bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hawkmoth Proboscis: An Insect Model for Sensorimotor Control of Reaching and Exploration
Authors: Stöckl Anna , Deora Tanvi
Published: July 2024

Synopsis

Reaching and inspecting objects is an intricate part of human life, which is shared by a diversity of animals across phyla. In addition to appendages like legs and antennae, some insects use their mouthparts to reach and inspect targets. Hawkmoths of the family Sphingidae (Lepidoptera) use their extremely long and straw-like proboscis to drink nectar from flowers. As they approach flowers, hawkmoths uncoil their proboscis and explore the floral surface while hovering to target the proboscis to the nectary hole. Several sensory modalities provide feedback to control and guide these extremely versatile proboscis movements. The control task faced by the hawkmoths’ nervous system during such behaviors is not unlike that of an animal guiding limbs or a robotic agent guiding a manipulator to a target. Hawkmoths perform these reaching maneuvers while simultaneously hovering, and hence require rapid and continuous coordination between the proboscis, neck, and flight motor systems, thereby providing a unique invertebrate model for studying appendage guidance and reaching. Here, we review what is known about how hawkmoths use their proboscis for floral inspection and nectar discovery, as well as the role of various sensors in proboscis guidance. We give a brief overview of the morphology and muscular apparatus of the hawkmoth proboscis, and discuss how multimodal sensory feedback might be turned into motor action for appendage guidance.
Advanced hierarchical planning and design for low-carbon landscape architecture leveraging virtual reality technology
Authors: Zhu Fangda , Chen Yaling
Published: July 2024

The incorporation of sophisticated artificial intelligence technologies and data mining methodologies is critical for the planning and design of low-carbon landscape architectural environments. To enhance the three-dimensional reconstruction capabilities and visual esthetics of hierarchical planning and design within low-carbon landscape architectural environments, this study introduces a novel methodology predicated on virtual reality (VR) technology. This approach harnesses the diverse pictorial structure feature distribution inherent to low-carbon landscape architectural environments, amalgamated with VR's feature structure reorganization and enhancement techniques. Furthermore, we propose methodologies for joint measurement and multi-level integration to refine the hierarchical planning and design process within these environments. Simulation outcomes demonstrate the efficacy of this method in achieving superior three-dimensional reconstruction and visual representation, thereby augmenting the planning and design quality within the domain of low-carbon landscape architecture.
Research on the application of lightweight deep learning model in automatic identification of electricity-related public safety hazards in distribution lines
Authors: Feng Bin , Wei Jie
Published: July 2024

In view of the current problems of low speed, high network complexity, and difficulty in accurately detecting small target defects in insulator defect detection methods, this study proposes a lightweight insulator defect detection model. First, by enhancing both the convolutional block (CBL) and the efficient long-range aggregation network (ELAN-S) within the feature extraction network, the extraction capability for defect features is significantly augmented. Secondly, the CA-Tiny Spatial Pyramid Pooling (SPP) module was crafted by seamlessly integrating the coordinate attention mechanism with Tiny SPP, enabling the model to prioritize insulator defect characteristics and thereby enhancing defect detection accuracy. Finally, utilizing the positioning loss function WIoUv3 loss for loss calculation, a smaller gradient gain is assigned to low-quality anchor boxes, minimizing harmful gradients and enhancing the model’s positioning performance. Experimental outcomes demonstrate that the enhanced YOLOv7-tiny model excels in rapid and precise defect detection. In comparison to the original YOLOv7-tiny model, the proposed version is well-suited for edge device deployment, enabling real-time insulator defect detection.
H i content at cosmic noon – a millimetre-wavelength perspective
Authors: Messias Hugo , Guerrero Andrea , Nagar Neil , Regueiro Jack , Impellizzeri Violette , Orellana Gustavo , Vioque Miguel
Published: July 2024

In order to understand galaxy growth evolution, it is critical to constrain the evolution of its building block: gas. Mostly comprised by Hydrogen in its neutral (H i) and molecular (H$_2$) phases, the latter is the one mostly directly associated to star formation, while the neutral phase is considered the long-term gas reservoir. In this work, we make use of an empirical relation between dust emission at millimetre wavelengths and total gas mass in the interstellar medium (M$_{\rm HI}$ plus M$_{\rm H_2}$) in order to retrieve the H i content in galaxies. We assemble an heterogeneous sample of 335 galaxies at $0.01\lt z\lt 6.4$ detected in both mm-continuum and carbon monoxide (CO), with special focus on a blindly selected sample to retrieve H i cosmological content when the Universe was $\sim 2-6\,$ Gyr old ($1\lt z\lt 3$). We find no significant evolution with redshift of the M$_{\rm HI}$/M$_{\rm H_2}$ ratio, which is about $1-3$ (depending on the relation used to estimate M$_{\rm HI}$). This also shows that M$_{\rm H_2}$-based gas depletion times are underestimated overall by a factor of $2-4$. Compared to local Universe H i mass functions, we find that the number density of galaxies with M$_{\rm HI}\gtrsim 10^{10.5}\,$M$_\odot$ significantly decreased since 8–12 Gyr ago. The specific sample used for this analysis is associated to 20–50 per cent of the total cosmic H i content as estimated via Damped Lyman-$\alpha$ Absorbers. In IR luminous galaxies, H i mass content decreases between $z\sim 2.5$ and $z\sim 1.5$, while H$_2$ seems to increase. We also show source detection expectations for SKA surveys.
The PARSEC view of star formation in galaxy centres: from protoclusters to star clusters in an early-type spiral
Authors: Prieto Almudena , Gladis Magris C , Bruzual Gustavo , Fernández-Ontiveros Juan A , Burkert Andreas
Published: July 2024

Understanding star formation in galaxies requires resolving the physical scale on which star formation often occurs: the scale of star clusters. We present a multiwavelength, eight-parsec resolution study of star formation in the circumnuclear star cluster and molecular gas rings of the early-type spiral NGC 1386. The cluster ring formed simultaneously ∼4 Myr ago. The clusters have similar properties in terms of mass and star formation rate, resembling those of H ii regions in the Milky Way disc. The molecular CO gas resolves into long filaments, which define a secondary ring detached from the cluster ring. Most clusters are in CO voids. Their separation with respect to the CO filaments is reminiscent of that seen in galaxy spiral arms. By analogy, we propose that a density wave through the disc of this galaxy may have produced this gap in the central kpc. The CO filaments fragment into strings of dense, unresolved clouds with no evidence of a stellar counterpart. These clouds may be the sites of a future population of clusters in the ring. The free-fall time of these clouds, ∼10 Myr, is close to the orbital time of the CO ring. This coincidence could lead to a synchronous bursting ring, as is the case for the current ring. The inward spiralling morphology of the CO filaments and co-spatiality with equivalent kpc-scale dust filaments are suggestive of their role as matter carriers from the galaxy outskirts to feed the molecular ring and a moderately active nucleus.
Adaptation of the protein misfolding cyclic amplification (PMCA) technique for the screening of anti‐prion compounds
Authors: Do Katherine , Benavente Rebeca , Catumbela Celso S. G. , Khan Uffaf , Kramm Carlos , Soto Claudio , Morales Rodrigo
Published: July 2024

Prion diseases result from the misfolding of the physiological prion protein (PrPC) to a pathogenic conformation (PrPSc). Compelling evidence indicates that prevention and/or reduction of PrPSc replication are promising therapeutic strategies against prion diseases. However, the existence of different PrPSc conformations (or strains) associated with disease represents a major problem when identifying anti‐prion compounds. Efforts to identify strain‐specific anti‐prion molecules are limited by the lack of biologically relevant high‐throughput screening platforms to interrogate compound libraries. Here, we describe adaptations to the protein misfolding cyclic amplification (PMCA) technology (able to faithfully replicate PrPSc strains) that increase its throughput to facilitate the screening of anti‐prion molecules. The optimized PMCA platform includes a reduction in sample and reagents, as well as incubation/sonication cycles required to efficiently replicate and detect rodent‐adapted and cervid PrPSc strains. The visualization of PMCA products was performed via dot blots, a method that contributed to reduced processing times. These technical changes allowed us to evaluate small molecules with previously reported anti‐prion activity. This proof‐of‐principle screening was evaluated for six rodent‐adapted prion strains. Our data show that these compounds targeted either none, all or some PrPSc strains at variable concentrations, demonstrating that this PMCA system is suitable to test compound libraries for putative anti‐prion molecules targeting specific PrPSc strains. Further analyses of a small compound library against deer prions demonstrate the potential of this new PMCA format to identify strain‐specific anti‐prion molecules. The data presented here demonstrate the use of the PMCA technique in the selection of prion strain‐specific anti‐prion compounds.
To the Brain and Beyond: Neurological Implications of Glucagon-Like Peptide-1 Receptor Agonists
Authors: Hunter Guevara Lindsay R. , Beam W. Brian B. , Pasternak Jeffrey J.
Published: July 2024

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an increasingly popular class of medications commonly used for glycemic control in patients with type 2 diabetes mellitus and for weight loss. GLP-1 RAs also have potential benefits in patients with various neurological diseases independent of their glucose-modulating effect. In this focused review, we explore animal and clinical evidence evaluating the impact of GLP-1 RAs in common neurological diseases. Our aim is to provide a basis for hypothesis generation for future studies to assess the role that GLP-1 RAs may have on the nervous system, including implications for the perioperative period.
Concept of Double-eyelid Segments Ratio: Practical Application in Asian Blepharoplasty
Authors: Chen William P. D.
Published: July 2024

Background:

There have been few articles on the vertical dimension of the Asian upper eyelid, the eyelid crease segment, and the upper palpebral segment. The eyelid crease height manifests differently depending on whether it is closed (on extreme downgaze), open, or on upward gaze. This study will investigate a ratio practical for use in Asian blepharoplasty (external incisional method).

Methods:

The central vertical dimensions of Asian upper eyelids were measured, together with the upper palpebral segment and eyelid crease height when present. These parameters were recorded preoperatively and following double-eyelid surgery, and remeasured at 1 week and 2 months postoperative with eyelids closed and with eyes open looking straight ahead. The ratios of anatomic upper/lower segments and apparent (eyes opened) upper/lower ratio were tabulated for each case.

Results:

The mean vertical height of upper eyelid skin among Asian women 30 years of age and younger was 23.4 mm, and between 31 and 50 years of age was 25.4 mm. The design of Asian upper eyelid crease and determination of skin tissues that can be safely removed include designing crease height to be 7 mm or slightly less and leaving an upper eyelid segment of at least a length 2 times or more of the crease height, to yield an aesthetically desirable double-eyelid segments ratio.

Conclusions:

The study confirms the practical application of the upper/lower segments ratio at surgery and at full recovery (2 mo) using such technique and shows its progression to a desirable range of double-eyelid segments ratio. It has proven effective and useful for patients seeking Asian blepharoplasty.
Corneal High-Order Aberrations in Fuchs Endothelial Corneal Dystrophy and Subclinical Corneal Edema
Authors: Blöck Louise , Son Hyeck-Soo , Köppe Maximilian K. , Friedrich Maximilian , Auffarth Gerd U. , Augustin Victor A.
Published: July 2024

Purpose:

High-order aberrations (HOAs) are known to be increased in corneas with Fuchs endothelial dystrophy (FECD) and are associated with visual impairment. This case series aimed to analyze whether tomographic changes in FECD affect the HOA in the early period of the disease.

Methods:

In this retrospective single-center case series, 144 eyes of 85 patients were included, of which 78 eyes of 47 patients with FECD with slit-lamp biomicroscopically visible guttae but no visible corneal edema served as the study-cohort. According to Sun et al, included eyes were divided into 2 groups: group 0 (n = 28; no subclinical corneal edema) and group 1 (n = 50; subclinical corneal edema). A total of 66 healthy eyes of 38 patients served as control group. Mean values and standard deviations were calculated for the root mean square (RMS), coma, trefoil and spherical aberrations (SA) of the cornea (C), the anterior surface (CF), and the posterior surface (CB).

Results:

Statistically significant differences (P < 0.001) in the RMS HOA (group 0: 0.209 ± 0.044 μm, group 1: 0.372 ± 0.122 μm) and in coma (group 0: 0.082 ± 0.054 μm, group 1: 0.214 ± 0.101 μm) and SA (group 0: −0.130 ± 0.038 μm, group 1: −0.176 ± 0.074 μm) of the CB were found in eyes in group 1 versus those in group 0. There were no statistically significant differences in HOA between the control group and eyes in group 0.

Conclusions:

FECD eyes with subclinical corneal edema demonstrated significant increase in RMS, coma, and SA of the CB. Tomographic analysis, therefore, helps in visual impairment assessment, disease progression, and decision-making for early endothelial keratoplasty in patients with FECD.
Determining Risk Factors for Detachment After Endothelial Keratoplasties: Nine-Year Review of a Single Institution
Authors: Mian Osamah , Warmath Jacob , Refai Fares , Sandhu Umar , Multani Karan , Raj Anushka , Dvorak Justin , Murphy David A. , Riaz Kamran M.
Published: July 2024

Purpose:

To determine roles of patient history, donor tissue characteristics, tissue preparation methods, and surgeon technique for graft detachment requiring rebubbling after Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures.

Methods:

Retrospective analysis of all eyes undergoing first-time DSAEK or DMEK at the study institution between 2013 and 2022. Data were collected regarding recipients' history, donors’ medical history, tissue preparation methods, intraoperative details, and postoperative clinical outcomes. Multivariate statistical analysis was conducted to identify risk factors for graft detachment necessitating rebubbling.

Results:

Of 1240 eyes meeting inclusion criteria, 746 (60.2%) underwent DSAEK, and 494 (39.8%) underwent DMEK. DSAEK procedures had 12.5% rebubbling rate, whereas DMEK procedures had 18.4% rebubbling rate (P = 0.005). Sub50-DSAEK (<50 μm) grafts had 16.0% rebubble rate, whereas sub100-DSAEK (51–99 μm) and >100 μm DSAEKs had rebubble rate of 9.9% and 9.5%, respectively (P = 0.006). Significant risk factors for DSAEK graft detachment included history of retinal surgery (OR = 2.59), preloaded tissue (OR = 2.70), forceps insertion (OR = 2.33), use of sub50-DSAEK lenticules versus sub100-DSAEK (OR = 2.44) and >100 μm DSAEK (OR = 2.38) lenticules, and donor history of noninsulin-dependent diabetes mellitus (OR = 4.18). DMEK risk factors included recipient history of cancer (OR = 2.51) and use of higher SF6 gas concentration (OR = 1.09). Although rebubbled DMEK eyes had comparable refractive outcomes to nonrebubbled eyes (P >0.05), rebubbled DSAEK eyes had worse refractive outcomes at all time points (P < 0.05).

Conclusions:

Graft detachments in DSAEK and DMEK are influenced by various factors, including donor tissue characteristics, tissue preparation, and surgical technique. Identifying and understanding these factors can potentially improve postoperative outcomes.
A Possible Role of P-Cresyl Sulfate and Indoxyl Sulfate as Biomarkers in the Prediction of Renal Function According to the GFR (G) Categories
Authors: Corradi Valentina , Caprara Carlotta , Barzon Elena , Mattarollo Cecilia , Zanetti Fiammetta , Ferrari Fiorenza , Husain-Syed Faeq , Giavarina Davide , Ronco Claudio , Zanella Monica
Published: July 2024

Background:

Gut dysbiosis has been implicated in the development and progression of chronic kidney disease (CKD) by the generation of uremic toxins, such as the protein-bound solutes p-cresyl sulfate (pCS) and indoxyl sulfate (IXS). In this study, we evaluate the associations of total (t) and free fractions (f) of pCS and IXS with the Kidney Disease: Improving Global Outcomes (KDIGO) glomerular filtration rate (GFR; G) categories using contemporary GFR estimation equations.

Methods:

Liquid chromatography/tandem mass spectrometry has been applied for the identification and quantification of pCS and IXS.

Results:

We evaluated 80 patients (55 ± 13 years); 41 male. We found a statistically significant increase of pCSt, pCSf, IXSt and IXSf across the CKD spectrum as defined by GFR categories (P < 0.001). A significant negative correlation was observed between estimated glomerular filtration rate (eGFR, any equations) and plasma concentrations of pCS and IXS (all P values < 0.001). For example we reported correlation between eGFR 2021 Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI and pCSt (Spearman’s coefficient Rho [r] = -0.690), pCSf (r = -0.744), IXSt (r = -0.754) and IXSf (r = -0.819).

Conclusion:

We found that the free fraction as well as total concentrations of pCS and IXS were negatively correlated with estimated GFR (all equations) in CKD patients. The significant increase of pCS and of IXS across the CKD spectrum suggests that both protein-bound solutes may be used as surrogate markers of renal function.
Insight Into Severe Neonatal COVID-19 Gained Through Whole Exome Sequencing of Twin Neonates
Authors: Godwin Jennie , Daniel John , Chavez-Bueno Susana , Sampath Venkatesh
Published: July 2024

The genetic basis of neonatal COVID-19 infection, which exhibits a range of severity, has not been investigated. We identified both shared and unique genetic variants involved in antiviral immune responses through whole exome sequencing of an infant who developed severe COVID-19 pneumonia and multisystem inflammatory syndrome and the twin brother also positive for severe acute respiratory syndrome-coronavirus-2, but with only moderate respiratory symptoms.
The interplay between gut microbiome and physical exercise in athletes
Authors: Quaresma Marcus Vinicius L. dos Santos , Mancin Laura , Paoli Antonio , Mota João Felipe
Published: July 2024

Purpose of review

The gut microbiome regulates several health and disease-related processes. However, the potential bidirectional relationship between the gut microbiome and physical exercise remains uncertain. Here, we review the evidence related to the gut microbiome in athletes.

Recent findings

The effect of physical exercise on the intestinal microbiome and intestinal epithelial cells depends on the type, volume, and intensity of the activity. Strenuous exercise negatively impacts the intestinal microbiome, but adequate training and dietary planning could mitigate these effects. An increase in short-chain fatty acids (SCFAs) concentrations can modulate signaling pathways in skeletal muscle, contributing to greater metabolic efficiency, preserving muscle glycogen, and consequently optimizing physical performance and recovery. Furthermore, higher SCFAs concentrations appear to lower inflammatory response, consequently preventing an exacerbated immune response and reducing the risk of infections among athletes. Regarding dietary interventions, the optimal diet composition for targeting the athlete's microbiome is not yet known. Likewise, the benefits or harms of using probiotics, synbiotics, and postbiotics are not well established, whereas prebiotics appear to optimize SCFAs production.

The intestinal microbiome plays an important role in modulating health, performance, and recovery in athletes. SCFAs appear to be the main intestinal metabolite related to these effects. Nutritional strategies focusing on the intestinal microbiome need to be developed and tested in well controlled clinical trials.
Extensive loss of forage diversity in social bees owing to flower constancy in simulated environments
Authors: Grüter Christoph , Segers Francisca H. I. D. , Hayes Lucy
Published: July 2024

Many bees visit just one flower species during a foraging trip, i.e. they show flower constancy. Flower constancy is important for plant reproduction but it could lead to an unbalanced diet, especially in biodiversity-depleted landscapes. It is assumed that flower constancy does not reduce dietary diversity in social bees, such as honeybees or bumblebees, but this has not yet been tested. We used computer simulations to investigate the effects of flower constancy on colony diet in plant species-rich and species-poor landscapes. We also explored if communication about food sources, which is used by many social bees, further reduces forage diversity. Our simulations reveal an extensive loss of forage diversity owing to flower constancy in both species-rich and species-poor environments. Small flower-constant colonies often discovered only 30–50% of all available plant species, thereby increasing the risk of nutritional deficiencies. Communication often interacted with flower constancy to reduce forage diversity further. Finally, we found that food source clustering, but not habitat fragmentation impaired dietary diversity. These findings highlight the nutritional challenges flower-constant bees face in different landscapes and they can aid in the design of measures to increase forage diversity and improve bee nutrition in human-modified landscapes.
Enhancing the Positive Predictive Value of EGD for Diagnosis of Barrett’s Esophagus Through EsoGuard® Triage
Authors: Kurland Jayde E. , Patel Sheena B. , Englehardt Richard , Dezfoli Seper , Tseng Daniel M. , Foutz Michael W. , Bradley Paul S. , Eghterafi Badi , Lee Victoria T. , Verma Suman , deGuzman Brian J. , Aklog Lishan
Published: July 2024

Background

Guidelines support Barrett’s esophagus (BE) screening, but most eligible patients do not undergo endoscopic evaluation; non-endoscopic strategies are now supported as a reasonable alternative by U.S gastroenterology societies. EsoGuard (EG) is a DNA assay used with EsoCheck, a non-endoscopic cell collection device for detection of BE, which can be utilized as a triage to esophagogastroduodenoscopy (EGD) in patients meeting screening criteria. In doing so, EG may serve to enrich the population undergoing EGD, resulting in more BE diagnoses while potentially reducing utilization of already-limited endoscopy resources.

Aim

To test the hypothesis that BE detection in EGDs performed on EG positive patients will be significantly higher than the positive predictive value (PPV) of screening EGD alone.

Methods

Real-world data was retrospectively collected from EG positive patients for whom EGD diagnoses were available. Baseline patient characteristics, risk factors, and EGD results were obtained from the treating physicians. PPV of screening EGDs was the comparator and estimated by literature-established disease prevalence of BE, which in the U.S gastroesophageal reflux disease population is ∼10.6%. The hypothesis was tested using t-tests for single proportions at a one-sided 5% significance level.

Results

Data from 209 patients found 60 (28.7%) subjects with salmon-colored mucosa on EGD and specialized intestinal metaplasia on histopathology. However, 10 (4.8%) had < 1cm of disease on visual inspection, therefore, did not meet the American College of Gastroenterology definition of BE so was excluded from the analysis. Of the remaining 199 patients, 50 (25.1%) had BE on EGD. In the cohort of patients meeting ACG screening criteria, 28.9% (33/114) had BE. Overall, a 2.4-fold increase in BE detection was observed compared to the PPV of screening EGD, and in the ACG cohort this increase was 2.7-fold. Among ACG patients ≥65 years old, the increase was nearly 2.5-fold (25.9% detection rate).

Conclusions

Our data suggests EG and EC used as a triage test enriches the population undergoing EGD for BE, and compared to screening EGD alone, can help direct more efficient use of endoscopy resources to unburden the system without reducing the number of eligible patients screened and diagnosed.
Quantitative PET imaging and modeling of molecular blood-brain barrier permeability
Authors: Chung Kevin J. , Abdelhafez Yasser G. , Spencer Benjamin A. , Jones Terry , Tran Quyen , Nardo Lorenzo , Chen Moon S. , Sarkar Souvik , Medici Valentina , Lyo Victoria , Badawi Ramsey D. , Cherry Simon R. , Wang Guobao
Published: July 2024

Blood-brain barrier (BBB) disruption is involved in the pathogenesis and progression of many neurological and systemic diseases. Non-invasive assessment of BBB permeability in humans has mainly been performed with dynamic contrast-enhanced magnetic resonance imaging, evaluating the BBB as a structural barrier. Here, we developed a novel non-invasive positron emission tomography (PET) method in humans to measure the BBB permeability of molecular radiotracers that cross the BBB through different transport mechanisms. Our method uses high-temporal resolution dynamic imaging and kinetic modeling to jointly estimate cerebral blood flow and tracer-specific BBB transport rate from a single dynamic PET scan and measure the molecular permeability-surface area (PS) product of the radiotracer. We show our method can resolve BBB PS across three PET radiotracers with greatly differing permeabilities, measure reductions in BBB PS of18F-fluorodeoxyglucose (FDG) in healthy aging, and demonstrate a possible brain-body association between decreased FDG BBB PS in patients with metabolic dysfunction-associated steatotic liver inflammation. Our method opens new directions to efficiently study the molecular permeability of the human BBBin vivousing the large catalogue of available molecular PET tracers.
Sleep duration irregularity and risk for incident cardiovascular disease in the UK Biobank
Authors: Huang Tianyi , Kianersi Sina , Wang Heming , Potts Kaitlin S. , Noordam Raymond , Sofer Tamar , Rutter Martin K. , Redline Susan
Published: July 2024

Background

Emerging evidence supports a link between circadian disruption as measured by higher night-to-night variation in sleep duration and increased risk of cardiovascular disease (CVD). It remains unclear whether this association varies by CVD types or may be modified by average sleep duration and genetic risk for CVD.

Methods

Our prospective analysis included 86,219 UK Biobank participants who were free from CVD when completing 7 days of accelerometer measurement in 2013-2016. Sleep irregularity was evaluated by the standard deviation (SD) of accelerometer-measured sleep duration over 7 days. Incident major CVD events, defined as fatal or nonfatal myocardial infarction (MI) and stroke, were identified through linkage to Hospital Episode Statistics data until May 31, 2022. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs for associations of sleep duration SD with risk for major CVD events overall and for MI and stroke separately.

Results

We documented 2,310 incident cases of major CVD events (MI: 1,183, stroke: 1,175) over 636,258 person-years of follow-up. After adjusting for sociodemographic factors and family history of CVD, the HR (95% CI) associated with a 1-hour increase in sleep duration SD was 1.19 (1.10, 1.27) for CVD (p-trend<0.0001), 1.23 (1.11, 1.35) for MI (p-trend<0.0001), and 1.17 (1.05, 1.29) for stroke (p-trend=0.003). Additional adjustment for lifestyle factors, co-morbidities and sleep-related factors modestly attenuated these associations. Higher sleep irregularity was associated with higher CVD risk irrespective of genetic risk (p-interaction=0.43), but this association was stronger among individuals with longer average sleep duration >8 hours (p-interaction=0.006)

Conclusions

Higher night-to-night variation in accelerometer-measured sleep duration was associated with consistently higher risks for major CVD events. The association did not seem to be modified by genetic risk for CVD and was more pronounced in long sleepers.
Comparison of Different Diagnostic Criteria of68Ga-Pentixafor PET/CT for the Classification of Primary Aldosteronism
Authors: Zhang Xiangshuang , He Furong , Song Ying , Jing Ying , Hu Jinbo , Shen Hang , Zhang Aipin , He Wenwen , Feng Zhengping , Li Qifu , Pang Hua , Yang Shumin
Published: July 2024

Background

68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT) is an emerging method for the classifying primary aldosteronism (PA). How to use this method for PA classification is still controversial.

Methods

A retrospective study was conducted in patients with PA who underwent PET/CT. These patients had a classification diagnosis of unilateral PA (UPA) or bilateral PA (BPA) based on adrenal venous sampling or post-surgical outcomes. Area under the receiver operating characteristic curve (AUC), specificity and sensitivity were used to analyze the accuracy of the lateralization index (LI) based on adrenal maximum standardized uptake value (SUVmax), dominant side SUVmaxadjusted by liver, dominant side of SUVmaxand visual analysis.

Results

A total of 208 PA patients were included, with 128 UPA and 80 BPA. The AUC for diagnosing UPA using LI and visual analysis were 0.82 [95% CI, 0·77-0·87] and 0.82 (95% CI, 0·76-0·87), respectively, higher than the dominant side of SUVmax[0.72, (95%CI, 0·65-0·78)] and dominant side SUVmaxadjusted by liver [0.71,(95%CI, 0·64-0·77)]. Visual analysis showed a sensitivity of 0.73 (95%CI,0.65-0.81) and a specificity of 0.88(95%CI,0.80-0.95). The LI cutoff of 1.50 resulted the highest Youden Index of 0.59, with a sensitivity of 0.68 (95%CI,0.59-0.76) and a specificity of 0.91 (95%CI,0.83-0.96). When the LI cutoff was increased to 1.65, the sensitivity reduced to 0.61 (95%CI,0.53-0.70), while the specificity increased to 0.96 (95%CI,0.89-1.00).

Conclusion

Both LI and visual analysis of PET/CT could be used in the classification diagnosis of PA. Nevertheless, visual analysis is more sensitive, and LI is more advantageous in specificity.
Gut microbiota metabolically mediate intestinal helminth infection in Zebrafish
Authors: Hammer Austin J , Gaulke Christopher A , García - Jaramillo Manuel , Leong Connor , Morre Jeff T , Sieler Michael James , Stevens Jan F. , Jiang Yuan , Maier Claudia S. , Kent Michael L , Sharpton Thomas J
Published: July 2024

Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome, and that changes in the gut microbiome are associated with variation in a class of endogenously-produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlights specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.
Urea assimilation and oxidation supports the activity of a phylogenetically diverse microbial community in the dark ocean
Authors: Arandia-Gorostidi Nestor , Jaffe Alexander L. , Parada Alma E. , Kapili Bennett J. , Casciotti Karen L. , Salcedo Rebecca S. R. , Baumas Chloé M. J. , Dekas Anne E.
Published: July 2024

Urea is hypothesized to be an important source of nitrogen and chemical energy to microorganisms in the deep sea; however, direct evidence for urea use below the epipelagic ocean is lacking. Here, we explore urea utilization from 50 to 4000 meters depth in the northeastern Pacific Ocean using metagenomics, nitrification rates, and single-cell stable-isotope-uptake measurements with nanoscale secondary ion mass spectrometry (nanoSIMS). We find that the majority (>60%) of active cells across all samples assimilated urea-derived N, and that cell-specific nitrogen-incorporation rates from urea were higher than that from ammonium. Both urea concentrations and assimilation rates relative to ammonium generally increased below the euphotic zone. We detected ammonia- and urea-based nitrification at all depths at one of two sites analyzed, demonstrating their potential to support chemoautotrophy in the mesopelagic and bathypelagic regions. Using newly generated metagenomes we find that theureC gene, encoding the catalytic subunit of urease, is found within 39% of deep-sea cells in this region, including the Nitrosophaerota (likely for nitrification) as well as thirteen other phyla such as Proteobacteria, Verrucomicrobia, Plantomycetota, Nitrospinota, and Chloroflexota (likely for assimilation). Analysis of public metagenomes revealedureCwithin 10-46% of deep-sea cells around the world, with higher prevalance below the photic zone, suggesting urea is widely available to the deep-sea microbiome globally. Our results demonstrate that urea is a nitrogen source to abundant and diverse microorganisms in the dark ocean, as well as a significant contributor to deep-sea nitrification and therefore fuel for chemoautotrophy.
AutoMorFi: Automated Whole-image Morphometry in Fiji/ImageJ for Diverse Analyses and Discoveries
Authors: Bouadi Ouzéna , Yao Chenkai , Zeng Jason , Beason Danielle , Inda Nyomi , Malone Zoe , Yoshihara Jonathan , Manjally Amritha Vinayak , Johnson Clifton , Cherry Jonathan , Chen Chin-Yi , Huang Tzu-Chieh , Popovic Bogdana , Henley Maria , Liu Guangmei , Aichelman Hannah , Davies Sarah W. , Tian Yuan , Man Hengye , Gilmore Thomas , Ozsen Elif , Harder Kristen , Walentek Peter , Kharitonova Elizabeth K. , Zeldich Ella , Pitt David , Tay Tuan Leng
Published: July 2024

Running on the highly popular and accessible ImageJ/Fiji platform for biological image analysis, we have established AutoMorFi as a streamlined interface for automated whole-image morphometric analysis that generates at least 47 measurements per cell or object in under 1 minute. We performed multiple validated cluster and principal component analyses on nonredundant morphometric parameters derived from AutoMorFi for various cell types, objects, and organisms. We used images of rodent macrophages, human postmortem brain tissues from multiple sclerosis (MS) and Alzheimer’s disease (AD) patients, iPSC/animal models for Down’s syndrome and autism spectrum disorder (ASD), and organisms such as sea anemone and corals. AutoMorFi’s adaptability extends across diverse imaging modalities including brightfield, confocal, or widefield fluorescence microscopy as well as underwater photography. Due to its unlimited and unbiased sampling across any image and high potential for modification and customization, using AutoMorFi has led to the discovery of new distinguishing features in previously studied cell types and organisms as well as the development of rapid diagnostic approaches. AutoMorFi represents a transformative tool that will accelerate morphometric analysis and offer broad relevance in biological studies.
What NLR you recognizing? Predicted binding affinities- and energies may be used to identify novel NLR-effector interactions
Authors: Fick Alicia , Fick Jacobus Lukas Marthinus , Swart Velushka , van den Berg Noëlani
Published: July 2024

Nucleotide binding Leucine-rich repeat (NLR) proteins play a crucial role in effector recognition and activation of Effector triggered immunity in plants following pathogen infection. Advances in genome sequencing have led to the identification of a myriadNLRsin numerous agriculturally important plant species. However, deciphering which NLR proteins recognize specific pathogen effectors remains a challenge. Predicting NLR-effector interactionsin silicowould provide a more targeted approach for experimental validation, critical for elucidating function, and advancing our understanding of NLR-triggered immunity. In this study, NLR-effector protein complex structures were predicted using AlphaFold2-Multimer for all experimentally validated NLR-effector interactions. Binding affinities– and energies were predicted using 97 machine learning models from Area-affinity. We show that predicted structures with an AlphaFold confidence score > 0.42 have acceptable accuracy, and can be used to investigate NLR-effector interactionsin silico. Binding affinities for 58 NLR-effector complexes ranged between –8.5 and –10.6 log(K), and binding energies between –11.8 and –14.4 kcal/mol, depending on the Area-Affinity model used. For 2427 “forced” NLR-effector complexes, these estimates showed larger variability, enabling the identification of novel NLR-effector complexes with 99% accuracy using an Ensemble machine learning model. The narrow range of binding energies– and affinities for true interactions suggest a specific change in Gibbs free energy, and thus conformational change, is required for NLR activation. This is the first study to provide a method for predicting NLR-effector interactions, applicable to all plant-pathogen interactions. Finally, the NLR-Effector Interaction Classification (NEIC) resource can streamline research efforts by identifying NLRs important for providing resistance against plant pathogens, advancing our understanding of plant immunity.
Concatemer Assisted Stoichiometry Analysis (CASA): targeted mass spectrometry for protein quantification
Authors: Cai Jiaxi , Quan Yun , Zhang Cindy Yuxuan , Wang Ziyi , Hinshaw Stephen M. , Zhou Huilin , Suhandynata Raymond T.
Published: July 2024

Large multi-protein machines are central to multiple biological processes. However, stoichiometric determination of protein complex subunits in their native states presents a significant challenge. This study addresses the limitations of current tools in accuracy and precision by introducing concatemer-assisted stoichiometry analysis (CASA). CASA leverages stable isotope-labeled concatemers and liquid chromatography parallel reaction monitoring mass spectrometry (LC-PRM-MS) to achieve robust quantification of proteins with sub-femtomole sensitivity. As a proof-of-concept, CASA was applied to study budding yeast kinetochores. Stoichiometries were determined forex vivoreconstituted kinetochore components, including the canonical H3 nucleosomes, centromeric (Cse4CENP-A) nucleosomes, centromere proximal factors (Cbf1 and CBF3 complex), inner kinetochore proteins (Mif2CENP-C, Ctf19CCANcomplex), and outer kinetochore proteins (KMN network). Absolute quantification by CASA revealed Cse4CENP-Aas a cell-cycle controlled limiting factor for kinetochore assembly. These findings demonstrate that CASA is applicable for stoichiometry analysis of multi-protein assemblies.

This study presents Concatemer-Assisted Stoichiometry Analysis (CASA) to address a common challenge in cell biological research: quantifying the number of each protein subunit in a native protein complex.
Distinct patterns of microbiota and its function in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment and systemic inflammation
Authors: Buttler Laura , Velazquez Ramirez David A. , Tiede Anja , Conradi Anna M. , Woltemade Sabrina , Geffers Robert , Bremer Birgit , Spielmann Vera , Kahlhoefer Julia , Kraft Anke , Schlueter Dirk , Cornberg Markus , Wedemeyer Heiner , Falk Christine S. , Vital Marius , Maasoumy Benjamin
Published: July 2024

Background: Decompensated liver cirrhosis (dLC) is associated with a dysbalanced microbiome, however, reasons for those observations and resulting consequences for patients are largely unexplored. We aimed to characterize bacterial and fungal components of gut microbiota applying quantitative genome-resolved metagenomics and investigate their relation with gut barrier integrity, inflammation and how this impacts the clinical outcome of dLC patients. Methods: Samples were collected prospectively from 95 consecutive hospitalized dLC patients between 2017 and 2022. Metagenomic shot-gun sequencing coupled to flow-cytometric analyses were performed for qualitative and quantitative insights into gut microbiota on a compositional and functional level. Plasma, CRP, Zonulin and CD163 were measured to investigate host functions. Competing risk analyses were performed to compare cirrhosis-related complications within 90 days. Results: Median baseline MELD was 16 and median age 57.6 years. Patients were clustered into three groups (G1-G3) showing greatly distinct microbial patterns. G1 displayed lowest diversity and highest Enterococcus relative abundance (77.97 %), whereas G2 was dominated by Bifidobacteria (52.31 %). G3 was most diverse and clustered most closely with HC. Bacterial concentrations in patients were lower compared with HC (median 2.65 x 109 cells/gram stool), especially for G1 (median of 2.65 x 109 cells/gram stool); G2 and G3 were in-between the two. Fungi were primarily detected in patient samples and an overgrowth in G1 that was dominated by Candida spp (51.63 %) was observed. Moreover, G1-patients most frequently received antibiotics (n=33; 86.8 %) at baseline and had higher plasma levels of Zonulin (p=0.044), CD163 (p=0.019) and a numerically higher incidence of infections (p=0.09). Conclusion: Different bacterial clusters were observed at qualitative and quantitative levels and correlated with fungal abundance. Antibiotic treatment contributed to dysbiosis in patients with dLC, which translated into impairment of the intestinal barrier, translocation and systemic inflammation.
A novel quinone biosynthetic pathway illuminates the evolution of aerobic metabolism
Authors: Elling Felix J , Pierrel Fabien , Chobert Sophie-Carole , Abby Sophie S , Evans Thomas W , Reveillard Arthur , Pelosi Ludovic , Schnoebelen Juliette , Hemingway Jordon D , Boumendjel Ahcene , Becker Kevin W , Blom Pieter , Cordes Julia , Nathan Vinitra , Baymann Frauke , Lucker Sebastian , Spieck Eva , Leadbetter Jared R , Hinrichs Kai-Uwe , Summons Roger E , Pearson Ann
Published: July 2024

The dominant organisms in modern oxic ecosystems rely on respiratory quinones with high redox potential (HPQs) for electron transport in aerobic respiration and photosynthesis. The diversification of quinones, from low redox potential in anaerobes to HPQs in aerobes, is assumed to have followed Earth's surface oxygenation ~2.3 billion years ago. However, the evolutionary origins of HPQs remain unresolved. Here, we characterize the structure and biosynthetic pathway of a novel ancestral HPQ, methyl-plastoquinone, that is unique to bacteria of the phylumNitrospirota. Methyl-plastoquinone is structurally related to the two previously known HPQs, plastoquinone fromCyanobacteriota/chloroplasts and ubiquinone fromPseudomonadota/mitochondria, respectively. We demonstrate a common origin of the three HPQ biosynthetic pathways that predates the emergence ofNitrospirota,Cyanobacteriota, andPseudomonadota. An ancestral HPQ biosynthetic pathway evolved ≥ 3.4 billion years ago in an extinct lineage and was laterally transferred to these three phyla ~2.5-3.2 billion years ago. We show thatCyanobacteriotaandPseudomonadotawere ancestrally aerobic and thus propose that aerobic metabolism using HPQs significantly predates Earth's surface oxygenation. Two of the three HPQ pathways were later obtained by eukaryotes through endosymbiosis forming chloroplasts and mitochondria, enabling their rise to dominance in modern oxic ecosystems.
Histone H2B Monoubiquitylation Regulates Elongation-to-Termination Transition in RNA Polymerase II Transcription
Authors: Bandyopadhyay Tirthankar , Basu Baidehi , Parua Pabitra K.
Published: July 2024

RNA Polymerase II (Pol II)-dependent transcription is meticulously regulated during initiation, elongation, termination, and two pivotal transitions: from initiation to elongation and from elongation to termination1. The successful transition from elongation to termination is vital for accurate transcription termination2,3. While elongation and termination have been extensively studied, the regulatory mechanisms governing the transition between these stages are not fully understood. Here we report that, in fission yeastSchizosaccharomyces pombe(S. pombe) and human cells, Cdk9 and its cyclin partner (Cyclin T in humans, and Pch1 inS. pombe) disengage from the elongation machinery near gene 3’-ends, as Pol II crosses the cleavage and polyadenylation signal (CPS). Concurrently, chromatin immunoprecipitation (ChIP) data shows an increased association of Dis2 (the PP1 ortholog inS. pombe)4beyond the CPS. Additionally, ChIP-seq indicates that histone H2B monoubiquitylation (H2Bub1) is pivotal for Cdk9 occupancy but serves differential roles along the gene. H2Bub1 facilitates Cdk9 chromatin recruitment during elongation but prompts Cdk9 dissociation from the elongation complex as Pol II traverses the CPS. Furthermore, inS. pombe, disruptions of H2Bub1 inhtb1-K119R5and sustained levels inubp8D6inversely affect the chromatin occupancy of Pol II, Pol II CTD phosphorylation within the heptad repeats, Spt5, phosphorylated Spt5 (pSpt5), Dis2, components of the mRNA 3’-end processing complex (Pfs2 and Pla1), and termination factors Rhn1 (Rtt103) and Pcf1 around the CPS— diminishing with H2Bub1 loss and increasing with H2Bub1 stabilization. In essence, our data indicates that the H2Bub1-mediated eviction of Cdk9 as Pol II navigates the CPS precipitates a rise in PP1 binding, which, in turn, dephosphorylates pSpt5, slowing Pol II to facilitate efficient termination. The unique modulation of Cdk9 occupancy by H2Bub1 during transcription progression presents a compelling, novel concept requiring further exploration.
A fluorescent biosensor for the visualization of agmatine
Authors: Kröger Pascal , Stiel Andre C. , Stüven Birthe , Shanmugaratnam Sooruban , Schoch Susanne , Wachten Dagmar , Höcker Birte
Published: July 2024

Agmatine is known to regulate various neurotransmitter systems, yet the underlying molecular mechanisms remain elusive. To visualize agmatine dynamics in cellular networks and thereby unravel its physiological functions, we developed a genetically encoded fluorescent agmatine biosensor (AGMsen) based on the periplasmic putrescine binding protein PotF. We first analyzed the agmatine binding properties of the PotF receptor module based on its crystal structure and introduced mutations into the binding pocket to favor agmatine binding over other biogenic amines. Validation of AGMsen functionality across different cell types, including primary neuronal cultures, demonstrates its ability of real-time agmatine visualization. Thus, the sensor can serve as a valuable tool to advance our understanding of agmatine distribution and dynamics, and shed light on their effect on neuronal functionsin vivo.