bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra- and inter-temporal effort allocation and profit-maximizing strategy of trawl fishery
Authors: Alizadeh Ashrafi Tannaz , Abe Keita
Published: August 2021

Bottom trawlers are engaged in multi-species fisheries and fish for profit. In quota-regulated fisheries, intra- and inter-temporal substitutions of fishing effort is regarded as a key mechanisms that influences the profitability of the fishing portfolio. The feeding and spawning migration patterns of the available fish species in the fishing portfolio alter the bio-economic conditions of the different fishing areas. In addition, the spatial heterogeneity among different fishing areas in terms of the fuel costs and travel distance, accessibility to other fishing fleets, and sea ice extent affects the relative attractiveness of the fishing areas and further complicates the decisions underlying the effort allocation, such as when and where to fish what and how much to fish to maximize the profit. In this regard, the aim of this article is to identify the key drivers of intra- and inter-temporal effort allocation in a multi-species trawl fishery consisting of 61 Norwegian trawl vessels targeting cod, saithe, and haddock, the aim being to maximize the fishing profit within the quota constraints. We adopted a two-step Heckman estimator that incorporates the relative attractiveness of three heavily trawled areas, the southern and northern parts of the west coast of Norway and the high sea areas of the Arctic. The relative attractiveness is specified by the fish availability, measured using the catch per unit of effort, prices of the target species, fuel cost, intensity of the coastal fleet's participation in winter fishery, and seasonal sea ice extent in the Barents Sea during the period 2011–2016. Our results show that region-specific attributes and spatial margins have a profound impact on the intra-temporal and inter-temporal allocation of fishing effort to maximize the seasonal profit. Furthermore, we found evidence of economically rational behaviour of the Norwegian trawlers in constantly reallocating their fishing effort in response to the changes in the relative attractiveness of the selected fishing areas over the course of a fishing year.
“According to the Polls…” Opinion Poll Coverage in Network Evening News during the 2020 U.S. Election Campaign
Authors: Beckers Kathleen
Published: August 2021

After news media and pollsters were unsuccessful in predicting recent political outcomes such as the 2016 U.S. election, opinion polls came under scrutiny. Journalists were accused of not providing audiences the tools to correctly interpret poll information. Using a content analysis of all evening news items from CBS, ABC, and NBC from the final two months before the 2020 U.S. general election, we analyzed the quality of poll coverage. We find that half of the references to election polls are “diffuse,” in which journalists refer to “the polls” in a general manner. When news items do cover specific poll results, media often disclose the absolute minimal essential information (e.g., population and error margin), but fail to provide additional methodological details.
Localized patterns and semi-strong interaction, a unifying framework for reaction–diffusion systems
Authors: Al Saadi Fahad , Champneys Alan , Verschueren Nicolas
Published: August 2021

Systems of activator–inhibitor reaction–diffusion equations posed on an infinite line are studied using a variety of analytical and numerical methods. A canonical form is considered, which contains all known models with simple cubic autocatalytic nonlinearity and arbitrary constant and linear kinetics. Restricting attention to models that have a unique homogeneous equilibrium, this class includes the classical Schnakenberg and Brusselator models, as well as other systems proposed in the literature to model morphogenesis. Such models are known to feature Turing instability, when activator diffuses more slowly than inhibitor, leading to stable spatially periodic patterns. Conversely in the limit of small feed rates, semi-strong interaction asymptotic analysis shows existence of isolated spike-like patterns. This paper describes the broad bifurcation structures that connect these two regimes. A certain universal two-parameter state diagram is revealed in which the Turing bifurcation becomes sub-critical, leading to the onset of homoclinic snaking. This regime then morphs into the spike regime, with the outer-fold being predicted by the semi-strong asymptotics. A rescaling of parameters and field concentrations shows how this state diagram can be studied independently of the diffusion rates. Temporal dynamics is found to strongly depend on the diffusion ratio though. A Hopf bifurcation occurs along the branch of stable spikes, which is subcritical for small diffusion ratio, leading to collapse to the homogeneous state. As the diffusion ratio increases, this bifurcation typically becomes supercritical and interacts with the homoclinic snaking and also with a supercritical homogeneous Hopf bifurcation, leading to complex spatio-temporal dynamics. The details are worked out for a number of different models that fit the theory using a mixture of weakly nonlinear analysis, semi-strong asymptotics and different numerical continuation algorithms.
SOCS: negative regulators of cytokine signaling for immune tolerance
Authors: Yoshimura Akihiko , Ito Minako , Mise-Omata Setsuko , Ando Makoto
Published: August 2021

Cytokines are important intercellular communication tools for immunity. Many cytokines promote gene transcription and proliferation through the JAK/STAT (Janus kinase/signal transducers and activators of transcription) and the Ras/ERK (GDP/GTP-binding rat sarcoma protein/extracellular signal-regulated kinase) pathways, and these signaling pathways are tightly regulated. The SOCS (suppressor of cytokine signaling) family members are representative negative regulators of JAK/STAT-mediated cytokine signaling and regulate the differentiation and function of T cells, thus being involved in immune tolerance. Human genetic analysis has shown that SOCS family members are strongly associated with autoimmune diseases, allergy and tumorigenesis. SOCS family proteins also function as immune-checkpoint molecules that contribute to the unresponsiveness of T cells to cytokines.
Osteoimmunology as an intrinsic part of immunology
Authors: Takayanagi Hiroshi
Published: August 2021

Osteoimmunology has emerged as a field linking immunology and bone biology, but it has yet to be recognized as belonging to mainstream immunology. However, the extent of the research fields immunology actually covers has been enormously widened, and it is now ready to include such an interdisciplinary subject. One of the most obvious examples of an interaction between the immune and bone systems is the pathogenesis of rheumatoid arthritis, where bone resorption is increased by the autoimmune response. Moreover, the regulation of the immune system by bone cells has been clearly demonstrated by the finding that osteoprogenitor cells contribute to hematopoietic stem cell maintenance as well as the suppression of hematopoietic malignancy. Thus, the bidirectional dialogue has been established and inevitably will lead to the union of bone and immunity. Here, I summarize the history and concept of osteoimmunology, providing a perspective on the future of immunology.
Express check-in: developing a personal health record for patients admitted to hospital with medical emergencies: a mixed-method feasibility study
Authors: Subbe Christian P , Tomos Hawys , Jones Gwenlli Mai , Barach Paul
Published: August 2021

Background

Patient participation is increasingly recognized as a key component in the redesign of healthcare processes and is advocated as a means to improve patient safety.

Objective

To explore the usage of participatory engagement in patient-created and co-designed medical records for emergency admission to the hospital.

Methods

design: prospective iterative development and feasibility testing of personal health records; setting: an acute medical unit in a university-affiliated hospital; participants: patients admitted to hospital for medical emergencies; interventions: we used a design-led development of personal health record prototypes and feasibility testing of records completed by patients during the process of emergency admission. ‘Express-check-in’ records contained items of social history, screening questions for sepsis and acute kidney injury in addition to the patients’ ideas, concerns and expectations; main outcome measures: the outcome metrics focused on feasibility and a selection of quality domains, namely effectiveness of recording relevant history, time efficiency of the documentation process, patient-centredness of resulting records and staff and patient feedback. The incidence of sepsis and acute kidney injury were used as surrogate measures for assessing the safety impact.

Results

The medical record prototypes were developed in an iterative fashion and tested with 100 patients, in which 39 patients were 70 or older and 25 patients were classified as clinically frail. Ninety-six per cent of the data items were completed by patients with no or minimal help from healthcare professionals. The completeness of these patient records was superior to that of the corresponding medical records in that they contained deeply held beliefs and fears, whereas concerns and expectations recorded by patients were only mirrored in a small proportion of the formal clinical records. The sepsis self-screening tool identified 68% of patients requiring treatment with antibiotics. The intervention was feasible, independent of the level of formal education and effective in frail and elderly patients with support from family and staff. The prototyped records were well received and felt to be practical by patients and staff. The staff indicated that reading the patients’ documentation led to significant changes in their clinical management.

Conclusions

Medical record accessibility to patients during hospital care contributes to the co-management of personal healthcare and might add critical information over and above the records compiled by healthcare professionals.
Novel tigecycline resistance gene cluster tnfxB3-tmexCD3-toprJ1b in Proteus spp. and Pseudomonas aeruginosa, co-existing with tet(X6) on an SXT/R391 integrative and conjugative element
Authors: Wang Cheng-Zhen , Gao Xun , Lv Lu-Chao , Cai Zhong-Peng , Yang Jun , Liu Jian-Hua
Published: August 2021

Objectives

To characterize a novel MDR efflux pump gene cluster tnfxB3-tmexCD3-toprJ1b carried by Proteus spp. and Pseudomonas aeruginosa strains from chickens.

Methods

Antimicrobial susceptibility testing, conjugation and WGS were performed to characterize tnfxB3-tmexCD3-toprJ1b-positive isolates. Cloning and reverse transcription-quantitative PCR were performed to investigate the function of tnfxB3-tmexCD3-toprJ1b.

Results

The WGS data revealed that a novel efflux pump gene cluster, tnfxB3-tmexCD3-toprJ1b, was identified on the chromosome of the Proteus cibarius strain SDQ8C180-2T, where an SXT/R391-family integrative and conjugative element (ICE) was found to co-carry tet(X6) and tnfxB3-tmexCD3-toprJ1b. Further retrospective analysis found two other tnfxB3-tmexCD3-toprJ1b variants in a Proteus mirabilis isolate and a P. aeruginosa isolate, respectively. tmexCD3-toprJ1b and its variants increased the MICs of tigecycline (8-fold) and other antibiotics (2–8-fold) in Escherichia coli host strains. The TNfxB3 protein down-regulated the expression of the tmexCD3-toprJ1b operon. Moreover, genetic-context analyses showed that tnfxB3-tmexCD3-toprJ1b together with adjacent integrase genes appeared to compose a transferable module ‘int1-like+int2-like+hp1+hp2+ISCfr1+tnfxB3-tmexCD3-toprJ1b’, which was inserted into the umuC-like gene of this ICE. Further analysis of the tnfxB3-tmexCD3-toprJ1b-harbouring sequences deposited in GenBank revealed similar transferable modules inserted into umuC-like genes in plasmids or chromosomes of Klebsiella pneumoniae, Pseudomonas spp. and Aeromonas spp., implying that these modules could be transferred across different bacterial species.

Conclusions

To the best of our knowledge, this is the first identification of a novel tigecycline gene cluster, tmexCD3-toprJ1b, which co-exists with tet(X6) within an ICE. More attention should be paid to the co-transfer of these two tigecycline resistance determinants via an ICE to other Gram-negative bacteria.
Retrospective Evaluation of the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) Score
Authors: Poore Brad , Hamilton Robert , Kelliher Michael T , Mahmood Sundis , Mindiola-Romero Andres E , Richards Ryland , Motanagh Samaneh , Cervinski Mark A , Nerenz Robert D
Published: August 2021

Background

Autoimmune encephalitis (AE) is a rare collection of disorders that present with a diverse and often nebulous set of clinical symptoms. Indiscriminate use of multi-antibody panels decreases their overall utility and predictive value. Application of a standardized scoring system may help reduce the number of specimens that generate misleading or uninformative results.

Methods

The results of autoimmune encephalopathy, epilepsy, or dementia autoantibody panels performed on serum (n = 251) or cerebrospinal fluid (CSF) (n = 235) specimens from October 9th, 2016 to October 11th, 2019 were collected. Retrospective chart review was performed to calculate the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score for patients with an antibody above the assay-specific reference interval and to classify results as true or false positive.

Results

Of the 486 specimens, 60 (12.3%) generated positive results for any AE antibody (6 CSF and 54 serum). After removing 2 duplicate specimens collected from a single patient, 10 of the remaining 58 were determined to be true positives and 8 contained neural-specific antibodies. Application of the APE2 score revealed that 89% of all true positives and 86% of specimens with neural-specific antibodies had a score ≥4. In contrast, 76% of false positives, 74% of clinically nonspecific antibodies, and 85% of the negative specimens had an APE2 score <4.

Conclusion

The APE2 score can improve the diagnostic utility of autoimmune encephalopathy evaluation panels.
Achievement of the minimal clinically important difference following open proximal hamstring repair
Authors: Lawton Cort D , Sullivan Spencer W , Hancock Kyle J , Burger Joost A , Nawabi Danyal H , Kelly Bryan T , Ranawat Anil S , Nwachukwu Benedict U
Published: August 2021

There is a paucity of literature on patient-reported outcome measures (PROMs) following proximal hamstring repair beyond return to play, patient satisfaction and pain improvement. The minimal clinically important difference (MCID) defines the minimum degree of quantifiable improvement that a patient can perceive, but the MCID and predictors of this measure have not been defined for this patient population. This study aimed to define the MCID and determine the efficacy of open proximal hamstring repair through achievement of MCID and identify characteristics predictive of achieving MCID. A retrospective cohort review of an institutional hip registry was conducted, analyzing the modified Harris Hip Score (mHHS) and International Hip Outcome Tool (iHOT-33). MCID was calculated using a distribution-based method. Demographic and clinical variables predictive of achieving MCID were analyzed using univariable and multivariate logistic regression analyses. Thirty-nine patients who underwent open proximal hamstring repair were included. The mean patient age was 48.5 ± 12.4 years, with a mean follow-up of 37.1 ± 28 months. The MCID was determined for each PROM (mHHS—11.8; iHOT-33—12.6). A high percentage of patients achieved MCID for both PROMs (mHHS—85.7%; iHOT-33—91.4%). Univariate logistical regression demonstrated increased age (P = 0.163), increased body mass index (BMI; P = 0.072), requirement for inpatient admission (P = 0.088) and pre-operative iHOT-33 (P = 0.104) trended towards clinically significant predictors of not achieving MCID. A high percentage of patients achieved MCID while age, BMI, inpatient admission and pre-operative iHOT-33 appear to influence the achievement of clinically significant outcome in patients undergoing open proximal hamstring repair.
Spatio-temporal modelling of the effect of selected environmental and land-use factors on acid grassland vegetation
Authors: Damgaard Christian
Published: August 2021

Acid grasslands are threatened both by agricultural intensification with nutrient addition and increased livestock densities as well as by land abandonment. In order to understand and quantify the effect of selected environmental and land-use factors on the observed variation and changes in the vegetation of acid grasslands, large-scale spatial and temporal pin-point plant cover monitoring data are fitted in a structural equation model. The important sources of measurement and sampling uncertainties have been included using a hierarchical model structure. Furthermore, uncertainties associated with the measurement and sampling are separated from the process uncertainty, which is important when generating ecological predictions that may feed into local conservation management decisions. Generally, increasing atmospheric nitrogen deposition led to more grass-dominated acid grassland habitats at the expense of the cover of forbs. Sandy soils were relatively more acidic, and the effects of soil type on the vegetation include both direct effects of soil type and indirect effects mediated by the effect of soil type on soil pH. Both soil type and soil pH affected the vegetation of acid grasslands. Even though only a relatively small proportion of the temporal variation in cover was explained by the model, it would still be useful to quantify the uncertainties when using the model for generating local ecological predictions and adaptive management plans.
UAVs as remote sensing platforms in plant ecology: review of applications and challenges
Authors: Sun Zhongyu , Wang Xiaonian , Wang Zhihui , Yang Long , Xie Yichun , Huang Yuhui
Published: August 2021

Aims

Unmanned aerial vehicles (UAVs), i.e. drones, have recently emerged as cost-effective and flexible tools for acquiring remote sensing data with fine spatial and temporal resolution. It provides a new method and opportunity for plant ecologists to study issues from individual to regional scales. However, as a new method, UAVs remote sensing applications in plant ecology are still challenged. The needs of plant ecology research and the application development of UAVs remote sensing should be better integrated.

Methods

This report provides a comprehensive review of UAV-based remote sensing applications in plant ecology to synthesize prospects of applying drones to advance plant ecology research.

Important Findings

Of the 400 references, 59% were published in remote sensing journals rather than in plant ecology journals, reflecting a substantial gap between the interests of remote sensing experts and plant ecologists. Most of the studies focused on UAV remote sensing’s technical aspects, such as data processing and remote sensing inversion, with little attention on answering ecological questions. There were 61% of studies involved community-scale research. RGB and multispectral cameras were the most used sensors (75%). More ecologically meaningful parameters can be extracted from UAV data to better understand the canopy surface irregularity and community heterogeneity, identify geometrical characteristics of canopy gaps and construct canopy chemical assemblies from living vegetation volumes. More cooperation between plant ecologists and remote sensing experts is needed to promote UAV remote sensing in advancing plant ecology research.
COVID-19 Vaccine Distribution: Bolstering the Air Force Immunizations Model
Authors: Adams Karla E , Smith Derek , White Kevin
Published: August 2021

From its emergence and declaration as a worldwide pandemic, coronavirus disease-2019 (COVID-19) has been associated with significant medical and logistical challenges. Initial obstacles ranged from the need to develop testing platforms to the determination of effective treatments to decrease the significant morbidity and mortality associated with the disease. Due to significant scientific breakthroughs, the most recent pressing challenge has been the distribution of vaccines against severe acute respiratory syndrome coronavirus 2 to prevent the spread of the infection across the world. Historically, the U.S. Military has been involved in immunizations delivery to prevent disease among its troops. This experience has led to the establishment of programs designed to distribute safe vaccinations to service members and beneficiaries. It is upon this infrastructure that the Air Force (AF) medical community was thrust to devise and execute COVID-19 vaccine delivery implementation across all military treatment facilities. In the AF, specialty trained allergist and immunologists provide the technical expertise for the establishment and execution of the AF immunizations program. These medical professionals have the proficiency, knowledge, and experience to run efficient mass immunization events in order to provide vaccines in a safe and rapid environment. Despite this, significant challenges attributable to the variable and novel nature of COVID-19 vaccine logistical requirements have led to unanswered questions and debate that needed resolution before and during the launch of this program. Here we describe the process for establishing a mass vaccination program for COVID-19 vaccine delivery and our experience-based problem solving approach at a large AF military treatment facility.
Eumops floridanus (Chiroptera: Molossidae)
Authors: Vannatta Jessica M , Gore Jeffery A , Mathis Verity L , Carver Brian D
Published: August 2021

Eumops floridanus (Allen, 1932) is a molossid commonly called the Florida bonneted bat or the Florida mastiff bat. Eumops floridanus is the largest species of bat in Florida and is one of 16 species in the genus Eumops. With one of the smallest distributions of any bat in the United States, it is endemic to southern peninsular Florida where it roosts in cavities of live and dead trees and man-made structures. Eumops floridanus was formerly classified as a subspecies of E. glaucinus but has been elevated to species level based on morphology. Due primarily to its restricted distribution, small population size, and the continued loss of habitat, E. floridanus is federally listed as “Endangered” (EN) by the United States Fish and Wildlife Service.
Evidence in disease and non-disease contexts that nonsense mutations cause altered splicing via motif disruption
Authors: Abrahams Liam , Savisaar Rosina , Mordstein Christine , Young Bethan , Kudla Grzegorz , Hurst Laurence D
Published: August 2021

Transcripts containing premature termination codons (PTCs) can be subject to nonsense-associated alternative splicing (NAS). Two models have been evoked to explain this, scanning and splice motif disruption. The latter postulates that exonic cis motifs, such as exonic splice enhancers (ESEs), are disrupted by nonsense mutations. We employ genome-wide transcriptomic and k-mer enrichment methods to scrutinize this model. First, we show that ESEs are prone to disruptive nonsense mutations owing to their purine richness and paucity of TGA, TAA and TAG. The motif model correctly predicts that NAS rates should be low (we estimate 5–30%) and approximately in line with estimates for the rate at which random point mutations disrupt splicing (8–20%). Further, we find that, as expected, NAS-associated PTCs are predictable from nucleotide-based machine learning approaches to predict splice disruption and, at least for pathogenic variants, are enriched in ESEs. Finally, we find that both in and out of frame mutations to TAA, TGA or TAG are associated with exon skipping. While a higher relative frequency of such skip-inducing mutations in-frame than out of frame lends some credence to the scanning model, these results reinforce the importance of considering splice motif modulation to understand the etiology of PTC-associated disease.
Unveiling mRNP composition by fluorescence correlation and cross-correlation spectroscopy using cell lysates
Authors: Mateu-Regué Àngels , Christiansen Jan , Bagger Frederik Otzen , Hellriegel Christian , Nielsen Finn Cilius
Published: August 2021

Understanding the mRNA life cycle requires information about the dynamics and macromolecular composition and stoichiometry of mRNPs. Fluorescence correlation and cross-correlation spectroscopy (FCS and FCCS) are appealing technologies to study these macromolecular structures because they have single molecule sensitivity and readily provide information about their molecular composition and dynamics. Here, we demonstrate how FCS can be exploited to study cytoplasmic mRNPs with high accuracy and reproducibility in cell lysates. Cellular lysates not only recapitulate data from live cells but provide improved readings and allow investigation of single mRNP analysis under particular conditions or following enzymatic treatments. Moreover, FCCS employing minute amounts of cells closely corroborated previously reported RNA dependent interactions and provided estimates of the relative overlap between factors in the mRNPs, thus depicting their heterogeneity. The described lysate-based FCS and FCCS analysis may not only complement current biochemical approaches but also provide novel opportunities for the quantitative analysis of the molecular composition and dynamics of single mRNPs.
NgAgo possesses guided DNA nicking activity
Authors: Lee Kok Zhi , Mechikoff Michael A , Kikla Archana , Liu Arren , Pandolfi Paula , Fitzgerald Kevin , Gimble Frederick S , Solomon Kevin V
Published: August 2021

Prokaryotic Argonautes (pAgos) have been proposed as more flexible tools for gene-editing as they do not require sequence motifs adjacent to their targets for function, unlike popular CRISPR/Cas systems. One promising pAgo candidate, from the halophilic archaeon Natronobacterium gregoryi (NgAgo), has been the subject of debate regarding its potential in eukaryotic systems. Here, we revisit this enzyme and characterize its function in prokaryotes. NgAgo expresses poorly in non-halophilic hosts with most of the protein being insoluble and inactive even after refolding. However, we report that the soluble fraction does indeed act as a nicking DNA endonuclease. NgAgo shares canonical domains with other catalytically active pAgos but also contains a previously unrecognized single-stranded DNA binding domain (repA). Both repA and the canonical PIWI domains participate in DNA cleavage activities of NgAgo. NgAgo can be programmed with guides to nick targeted DNA in Escherichia coli and in vitro 1 nt outside the 3′ end of the guide sequence. We also found that these endonuclease activities are essential for enhanced NgAgo-guided homologous recombination, or gene-editing, in E. coli. Collectively, our results demonstrate the potential of NgAgo for gene-editing and provide new insight into seemingly contradictory reports.
Ephyrae and metaephyrae of Pelagia noctiluca: stage determination, morphometry and shrinkage
Authors: Ottmann Daniel , Leyva Laura , Reglero Patricia , Prieto Laura , Alvarez Itziar
Published: August 2021

Understanding processes occurring in the different life stages of jellyfish is key to advance knowledge on their trophic interactions and population dynamics. We describe four developmental stages of Pelagia noctiluca ephyrae and metaephyrae based on the progress of feeding structures and morphometric measurements on the central disc diameter and total body diameter. Size differs significantly among stages, but it can overlap substantially, suggesting that it is not always coupled with development progress due to different somatic growth. Morphological distinction of stages is biologically important because it implies different levels of food specialization and capture efficiency. We further report a 25% (±13 SD) shrinkage of ephyrae and metaephyrae after storage in 4% formaldehyde solution. This metric can be used in ecological studies focusing on size-related traits of field observed individuals.
Multiparameter in vivo imaging in plants using genetically encoded fluorescent indicator multiplexing
Authors: Waadt Rainer , Kudla Jörg , Kollist Hannes
Published: August 2021

Biological processes are highly dynamic, and during plant growth, development, and environmental interactions, they occur and influence each other on diverse spatiotemporal scales. Understanding plant physiology on an organismic scale requires analyzing biological processes from various perspectives, down to the cellular and molecular levels. Ideally, such analyses should be conducted on intact and living plant tissues. Fluorescent protein (FP)-based in vivo biosensing using genetically encoded fluorescent indicators (GEFIs) is a state-of-the-art methodology for directly monitoring cellular ion, redox, sugar, hormone, ATP and phosphatidic acid dynamics, and protein kinase activities in plants. The steadily growing number of diverse but technically compatible genetically encoded biosensors, the development of dual-reporting indicators, and recent achievements in plate-reader-based analyses now allow for GEFI multiplexing: the simultaneous recording of multiple GEFIs in a single experiment. This in turn enables in vivo multiparameter analyses: the simultaneous recording of various biological processes in living organisms. Here, we provide an update on currently established direct FP-based biosensors in plants, discuss their functional principles, and highlight important biological findings accomplished by employing various approaches of GEFI-based multiplexing. We also discuss challenges and provide advice for FP-based biosensor analyses in plants.
Cerebello-Thalamo-Cortical Hyperconnectivity Classifies Patients and Predicts Long-Term Treatment Outcome in First-Episode Schizophrenia
Authors: Cao Hengyi , Wei Xia , Hu Na , Zhang Wenjing , Xiao Yuan , Zeng Jiaxin , Sweeney John A , Lencer Rebekka , Lui Su , Gong Qiyong
Published: August 2021

It has previously been shown that cerebello-thalamo-cortical (CTC) hyperconnectivity is likely a state-independent neural signature for psychosis. However, the potential clinical utility of this change has not yet been evaluated. Here, using fMRI and clinical data acquired from 214 untreated first-episode patients with schizophrenia (62 of whom were clinically followed-up at least once at the 12th and 24th months after treatment initiation) and 179 healthy controls, we investigated whether CTC hyperconnectivity would serve as an individualized biomarker for diagnostic classification and prediction of long-term treatment outcome. Cross-validated LASSO regression was conducted to estimate the accuracy of baseline CTC connectivity for patient-control classification, with the generalizability of classification performance tested in an independent sample including 42 untreated first-episode patients and 65 controls. Associations between baseline CTC connectivity and clinical outcomes were evaluated using linear mixed model and leave-one-out cross validation. We found significantly increased baseline CTC connectivity in patients (P = .01), which remained stable after treatment. Measures of CTC connectivity discriminated patients from controls with moderate classification accuracy (AUC = 0.68, P < .001), and the classification model had good generalizability in the independent sample (AUC = 0.70, P < .001). Higher CTC connectivity at baseline significantly predicted poorer long-term symptom reduction in negative symptoms (R = 0.31, P = .01) but not positive or general symptoms. These findings provide initial evidence for the putative “CTC hyperconnectivity” anomaly as an individualized diagnostic and prognostic biomarker for schizophrenia, and highlight the potential of this measure in precision psychiatry.
Alterations in Sucrose and Phenylpropanoid Metabolism Affected by BABA-Primed Defense in Postharvest Grapes and the Associated Transcriptional Mechanism
Authors: Li Chunhong , Wang Kaituo , Lei Changyi , Cao Shifeng , Huang Yixiao , Ji Nana , Xu Feng , Zheng Yonghua
Published: August 2021

Defense elicitors can induce fruit disease resistance to control postharvest decay but may incur quality impairment. Our present work aimed to investigate the resistance against Botrytis cinerea induced by the elicitor β-aminobutyric acid (BABA) and to elucidate the specific transcriptional mechanism implicated in defense-related metabolic regulations. The functional dissection results demonstrated that, after inoculation with the fungal necrotroph B. cinerea, a suite of critical genes encoding enzymes related to the sucrose metabolism and phenylpropanoid pathway in priming defense in grapes were transcriptionally induced by treatment with 10 mM BABA. In contrast, more UDP-glucose, a shared precursor of phenylpropanoid and sucrose metabolism, may be redirected to the phenylpropanoid pathway for the synthesis of phytoalexins, including trans-resveratrol and ɛ-viniferin, in 100 mM BABA–treated grapes, resulting in direct resistance but compromised soluble sugar contents. An R2R3-type MYB protein from Vitis vinifera, VvMYB44, was isolated and characterized. VvMYB44 expression was significantly induced upon the grapes expressed defensive reaction. Subcellular localization, yeast two-hybrid, and coimmunoprecipitation assays revealed that the nuclear-localized VvMYB44 physically interacted with the salicylic acid–responsive transcription coactivator NPR1 in vivo for defense expression. In addition, VvMYB44 directly bound to the promoter regions of sucrose and phenylpropanoid metabolism-related genes and transactivated their expression, thus tipping the balance of antifungal compound accumulation and soluble sugar maintenance. Hence, these results suggest that 2R-type VvMYB44 might be a potential positive participant in BABA-induced priming defense in grape berries that contributes to avoiding the excessive consumption of soluble sugars during the postharvest storage.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Circadian rhythm disruption with high‐fat diet impairs glycemic control and bone quality
Authors: LLabre Joan E. , Trujillo Ruben , Sroga Grażyna E. , Figueiro Mariana G. , Vashishth Deepak
Published: August 2021

Biological functions, including glycemic control and bone metabolism, are highly influenced by the body's internal clock. Circadian rhythms are biological rhythms that run with a period close to 24 hours and receive input from environmental stimuli, such as the light/dark cycle. We investigated the effects of circadian rhythm disruption (CRD), through alteration of the light/dark schedule, on glycemic control and bone quality of mice. Ten‐week‐old male mice (C57/BL6, n = 48) were given a low‐fat diet (LFD) or a high‐fat diet (HFD) and kept on a dayshift or altered schedule (RSS3) for 22 weeks. Mice were divided into four experimental groups (n = 12/group): Dayshift/LFD, Dayshift/HFD, RSS3/LFD, and RSS3/HFD. CRD in growing mice fed a HFD resulted in a diabetic state, with a 36.2% increase in fasting glucose levels compared to the Dayshift/LFD group. Micro‐CT scans of femora revealed a reduction in inner and outer surface expansion for mice on a HFD and altered light schedule. Cancellous bone demonstrated deterioration of bone quality as trabecular number and thickness decreased while trabecular separation increased. While HFD increased cortical bone mineral density, its combination with CRD reduced this phenomenon. The growth of mineral crystals, determined by small angle X‐ray scattering, showed HFD led to smaller crystals. Considering modifications of the organic matrix, regardless of diet, CRD exacerbated the accumulation of fluorescent advanced glycation end‐products (fAGEs) in collagen. Strength testing of tibiae showed that CRD mitigated the higher strength in the HFD group and increased brittleness indicated by lower post‐yield deflection and work‐to‐fracture. Consistent with accumulation of fAGEs, various measures of toughness were lowered with CRD, but combination of CRD with HFD protected against this decrease. Differences between strength and toughness results represent different contributions of structural and material properties of bone to energy dissipation. Collectively, these results demonstrate that combination of CRD with HFD impairs glycemic control and have complex effects on bone quality.
8‐acetoxy‐trisulfopyrene as the first activatable fluorogenic probe for add‐and‐read assessment of Organic anion‐transporting polypeptides, OATP1B1, OATP1B3, and OATP2B1
Authors: Ungvári Orsolya , Király Laura , Bakos Éva , Özvegy‐Laczka Csilla
Published: August 2021

Organic anion‐transporting polypeptides, OATP1B1, OATP1B3, and OATP2B1 are multispecific membrane proteins mediating the hepatocellular uptake of structurally diverse endo‐ and exogenous compounds, including various kinds of drugs. Co‐administration of OATP1B/2B1 substrates may lead to altered pharmacokinetics or even toxicity. Therefore, the study of the interaction with these OATPs is essential in drug development and is recommended by international regulatory agencies, the FDA, EMA, and PMDA. In general, radiolabeled indicators are used to measure drug interactions of OATPs, and, lately, fluorescent probes are also gaining wider application in OATP tests. However, all of the currently available methods (either radioactive or fluorescence‐based) comprise multiple steps, including the removal of the indicator in the end of the experiment. Hence, they are not ideally suited for high‐throughput screening. In the current study, in order to find an indicator allowing real‐time assessment of hepatic OATP function, we searched for an activatable fluorogenic OATP substrate. Here, we show that 8‐acetoxypyrene‐1,3,6‐trisulfonate (Ace), a fluorogenic derivative of the hepatic OATP substrate pyranine (8‐hydroxypyrene‐1,3,6‐trisulfonate) enters the cells via OATP1B1/3 or OATP2B1 function. In living cells, Ace is then converted into highly fluorescent pyranine, allowing “no‐wash” measurement of OATP function and drug interactions. Furthermore, we demonstrate that Ace can be used in an indirect assay termed as competitive counterflow suitable to distinguish between transported substrates and inhibitors of OATP1B1. The fluorescence‐based methods described here are unique and open the way toward high‐throughput screening of interactions between new molecular entities and OATPs.
A mutation in desmin makes skeletal muscle less vulnerable to acute muscle damage after eccentric loading in rats
Authors: Langer Henning T. , Mossakowski Agata A. , Avey Alec M. , Wohlgemuth Ross P. , Smith Lucas R. , Zbinden‐Foncea Herman , Baar Keith
Published: August 2021

Desminopathy is the most common intermediate filament disease in humans. The most frequent mutation causing desminopathy in patients is a R350P DES missense mutation. We have developed a rat model with an analogous mutation in R349P Des. To investigate the role of R349P Des in mechanical loading, we stimulated the sciatic nerve of wild‐type littermates (WT) (n = 6) and animals carrying the mutation (MUT) (n = 6) causing a lengthening contraction of the dorsi flexor muscles. MUT animals showed signs of ongoing regeneration at baseline as indicated by a higher number of central nuclei (genotype: P < .0001). While stimulation did not impact central nuclei, we found an increased number of IgG positive fibers (membrane damage indicator) after eccentric contractions with both genotypes (stimulation: P < .01). Interestingly, WT animals displayed a more pronounced increase in IgG positive fibers with stimulation compared to MUT (interaction: P < .05). In addition to altered histology, molecular signaling on the protein level differed between WT and MUT. The membrane repair protein dysferlin decreased with eccentric loading in WT but increased in MUT (interaction: P < .05). The autophagic substrate p62 was increased in both genotypes with loading (stimulation: P < .05) but tended to be more elevated in WT (interaction: P = .05). Caspase 3 levels, a central regulator of apoptotic cell death, was increased with stimulation in both genotypes (stimulation: P < .01) but more so in WT animals (interaction: P < .0001). Overall, our data indicate that R349P Des rats have a lower susceptibility to structural muscle damage of the cytoskeleton and sarcolemma with acute eccentric loading.
Results of Early Proximal Femoral Osteotomy at Skeletal Maturity in Legg-Calvé-Perthes Disease: Implication for the Bypass of Fragmentation Stage
Authors: Kim Sungmin , Oh Ho-Seok , Lim Jun-Hyuk , Cho Seunghyeon , Jung Sung Taek
Published: August 2021

Background:

The aim was to assess the long-term radiographic outcomes of patients with Legg-Calvé-Perthes disease following an early proximal femoral osteotomy (PFO) performed in avascular necrosis stage or early fragmentation stage.

Methods:

In this retrospective study, we analyzed data of 65 patients aged above 6 years at the time of diagnosis with unilateral Legg-Calvé-Perthes disease, following early PFO performed at our institution between 1979 and 2013. We observed the presence of bypassing fragmentation stage, which was classified into complete and incomplete. We compared radiographic outcomes between patients with bypass of fragmentation stage (26 hips) and those without (31 hips). Regarding skeletal maturity, the hips were graded according to the femoral head shapes: spherical, ovoid, or flat.

Results:

The mean age at diagnosis was 7.9 years (range: 6.0 to 11.9 y). The average follow-up period was 11.8 years (range: 5.9 to 22.9 y). Fragmentation bypass occurred in 40.5% (26/65) of patients, with 8 (12.3%) “undetermined” cases. Patients who completely or partially bypassed fragmentation experienced significantly less severe lateral pillar collapse (P=0.016). The femoral head was also significantly more spherical in patients with bypass (P=0.024).

Conclusions:

Our results show that 40.5% of patients who underwent early PFO bypassed the fragmentation stage. The degree of lateral pillar collapse was lower in patients with bypass. In addition, there were significantly more patients with more spherical femoral head in the bypass group.

Level of Evidence:

Level IV—case series.
When Is a Growth-friendly Strategy Warranted? A Matched Comparison of Growing Rods Versus Primary Posterior Spinal Fusion in Juveniles With Early-onset Scoliosis
Authors: Keil Lukas G. , Nash Alysa B. , Stürmer Til , Golightly Yvonne M. , Lin Feng-Chang , Stone Joseph D. , Sanders James O. , Louer Craig R.
Published: August 2021

Background:

In 7 to 11-year-old juveniles with severe early-onset scoliosis (EOS) the optimal surgical option remains uncertain. This study compares growing rods (GRs) followed by definitive posterior spinal fusion (PSF) versus primary PSF in this population. We hypothesized that the thoracic height afforded by GRs would be offset by increased rigidity, more complications, and more operations.

Methods:

This retrospective comparative study included EOS patients aged 7.0 to 11.9 years at index surgery treated with GR→PSF or primary PSF during 2013 to 2020. Primary outcomes were thoracic height gain (ΔT1-12H), major curve, complications, and total operations. Primary PSFs were matched with replacement 1-to-n to GR→PSFs by age at index, etiology, and major curve.

Results:

Twenty-eight GR→PSFs met criteria: 19 magnetically controlled GRs and 9 traditional GRs. Three magnetically controlled GRs were definitively explanted without PSF due to complications. The remaining 25 GR→PSFs were matched to 17 primary PSFs with 100% etiology match, mean Δ major curve 1 degree, and mean Δ age at index 0.5 years (PSFs older). Median ΔT1-12H pre-GR to post-PSF was 4.7 cm with median deformity correction of 37%. Median ΔT1-12H among primary PSFs was 1.9 cm with median deformity correction of 62%. GR→PSFs had mean 1.8 complications and 3.4 operations. Primary PSFs had mean 0.5 complications and 1.3 operations. Matched analysis showed adjusted mean differences of 2.3 cm greater ΔT1-12H among GR→PSFs than their matched primary PSFs, with 25% less overall coronal deformity correction, 1.2 additional complications, and 2.2 additional operations per patient.

Conclusions:

In juveniles aged 7 to 11 with EOS, on average GRs afford 2 cm of thoracic height over primary PSF at the cost of poorer deformity correction and additional complications and operations. Primary PSF affords an average of 2 cm of thoracic height gain; if an additional 2 cm will be impactful then GRs should be considered. However, in most juveniles the height gained may not warrant the iatrogenic stiffness, complications, and additional operations. Surgeons and families should weigh these benefits and harms when choosing a treatment plan.

Level of Evidence:

Level III—retrospective comparative study.
Entire-spine Magnetic Resonance Imaging Findings and Costs in Children With Presumed Adolescent Idiopathic Scoliosis
Authors: Johnson Mitchell A. , Gohel Shivani , Mitchell Stuart L. , Flynn John (Jack) M. , Baldwin Keith D.
Published: August 2021

Background:

Patients with adolescent idiopathic scoliosis (AIS) are commonly monitored for curve progression with spinal radiographs; however, the utility of magnetic resonance imaging (MRI) screening is unclear. The purpose of this study was to assess the findings of screening MRI for patients with a nonsurgical curve size ordered during routine clinical care and compare them with MRI ordered for patients with large curves as part of preoperative screening.

Methods:

All consecutive patients with presumed AIS who underwent entire-spine MRI with a presumed diagnosis of idiopathic scoliosis at a single institution between 2017 and 2019 were retrospectively reviewed. Patients were stratified based on MRI indication into the following groups: preoperative evaluation, pain, neurological symptoms, abnormal radiographic curve appearance, rapidly progressive curve, and other. Neural axis abnormalities recorded included concern for tethered spinal cord, syringomyelia, and Chiari malformation. The MRI findings of preoperative patients with large curves were compared with all other patients. The number needed to diagnose (NND) a neurological finding was calculated in patients whose MRIs were ordered during routine clinical care. The amount charged for each patient undergoing entire-spine MRI was determined by review of our institution’s Financial Decision Support system.

Results:

There were 344 patients included in this study with 214 (62%) MRIs performed for preoperative evaluation. Although MRI abnormalities were found in 49% of patients, only 7.0% (24/344) demonstrated neural axis abnormalities with no difference between preoperative and other indications (P=0.37). For patients with nonsurgical curves undergoing MRI due to a complaint of back pain (n=28), there were no neural axis abnormalities, and a lower rate of disk herniation/degenerative changes detected compared with preoperative MRI (3.6% vs. 18%, P=0.06). Among the 15 patients undergoing MRI for a neurological concern, 1 had a neural axis abnormality that required surgical detethering. The NND for MRI to detect a neural axis abnormality that potentially required neurosurgical intervention in nonpreoperative patients with a neurological concern was 34.4. The average cost for MRI was $17,816 (range: $2601 to $22,411) with a total cost of $2,368,439 for nonsurgical curves.

Conclusions:

Entire-spine MRI for nonpreoperative indications including pain, abnormal radiographic curve appearance, and rapid curve progression has minimal utility for patients with AIS. For patients with neurological complaints, the NND a potentially treatment-altering finding with MRI is 34.4.

Level of Evidence:

Level II—diagnostic.