogenic P. agglomerans and an alarmingly high prevalence of carbapenemase-producing CRE are also observed. The presence of carbapenemase producers in an area with low carbapenem usage and resistance rates raises significant concerns. Continuous surveillance and robust antibiotic stewardship policies are imperative to preserve the efficacy of carbapenems in this region.
Relevance of Antibodies against the Chicken Anaemia Virus
Authors: Ingberman Max , Caron Luiz Felipe , Rigo Fernanda , Araujo Liliam C. , de Almeida Marco A.P. , Dal Bérto Letícia , Beirão Breno Castello Branco
Published: April 2024

Background

Chicken Infectious Anaemia (CIA) Virus (CAV) curtails the function of multiple immune compartments. Mortality due to blatant infection is controlled in broilers by passive immunization derived from vaccinated breeders. Therefore, chicks are often assessed by serology to determine maternally-derived antibodies (MDA).

Methods

A vaccine overdose-induced model of CIA. The model replicated the most common features of the disease. This model was used to determine the role of MDA in the protection of chicks. Hatchlings were tested for anti-CAV by ELISA and were sorted into groups based on antibody levels. SPF chicks were used as a no-antibody control.

Results

Lower specific antibody levels seemed to facilitate viral entry into the thymus, but viral levels, CD4+and CD8+counts, thymus architecture, and haematocrit were preserved by MDA, regardless of its levels.

Conclusion

Levels of MDA are not correlated with CIA, but are important for CAV infection.

IMPORTANCE

Vaccination is paramount in broiler production. Many of the vaccines are given to broiler breeders, instead of to the broilers themselves. This is cost-effective and practical, since in vaccinating one breeder hundreds of broilers are born with maternally-derived protection. To assess the quality of maternal immunity, antibodies are measured in their chicks. For Chicken Anaemia, this does not seem to suffice to verify protection. This viral disease is very common, and measuring maternal immunity against it determines whether to purchase chicks from a breeder farm. In this study, we verified that antibodies are not correlated with protection from the disease, and therefore should not be used as the sole parameter in assessing immunity against Chicken Anaemia in broilers.
Blind but alive - congenital loss ofatoh7disrupts the visual system of adult zebrafish
Authors: Hammer Juliane , Röppenack Paul , Yousuf Sarah , Machate Anja , Fischer Marika , Hans Stefan , Brand Michael
Published: April 2024

1

Purpose

Vision is the predominant sense in most animal species. Loss of vision can be caused by a multitude of factors resulting in anatomical as well as behavioral changes. In mice and zebrafish,atoh7mutants are completely blind as they fail to generate retinal ganglion cells during development. In contrast to mice, raising blind zebrafish to adulthood is challenging and this important model is currently missing in the field. Here, we report the phenotype of homozygous mutant adult zebrafishatoh7mutants that have been raised using adjusted feeding and holding conditions.

Methods

The phenotype of adult mutants was characterized using classical histology and immunohistochemistry as well as optical coherence tomography. In addition, the optokinetic response was characterized.

Results

Adultatoh7mutants display dark body pigmentation and significantly reduced body length. They fail to form retinal ganglion cells, the resulting nerve fiber layer as well as the optic nerve, and consequently behave completely blindly. In contrast, increased amounts of other retinal neurons and Müller glia are formed. In addition, the optic tectum is anatomically reduced in size, presumably due to the missing retinal input.

Conlusions

Taken together, we provide a comprehensive characterization of a completely blind adult zebrafish mutant with focus on retinal and tectal morphology, as a useful model for glaucoma and optic nerve aplasia.
Investigating the impact of lived experience stories on self-harm, mood, and help-seeking intentions: an experimental study
Authors: Ferrar Jennifer , Winstone Lizzy , Penton-Voak Ian , Biddle Lucy , Moran Paul , Grace Lydia , Mars Becky
Published: April 2024

Objective

To investigate the psychological impact of variations in help-seeking messages contained in lived experience stories about self-harm.

Method

In an online experiment, individuals with a recent history of self-harm, were randomised to read stories that either mentioned: i) self-help strategies, ii) seeking help from informal and formal sources, or iii) did not mention help-seeking. Help-seeking intentions, mood, entrapment, and expectations of future self-harm was measured, and participants provided feedback on the stories.

Results

There was limited evidence for an effect of story type on future help-seeking intentions and stronger evidence for an effect of story type on negative affect. Participants in the “Self-help” condition reported lower negative affect after reading the stories compared to participants in the “No help” condition (Mean difference = -3.97, 95% CI -7.72 to -0.22, p = .04) and the “Informal/formal” help condition (Mean difference = -3.70, 95% CI -7.55 to 0.14, p =.06). A key criticism of the stories was that they were unrelatable, but this sentiment was less prevalent among those in the “No help” condition. Key positives were that the stories included a realistic but hopeful outlook of recovery (less prevalent in the “Informal/formal help” condition) and were supportive (less prevalent in the “No help” condition).

Conclusion

While the inclusion of self-help strategies in a lived experience story reduced its impact on negative affect, the inclusion of self-help strategies or seeking help from others did not encourage future help-seeking intentions. Making stories relatable, authentic, and providing multiple strategies for support might be key to encourage help-seeking, but more research is needed.
How Do Neurotransmitter Pathways Contribute to Neuroimaging Phenotypes?
Authors: Ebneabbasi Amir , Afshani Mortaza , Seyed-Ahmadi Arman , Warrier Varun , Bethlehem Richard A.I. , Rittman Timothy
Published: April 2024

Neuroimaging could accurately reflect human behaviour in health and disease, but the mechanism by which image-derived phenotypes correspond to neurotransmitter systems remains uncertain. Prior studies have explored spatial correlations between neuroimaging phenotypes and positron emission tomography radiotracers. However, the influence of neurotransmitters goes beyond the receptors/transporters, influencing a wider array of intracellular components as pivotal parts of neurotransmitter pathways. Here, we used unsupervised learning to understand how the brain maps of healthy function (i.e., magnetoencephalography frequency-specific power) and abnormal structure (i.e., disorder-specific cortical thickness) are closely anchored to underlying neurotransmitter pathways assessed by gene expression data. To do this, we used large-scale datasets of the Human Connectome Project (HCP), Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) and Allen Human Brain Atlas (AHBA). We considered spatial and random gene null models to mitigate false positives. We replicate our analyses using different gene stability thresholds. This analytic approach paves the way for personalised medicine and advanced biomarkers.
Near-Infrared Afterglow Luminescence Amplification via Albumin Complexation of Semiconducting Polymer Nanoparticles for Surgical Navigation in Ex Vivo Porcine Models
Authors: Bendele Nathaniel , Kitamura Ken , Vasquez Isabella , Harun Asma , Carroll McKenzie , Srivastava Indrajit
Published: April 2024

Afterglow imaging, leveraging persistent luminescence following light cessation, has emerged as a promising modality for surgical interventions. However, the scarcity of efficient near-infrared (NIR) responsive afterglow materials, along with their inherently low brightness and lack of cyclic modulation in afterglow emission, has impeded their widespread adoption. Addressing these challenges requires a strategic repurposing of afterglow materials that improve on such limitations. Here, we have developed an afterglow probe, composed of bovine serum albumin (BSA) coated with an afterglow material, a semiconducting polymer dye (PFODBT/SP1), called BSA@SP1 demonstrating a substantial amplification of the afterglow luminescence (∼3-fold) compared to polymer-lipid coated PFODBT (DSPE-PEG@SP1) under same experimental conditions. This enhancement is believed to be attributed to the electron-rich matrix provided by BSA that immobilizes SP1 and enhances the generation of1O2radicals, which improves the afterglow luminescence brightness. Through molecule docking, physicochemical characterization, and optical assessments, we highlight BSA@SP1’s superior afterglow properties, cyclic afterglow behavior, long-term colloidal stability, and biocompatibility. Furthermore, we demonstrate superior tissue permeation profiling of afterglow signals of BSA@SP1’s compared to fluorescence signals usingex vivotumor-mimicking phantoms and various porcine tissue types (skin, muscle, and fat). Expanding on this, to showcase BSA@SP1’s potential in image-guided surgeries, we implanted tumor-mimicking phantoms within porcine lungs and conducted direct comparisons between fluorescence and afterglow-guided interventions to illustrate the latter’s superiority. Overall, our study introduces a promising strategy for enhancing current afterglow materials through protein complexation, resulting in both ultrahigh signal-to-background ratios and cyclic afterglow signals.
Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence
Authors: Zvolanek Kristina M. , Moore Jackson E. , Jarvis Kelly , Moum Sarah J. , Bright Molly G.
Published: April 2024

Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n=12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.
Developmental origins of Parkinson’s disease risk: perinatal exposure to the organochlorine pesticide dieldrin leads to sex-specific DNA modifications in critical neurodevelopmental pathways in the mouse midbrain
Authors: Kochmanski Joseph , Virani Mahek , Kuhn Nathan C. , Boyd Sierra L. , Becker Katelyn , Adams Marie , Bernstein Alison I.
Published: April 2024

Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson’s disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the α-synuclein preformed fibril (α-syn PFF) and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 weeks of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points – birth, 6 weeks, 12 weeks, and 36 weeks old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial-neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of DMCs with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period and disrupt critical neurodevelopmental pathways, thereby impacting risk of late life diseases, including PD.
Involvement of the cerebellum in structural connectivity enhancement in episodic migraine
Authors: Matoso Ana , Fouto Ana R , Esteves Inês , Ruiz-Tagle Amparo , Caetano Gina , da Silva Nuno A , Vilela Pedro , Gil-Gouveia Raquel , Nunes Rita G , Figueiredo Patrícia
Published: April 2024

Background

The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls.

Methods

To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM.

Results

We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine.

Conclusions

A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.
The molecular framework underlying the growth and defense tradeoff in Arabidopsis roots in response to danger signals
Authors: Dhar Souvik , Kim Soo Youn , Shin Heeji , Park Jongsung , Lee Ji-Young
Published: April 2024

Elevated stress signaling often compromises plant growth by suppressing proliferative and formative divisions at the meristem. Plant Elicitor Peptide 1 (PEP1), an endogenous danger signal triggered by both biotic and abiotic stresses in Arabidopsis thaliana, suppresses proliferative divisions, alters xylem vessel organizations, and disrupts cell-to-cell symplastic connections in the root. To gain an insight into the dynamic molecular framework that modulates root development under elevated danger signals, we performed a time course RNA-sequencing analysis at the root meristem following PEP1 treatment. A series of data analyses revealed that STZ and its homologs are a potential nexus between the stress response and proliferative cell cycle regulation. We observed that STZ differentially controls the cell cycle, cell differentiation, and stress response genes at various tissue layers in the root meristem through various functional, phenotypic, and transcriptomic analyses. Our study further indicated that the expression level of STZ in response to stresses is critically important to enable the growth and defense tradeoff. The findings here provide valuable information about the dynamic gene expression changes upon perceiving danger signals at the root meristem and future engineering schemes to generate stress-resilient plants.
Genetically encoded reporters of actin filament organization in living cells and tissues
Authors: Silva Martins Carla , Iv François , Kumar Suman Shashi , Panagiotou Thomas C. , Sidor Clara , Ruso-López María , Plancke Camille N. , Omi Shizue , Pagès Rebecca , Gomes Maxime , Llewellyn Alexander , Bandi Sourish Reddy , Ramond Laurie , Arbizzani Federica , Rimoli Caio Vaz , Schnorrer Frank , Robin François , Wilde Andrew , LeGoff Loïc , Pedelacq Jean-Denis , Jégou Antoine , Cabantous Stéphanie , Rincon Sergio A. , Chandre Cristel , Brasselet Sophie , Mavrakis Manos
Published: April 2024

The cytoskeletal protein actin is crucial for cell shape and integrity throughout eukaryotes. Actin filaments perform essential biological functions, including muscle contraction, cell division and tissue morphogenesis. These diverse activities are achieved through the ability of actin filaments to be arranged into precise architectures. Much progress has been made in defining the proteome of the actin cytoskeleton, but a detailed appreciation of the dynamic organizational state of the actin filaments themselves has been hindered by available tools. Fluorescence polarization microscopy is uniquely placed for measuring actin filament organization by exploiting the sensitivity of polarized light excitation to the orientation of fluorophores attached to actin filaments. By engineering fusions of five widely used actin localization reporters to fluorescent proteins with constrained mobility, we have succeeded in developing genetically-encoded, green- and red-fluorescent-protein-based reporters for non-invasive, quantitative measurements of actin filament organization in living cells and tissues by fluorescence polarization microscopy.
Cell wall-mediated maternal control of apical-basal patterning of the kelpUndaria pinnatifida
Authors: Dries Eloise , Meyers Yannick , Liesner Daniel , Gonzaga Floriele , Becker Jakob , Zakka Eliane E. , Beeckman Tom , Coelho Susana M , Clerck Olivier De , Bogaert Kenny A
Published: April 2024

The role of maternal tissue in the control of embryogenesis remains enigmatic in many complex organisms. Here, we investigate the contribution of maternal tissue to apical-basal patterning in the kelp embryo. Using a modified kelp fertilisation protocol which yields synchronously developing kelp embryos, we show that detachment from maternal tissue leads to compromised robustness of apical-basal patterning. Detached embryos are rounder and often show aberrant morphologies. Furthermore, absence of contact with maternal tissue increases parthenogenesis, highlighting the critical role of maternal signals in the initial stages of kelp development. When zygotes are detached from the female gametophyte while part of the oogonial cell wall still remains attached to the egg, the proper apical-basal patterning is rescued showing a key role for the connection to the maternal cell wall in developmental patterning in kelps. This observation is reminiscent of another brown alga,Fucus, where the cell wall has been shown to play a key role in cell fate determination. In the case of kelps, the maternal oogonium mediates basal cell fate determination by providing an extrinsic patterning cue in its extracellular matrix to the future embryo. Our findings suggest a conserved mechanism across phylogenetically distant oogamous brown algal lineages, where localised secretion of sulphated F2 fucans mediate establishment of the apical-basal polarity.
Delving into the claustrum: insights into memory formation, stabilization and updating in mice
Authors: Medina Candela , Ramos Santiago Ojea , Depino Amaicha M , Romano Arturo G , Krawczyk María C , Boccia Mariano M
Published: April 2024

The claustrum is a brain structure that remains shrouded in mystery due to the limited understanding of its cellular structure, neural pathways, functionality and physiological aspects. Significant research has unveiled connections spanning from the claustrum to the entire cortex as well as subcortical areas. This widespread connectivity has led to speculations of its role in integrating information from different brain regions, possibly contributing to processes such as attention, consciousness, learning and memory. Our working hypothesis posits that claustrum neural activity contributes to the formation, stabilization and updating of long-term memories in mice. We found evidence in CF-1 mice of a decline in behavioral performance in an inhibitory avoidance task due to intra-claustral administration of 2% lidocaine immediately after a training session or memory recall. Nevertheless, this does not seem to be the case for the acquisition or retrieval of this type of memory, although its neural activity is significantly increased after training, evaluated through c-Fos expression. Moreover, inhibition of the claustrum’s synaptic activity appears to impair stabilization but not the acquisition or retrieval of an unconditioned memory formed in a nose-poke habituation task.
Signal integration and integral feedback control with biochemical reaction networks
Authors: Andrews Steven S. , Kochen Michael , Smith Lucian , Feng Song , Wiley H. Steven , Sauro Herbert M.
Published: April 2024

Biochemical reaction networks perform a variety of signal processing functions, one of which is computing the integrals of signal values. This is often used in integral feedback control, where it enables a system’s output to respond to changing inputs, but to then return exactly back to some pre-determined setpoint value afterward. To gain a deeper understanding of how biochemical networks are able to both integrate signals and perform integral feedback control, we investigated these abilities for several simple reaction networks. We found imperfect overlap between these categories, with some networks able to perform both tasks, some able to perform integration but not integral feedback control, and some the other way around. Nevertheless, networks that could either integrate or perform integral feedback control shared key elements. In particular, they included a chemical species that was neutrally stable in the open loop system (no feedback), meaning that this species does not have a unique stable steady-state concentration. Neutral stability could arise from zeroth order decay reactions, binding to a partner that was produced at a constant rate (which occurs in antithetic control), or through a long chain of covalent cycles. Mathematically, it arose from rate equations for the reaction network that were underdetermined when evaluated at steady-state.
MooViE – Engine for single-view visual analysis of multivariate data
Authors: Stratmann Anton , Beyß Martin , Jadebeck Johann F. , Nöh Katharina
Published: April 2024

Understanding input-output relationships within multivariate datasets is an ubiquitous task in the life and data sciences. For this, visual analysis is indispensable for providing expressive summaries and preparing decision-making. We present the visual analysis approach and softwareMooViE, which is designed to strike the balance between being tailored to the specific data semantic and while being broadly applicable.MooViEsupports the data exploration process for extracting important information from the data and captures the result in a fresh single-view visualization.MooViEis implemented in C++ to facilitate fast access and effective interaction with comprehensive multivariate datasets. We showcase the engine for various application fields, relevant to the life sciences.

Availability and Implementation

The source code is available under MIT license athttps://jugit.fz-juelich.de/IBG-1/ModSim/MooViEandhttps://github.com/JuBiotechMooViE, with detailed documentation and usage instructions (https://moovie.readthedocs.io), as well as zenodo-archived releases (https://doi.org/10.5281/zenodo.10997388). Platform independent Docker images are also available (jugit-registry.fz-juelich.de/ibg-1/modsim/moovie/moovie).

Contact

Katharina Nöhk.noeh@fz-juelich.de
Enhancing cellular production of fucoxanthin through machine learning assisted predictive approach inIsochrysis galbana
Authors: Manochkumar Janani , Jonnalagadda Annapurna , Cherukuri Aswani Kumar , Vannier Brigitte , Janjaroen Dao , Ramamoorthy Siva
Published: April 2024

The marine microalgae,Isochrysis galbanais a prolific producer of fucoxanthin which is a xanthophyll carotenoid with substantial global market value boasting extensive applications in the food, nutraceutical, pharmaceutical, and cosmetic industries. Although supplementation of different phytohormones to medium enhances fucoxanthin production, the quantification of pigment by conventional means is time-consuming and labor-intensive. This study addressed the multiple methodological limitations of HPLC-based fucoxanthin quantification and emphasized the need to develop a Machine Learning (ML) model as optimization and precise prediction remain a challenging task. Hence, an integrated experimental approach coupled with ML models was employed to predict fucoxanthin yield by supplementation of various phytohormones. The accuracy of fucoxanthin prediction excluding and including hormone descriptors was compared and evaluated using the ML models namely Random Forest (RF), Linear Regression (LR), Artificial Neural Network (ANN), and Support Vector Machine (SVM). RF model provided the most accurate prediction excluding hormone descriptors with coefficient of determination (R2= 0.809) and root-mean-square error (RMSE= 0.776) followed by the ANN model with (R2= 0.722) and (RMSE= 0.937). The inclusion of hormone descriptors for training and pre-processing of data further improved the fucoxanthin prediction accuracy of the RF model to (R2= 0.839) and (RMSE= 0.712) and ANN model to (R2= 0.738) and (RMSE= 0.909). These results indicated that the combination of low-cost, Ultraviolet (UV) spectrometric-based fucoxanthin quantification coupled with ML algorithms can be efficiently used for reliable prediction and enhanced fucoxanthin production, therefore highlighting a promising approach and furnishing invaluable insights towards the commercialization of microalgal fucoxanthin production.
Structural and Dynamic Impacts of Single-atom Disruptions to Guide RNA Interactions within the Recognition Lobe of Geobacillus stearothermophilus Cas9
Authors: Belato Helen B , Knight Alexa L , D'Ordine Alexandra M , Pindi Chinmai , Fan Zhiqiang , Luo Jinping , Palermo Giulia , Jogl Gerwald , Lisi George P
Published: April 2024

The intuitive manipulation of specific amino acids to alter the activity or specificity of CRISPR-Cas9 has been a topic of great interest. As a large multi-domain RNA-guided endonuclease, the intricate molecular crosstalk within the Cas9 protein hinges on its conformational dynamics, but a comprehensive understanding of the extent and timescale of the motions that drive its allosteric function and association with nucleic acids remains elusive. Here, we investigated the structure and multi-timescale molecular motions of the recognition (Rec) lobe of GeoCas9, a thermophilic Cas9 from Geobacillus stearothermophilus. Our results provide new atomic details about the GeoRec subdomains (GeoRec1, GeoRec2) and the full-length domain in solution. Two rationally designed mutants, K267E and R332A, enhanced and redistributed micro-millisecond flexibility throughout GeoRec, and NMR studies of the interaction between GeoRec and its guide RNA showed that mutations reduced this affinity and the stability of the ribonucleoprotein complex. Despite measured biophysical differences due to the mutations, DNA cleavage assays reveal no functional differences in on-target activity, and similar specificity. These data suggest that guide RNA interactions can be tuned at the biophysical level in the absence of major functional losses, but also raise questions about the underlying mechanism of GeoCas9, since analogous single-point mutations have significantly impacted on- and off-target DNA editing in mesophilic S. pyogenes Cas9. A K267E/R332A double mutant did also did not enhance GeoCas9 specificity, highlighting the robust tolerance of mutations to the Rec lobe of GeoCas9 and species-dependent complexity of Rec across Cas9 paralogs. Ultimately, this work provides an avenue by which to modulate the structure, motion, and guide RNA interactions at the level of the Rec lobe of GeoCas9, setting the stage for future studies of GeoCas9 variants and their effect on its allosteric mechanism.
DMT1 contributes to MF- 438 - mediated inhibition of glioma cells
Authors: Zhang Laurence , Yamasaki Tomohiro , Dowdy Tyrone , Larion Mioara
Published: April 2024

Elevated SCD1 expression has been associated with enhanced cancer cell survival, proliferation, and resistance to therapy in many cancer types including gliomas. Hereby, we investigate the impact of MF-438 on SCD1-mediated lipid metabolism and its consequences on glioma growth and survival. Our data reveals an IDHmut-specific inhibitory effect of MF438 on gliomas. Also, we delineate a dual mechanism of action: while SCD1-mediated lipid metabolism is hindered by MF-438 treatment, MF-438 also exerts an SCD1-independent inhibition on DMT1 expression. Supporting data from the DMT1 blocker underscores its significance in MF-438’s anti-glioma efficacy.
Loss of spontaneous vasomotion precedes impaired cerebrovascular reactivity and microbleeds in a mouse model of cerebral amyloid angiopathy
Authors: Kozberg Mariel G , Munting Leon P , Maresco Lee H , Auger Corinne A , van den Berg Maarten L , Denis de Senneville Baudouin , Hirschler Lydiane , Warnking Jan M , Barbier Emmanuel L , Farrar Christian T , Greenberg Steven M , Bacskai Brian J , van Veluw Susanne J
Published: April 2024

Background

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease in which amyloid-β accumulates in vessel walls. CAA is a leading cause of symptomatic lobar intracerebral hemorrhage and an important contributor to age-related cognitive decline. Recent work has suggested that vascular dysfunction may precede symptomatic stages of CAA, and that spontaneous slow oscillations in arteriolar diameter (termed vasomotion), important for amyloid-β clearance, may be impaired in CAA.

Methods

To systematically study the progression of vascular dysfunction in CAA, we used the APP23 mouse model of amyloidosis, which is known to develop spontaneous cerebral microbleeds mimicking human CAA. Usingin vivo2-photon microscopy, we longitudinally imaged unanesthetized APP23 transgenic mice and wildtype littermates from 7 to 14 months of age, tracking amyloid-β accumulation and vasomotion in individual pial arterioles over time. MRI was used in separate groups of 12-, 18-, and 24-month-old APP23 transgenic mice and wildtype littermates to detect microbleeds and to assess cerebral blood flow and cerebrovascular reactivity with pseudo-continuous arterial spin labeling.

Results

We observed a significant decline in vasomotion with age in APP23 mice, while vasomotion remained unchanged in wildtype mice with age. This decline corresponded in timing to initial vascular amyloid-β deposition (∼8-10 months of age), although was more strongly correlated with age than with vascular amyloid-β burden in individual arterioles. Declines in vasomotion preceded the development of MRI-visible microbleeds and the loss of smooth muscle actin in arterioles, both of which were observed in APP23 mice by 18 months of age. Additionally, evoked cerebrovascular reactivity was intact in APP23 mice at 12 months of age, but significantly lower in APP23 mice by 24 months of age.

Conclusions

Our findings suggest that a decline in spontaneous vasomotion is an early, potentially pre-symptomatic, manifestation of CAA and vascular dysfunction, and a possible future treatment target.
Targeting oncogenic K-Ras mutants with a small-molecule degrader through Nedd4-1
Authors: Zeng Taoling , Jiang Tingting , Zhang Baoding , Zhang Ting , Dai Wanjun , Yin Xun , Li Yunzhan , Wu Caiming , Wu Yaying , Chi Ximin , Deng Xianming , Wang Hong-Rui
Published: April 2024

K-Ras mutations represent a most prevalent oncogenic alteration in human cancers. Despite of tremendous efforts, it remains a big challenge to develop inhibitors that can target the oncogenic K-Ras mutants, especially mutants without specific active or charged side chains such as K-RasG12V. Here, taking advantage of our previous finding that Nedd4-1 is a bona fide E3 ubiquitin ligase for wild-type Ras proteins, we developed a compound XMU-MP-9 that can promote ubiquitination and degradation of various K-Ras mutants including K-RasG12V, and significantly inhibit proliferation and tumor development of K-Ras mutant harboring cells. Mechanistically, XMU-MP-9 acts as a bifunctional compound to bind the C2 domain of Nedd4-1 and an allosteric site of K-Ras to enhance Nedd4-1 and K-Ras interaction, and to induce a conformational change of Nedd4-1/K-Ras complex to allow Nedd4-1 targeting K128 of K-Ras for ubiquitination. Hence, our study presents a robust strategy to develop small-molecule degrader of K-Ras mutants, and also sheds light on the development of small-molecule degraders for H-Ras and N-Ras mutants.