bluuebunny/crossref_metadata_2025 huggingface dataset:
Strongest Correlation Between Contrast Sensitivity and Morphological Characteristics in Bilateral nAMD
Authors: Hoffmann Laura , Rossouw Petra , Guichard Maria-Magdalena , Hatz Katja
Published: January 2021

In patients with neovascular age-related macular degeneration (nAMD) there is often an inconsistency between their subjective visual impairment and a still relatively preserved standard Early Treatment of Diabetic Retinopathy Study (ETDRS) best corrected visual acuity. Therefore, in order to better capture the specific functional defects in nAMD, other tests need to be evaluated. In a previous study, we reported contrast sensitivity of the better eye to best correlate with near distance and distance vision related quality of life in patients with bilateral nAMD. Here, we evaluated Pelli-Robson contrast sensitivity, ETDRS visual acuity, low luminance visual acuity and Radner maximum reading speed and correlated them with several morphologic parameters as measured on fundus autofluorescence imaging, optical coherence tomography and optical tomography angiography in 54 patients. A multiple regression analysis was performed which correlated each visual function parameter with the anatomic features. The results showed the strongest correlations between the total area of macular geographic atrophy as well as the percentage of geographic atrophy in the central 1 mm and contrast sensitivity. Further, the regression model selected the total area of macular geographic atrophy, the photoreceptor inner and outer segments interface disruption score, the presence of subretinal fibrosis in the central 1 mm and the central retinal thickness as the variables that explained 71% of the variation in contrast sensitivity when including all eyes. Hence, our results suggest that among the evaluated measures of vision, contrast sensitivity is best correlated with the morphologic impairment in bilateral nAMD. Thus, contrast sensitivity may complement ETDRS visual acuity in clinical trials and serve as a standard diagnostic tool in clinical practice.
How to Optimize Treatment With Ustekinumab in Inflammatory Bowel Disease: Lessons Learned From Clinical Trials and Real-World Data
Authors: Gutiérrez Ana , Rodríguez-Lago Iago
Published: January 2021

Ustekinumab is a fully human IgG1 monoclonal antibody that has been approved for the treatment of moderate to severe Crohn's disease, and more recently moderate to severe ulcerative colitis. It binds with high affinity to the p40 subunit of human interleukin-12 and 23. This mechanism of action prevents the bioactivity of both interleukins, thus precluding their interaction with the cell surface receptor protein. The pivotal clinical trials (UNITI-1, UNITI-2 and IM-UNITI) demonstrated its clinical efficacy and safety, in naïve patients and also in those previously exposed to immunosuppressants and/or biologics. There is now an extensive experience with its use worldwide, corroborating its favorable profile even in patients with refractory disease. However, the number of medical treatment options available in inflammatory bowel disease are still limited. Hence, we should prioritize the treatments that have a greater probability of response in an individual patient. Our aim was to review and summarize all the available literature regarding the potential predictors of response to ustekinumab that can increase the success rate with this therapy in clinical practice.
Classification of the Zoonotic Hepatitis E Virus Genotype 3 Into Distinct Subgenotypes
Authors: Nicot Florence , Dimeglio Chloé , Migueres Marion , Jeanne Nicolas , Latour Justine , Abravanel Florence , Ranger Noémie , Harter Agnès , Dubois Martine , Lameiras Sonia , Baulande Sylvain , Chapuy-Regaud Sabine , Kamar Nassim , Lhomme Sébastien , Izopet Jacques
Published: January 2021

Hepatitis E virus (HEV) genotype 3 is the most common genotype linked to HEV infections in Europe and America. Three major clades (HEV-3.1, HEV-3.2, and HEV-3.3) have been identified but the overlaps between intra-subtype and inter-subtype p-distances make subtype classification inconsistent. Reference sequences have been proposed to facilitate communication between researchers and new putative subtypes have been identified recently. We have used the full or near full-length HEV-3 genome sequences available in the Genbank database (April 2020; n = 503) and distance analyses of clades HEV-3.1 and HEV-3.2 to determine a p-distance cut-off (0.093 nt substitutions/site) in order to define subtypes. This could help to harmonize HEV-3 genotyping, facilitate molecular epidemiology studies and investigations of the biological and clinical differences between HEV-3 subtypes.
White Matter Abnormalities in Patients With Parkinson's Disease: A Meta-Analysis of Diffusion Tensor Imaging Using Tract-Based Spatial Statistics
Authors: Wei Xia , Luo Chunyan , Li Qian , Hu Na , Xiao Yuan , Liu Nian , Lui Su , Gong Qiyong
Published: January 2021

Background:Tract-based spatial statistics (TBSS) studies based on diffusion tensor imaging (DTI) have revealed extensive abnormalities in white matter (WM) fibers of Parkinson's disease (PD); however, the results were inconsistent. Therefore, a meta-analytical approach was used in this study to find the most prominent and replicable WM abnormalities of PD.

Methods:Online databases were systematically searched for all TBSS studies comparing fractional anisotropy (FA) between patients with PD and controls. Subsequently, we performed the meta-analysis using a coordinate-based meta-analytic software called seed-based d mapping. Meanwhile, meta-regression was performed to explore the potential correlation between the alteration of FA and the clinical characteristics of PD.

Results:Out of a total of 1,701 studies that were identified, 23 studies were included. Thirty datasets, including 915 patients (543 men) with PD and 836 healthy controls (449 men), were included in the current study. FA reduction was identified in the body of the corpus callosum (CC; 245 voxels;z= −1.739;p< 0.001) and the left inferior fronto-occipital fasciculus (IFOF) 118 voxels;z= −1.182;p< 0.001). Both CC and IFOF maintained significance in the sensitivity analysis. No increase in FA was identified, but the percentage of male patients with PD was positively associated with the value of FA in the body of the CC.

Conclusions:Although some limitations exist, DTI is regarded as a valid way to identify the pathophysiology of PD. It could be more beneficial to integrate DTI parameters with other MRI techniques to explore brain degeneration in PD.
Nanomaterials Versus The Microbial Compounds With Wound Healing Property
Authors: Salimi Fatemeh , Mohammadipanah Fatemeh
Published: January 2021

Age and diabetes related slow-healing or chronic wounds may result in morbidity and mortality through persistent biofilms infections and prolonged inflammatory phase. Nano-materials [metal/metal oxide NPs (39%), lipid vehicles (21%), polymer NPs (19%), ceramic nanoparticles (NPs) (14%), and carbon nanomaterials (NMs) (7%)] can be introduced as a possible next-generation therapy because of either their intrinsic wound healing activity or via carrying bioactive compounds including, antibiotics, antioxidants, growth factor or stem cell. The nanomaterials have been shown to implicate in all four stages of wound healing including hemostasis (polymer NPs, ceramic NPs, nanoceria-6.1%), inflammation (liposome/vesicles/solid lipid NPs/polymer NPs/ceramic NPs/silver NPs/gold NPs/nanoceria/fullerenes/carbon-based NPs-32.7%), proliferation (vesicles/liposome/solid lipid NPs/gold NPs/silver NPs/iron oxide NPs/ceramic NPs/copper NPs/self-assembling elastin-like NPs/nanoceria/micelle/dendrimers/polymer NPs-57.1%), remodeling (iron oxide NPs/nanoceria-4.1%). Natural compounds from alkaloids, flavonoids, retinoids, volatile oil, terpenes, carotenoids, or polyphenolic compounds with proven antioxidant, anti-inflammatory, immunomodulatory, or antimicrobial characteristics are also well known for their potential to accelerate the wound healing process. In the current paper, we survey the potential and properties of nanomaterials and microbial compounds in improving the process of wound and scar healing. Finally, we review the potential biocompounds for incorporation to nano-material in perspective to designate more effective or multivalent wound healing natural or nano-based drugs.
Deep Brain Stimulation Initiative: Toward Innovative Technology, New Disease Indications, and Approaches to Current and Future Clinical Challenges in Neuromodulation Therapy
Authors: Sui Yanan , Tian Ye , Ko Wai Kin Daniel , Wang Zhiyan , Jia Fumin , Horn Andreas , De Ridder Dirk , Choi Ki Sueng , Bari Ausaf A. , Wang Shouyan , Hamani Clement , Baker Kenneth B. , Machado Andre G. , Aziz Tipu Z. , Fonoff Erich Talamoni , Kühn Andrea A. , Bergman Hagai , Sanger Terence , Liu Hesheng , Haber Suzanne N. , Li Luming
Published: January 2021

Deep brain stimulation (DBS) is one of the most important clinical therapies for neurological disorders. DBS also has great potential to become a great tool for clinical neuroscience research. Recently, the National Engineering Laboratory for Neuromodulation at Tsinghua University held an international Deep Brain Stimulation Initiative workshop to discuss the cutting-edge technological achievements and clinical applications of DBS. We specifically addressed new clinical approaches and challenges in DBS for movement disorders (Parkinson's disease and dystonia), clinical application toward neurorehabilitation for stroke, and the progress and challenges toward DBS for neuropsychiatric disorders. This review highlighted key developments in (1) neuroimaging, with advancements in 3-Tesla magnetic resonance imaging DBS compatibility for exploration of brain network mechanisms; (2) novel DBS recording capabilities for uncovering disease pathophysiology; and (3) overcoming global healthcare burdens with online-based DBS programming technology for connecting patient communities. The successful event marks a milestone for global collaborative opportunities in clinical development of neuromodulation to treat major neurological disorders.
An Inter- and Intra-Subject Transfer Calibration Scheme for Improving Feedback Performance of Sensorimotor Rhythm-Based BCI Rehabilitation
Authors: Cao Lei , Chen Shugeng , Jia Jie , Fan Chunjiang , Wang Haoran , Xu Zhixiong
Published: January 2021

The Brain Computer Interface (BCI) system is a typical neurophysiological application which helps paralyzed patients with human-machine communication. Stroke patients with motor disabilities are able to perform BCI tasks for clinical rehabilitation. This paper proposes an effective scheme of transfer calibration for BCI rehabilitation. The inter- and intra-subject transfer learning approaches can improve the low-precision classification performance for experimental feedback. The results imply that the systematical scheme is positive in increasing the confidence of voluntary training for stroke patients. In addition, it also reduces the time consumption of classifier calibration.
Alterations of Spinal Epidural Stimulation-Enabled Stepping by Descending Intentional Motor Commands and Proprioceptive Inputs in Humans With Spinal Cord Injury
Authors: Gill Megan L. , Linde Margaux B. , Hale Rena F. , Lopez Cesar , Fautsch Kalli J. , Calvert Jonathan S. , Veith Daniel D. , Beck Lisa A. , Garlanger Kristin L. , Sayenko Dimitry G. , Lavrov Igor A. , Thoreson Andrew R. , Grahn Peter J. , Zhao Kristin D.
Published: January 2021

Background: Regaining control of movement following a spinal cord injury (SCI) requires utilization and/or functional reorganization of residual descending, and likely ascending, supraspinal sensorimotor pathways, which may be facilitated via task-specific training through body weight supported treadmill (BWST) training. Recently, epidural electrical stimulation (ES) combined with task-specific training demonstrated independence of standing and stepping functions in individuals with clinically complete SCI. The restoration of these functions may be dependent upon variables such as manipulation of proprioceptive input, ES parameter adjustments, and participant intent during step training. However, the impact of each variable on the degree of independence achieved during BWST stepping remains unknown.

Objective: To describe the effects of descending intentional commands and proprioceptive inputs, specifically body weight support (BWS), on lower extremity motor activity and vertical ground reaction forces (vGRF) during ES-enabled BWST stepping in humans with chronic sensorimotor complete SCI. Furthermore, we describe perceived changes in the level of assistance provided by clinicians when intent and BWS are modified.

Methods: Two individuals with chronic, mid thoracic, clinically complete SCI, enrolled in an IRB and FDA (IDE G150167) approved clinical trial. A 16-contact electrode array was implanted in the epidural space between the T11-L1 vertebral regions. Lower extremity motor output and vertical ground reaction forces were obtained during clinician-assisted ES-enabled treadmill stepping with BWS. Consecutive steps were achieved during various experimentally-controlled conditions, including intentional participation and varied BWS (60% and 20%) while ES parameters remain unchanged.

Results: During ES-enabled BWST stepping, the knee extensors exhibited an increase in motor activation during trials in which stepping was passive compared to active or during trials in which 60% BWS was provided compared to 20% BWS. As a result of this increased motor activation, perceived clinician assistance increased during the transition from stance to swing. Intentional participation and 20% BWS resulted in timely and purposeful activation of the lower extremities muscles, which improved independence and decreased clinician assistance.

Conclusion: Maximizing participant intention and optimizing proprioceptive inputs through BWS during ES-enabled BWST stepping may facilitate greater independence during BWST stepping for individuals with clinically complete SCI.

Clinical Trial Registration:ClinicalTrials.gov identifier: NCT02592668.
The Physiological Significance of A-Waves in Early Diabetic Neuropathy: Assessment of Motor Nerve Fibers by Neurophysiological Techniques
Authors: Cai Qiong , Aimair Guliqiemu , Xu Wen-Xiao , Xiao Pei-Yao , Liu Lie-Hua , Liang Yin-Xing , Wu Chao , Liao Song-Jie
Published: January 2021

Objective: This study aimed to investigate how early A-waves could occur in type II diabetes, and what it implied functionally.

Methods: We performed conduction velocity distribution (CVD) test in peroneal nerves of 37 type II diabetic patients with normal nerve conduction study (NCS) and 22 age-matched controls. The electrophysiological data and clinical information were analyzed.

Results: A-waves were observed in 45.9% of diabetic patients and only in 1 person in healthy controls, all detected in the tibial nerves. The diabetic patients with A-waves showed faster conduction velocity in all quartiles in the motor peroneal nerves compared to the patients without A-waves, and their CVD histograms were shifted to the right side, consisting of a significantly larger percentage of fast conducting fibers. There was no significant difference in the CVD values of the upper extremity nerves among the patients with and without A-waves and the healthy controls.

Conclusion: A-waves could occur in type II diabetes as early as when NCS showed normal, and represented as a sign of neuropathy as well as a sign of rescued motor nerve function.
Patterns of Presentation of SARS-CoV-2 Infection in Children. Experience at the Italian Epicentre of the Pandemic
Authors: Mazza Angelo , Di Giorgio Angelo , Martelli Laura , Pelliccia Ciretta , Pinotti Moira Alessandra , Quadri Vera , Verdoni Lucio , Decio Alice , Ruggeri Maurizio , D'Antiga Lorenzo
Published: January 2021

Background: COVID-19, a disease caused by the new coronavirus SARS-CoV-2, spread worldwide, and Bergamo was one of the most affected areas in Europe. Following the first outbreak, more than half of the population of the Bergamo province had been infected. We aimed to describe the patients admitted to our unit shortly after the first outbreak.

Methods: we retrospectively reviewed the notes of all pediatric patients diagnosed with COVID-19. We enrolled patients with positive swabs or serology and classified them based on the pattern and the timing of presentation after the first outbreak. This setting was considered a reliable reflection of the consequences of unmitigated SARS-CoV-2 circulation.

Results: We diagnosed 35 patients over a 3-month period and we identified six patterns presenting in two temporal phases: Early phase, Group 1 (median of 20 days from epidemic start, IQR: 15–27): neonatal sepsis (n.7), pneumonia (n.5), flu-like symptoms (n.2). Late phase, Group 2 (59:51–66 days, p < 0.001): MIS-C (n.18), neurological manifestations (n.3). Group 1 differed from Group 2 for younger age (1 vs. 8 years, p = 0.02), lower C-reactive protein (0.9 vs. 16.6 mg/dl, p = 0.008), procalcitonin (0.16 vs. 7.9 ng/ml, p = 0.008) and neutrophil count (3,765 vs. 6,780/μl, p = 0.006), higher rate of positive swabs (14/14 vs. 9/21, p < 0.001), higher lymphocyte count (3,000 vs. 930/μl, p = 0.006) and platelet count (323,000 vs. 210,000/μl, p = 0.009).

Conclusions: Following an outbreak of unmitigated SARS-CoV-2 diffusion, infected children may present with clinical patterns suggesting two temporal clusters, the first characterized by markers of direct viral injury, the second suggesting an immune-mediated disease.
The Breast Cancer Stem Cells Traits and Drug Resistance
Authors: Zheng Qinghui , Zhang Mengdi , Zhou Fangfang , Zhang Long , Meng Xuli
Published: January 2021

Drug resistance is a major challenge in breast cancer (BC) treatment at present. Accumulating studies indicate that breast cancer stem cells (BCSCs) are responsible for the BC drugs resistance, causing relapse and metastasis in BC patients. Thus, BCSCs elimination could reverse drug resistance and improve drug efficacy to benefit BC patients. Consequently, mastering the knowledge on the proliferation, resistance mechanisms, and separation of BCSCs in BC therapy is extremely helpful for BCSCs-targeted therapeutic strategies. Herein, we summarize the principal BCSCs surface markers and signaling pathways, and list the BCSCs-related drug resistance mechanisms in chemotherapy (CT), endocrine therapy (ET), and targeted therapy (TT), and display therapeutic strategies for targeting BCSCs to reverse drug resistance in BC. Even more importantly, more attention should be paid to studies on BCSC-targeted strategies to overcome the drug resistant dilemma of clinical therapies in the future.
Population Pharmacokinetic Analysis of Yimitasvir in Chinese Healthy Volunteers and Patients With Chronic Hepatitis C Virus Infection
Authors: Guan Xiao-duo , Tang Xian-ge , Zhang Ying-jun , Xie Hong-ming , Luo Lin , Wu Dan , Chen Rui , Hu Pei
Published: January 2021

Yimitasvir is a novel, oral hepatitis C virus (HCV) non-structural protein 5A inhibitor for the treatment of chronic HCV genotype 1 infection. The objective of this analysis was to develop a population pharmacokinetic model of yimitasvir in Chinese healthy volunteers and HCV infection patients. The model was performed using data from 219 subjects across six studies. Nonlinear mixed effects models were developed using Phoenix NLME software. The covariates were evaluated using a stepwise forward inclusion (p < 0.01) and then a backward exclusion procedure (p < 0.001). A two-compartment model with sequential zero-first order absorption and first-order elimination reasonably described yimitasvir pharmacokinetics (PK). The apparent oral clearance and central volume of distribution were 13.8 l·h−1 and 188 l, respectively. The bioavailability (F) of yimitasvir decreased 12.9% for each 100 mg dose increase. Food was found to affect absorption rate (Ka) and F. High-fat meal decreased Ka and F by 90.9% and 38.5%, respectively. Gender and alanine aminotransferase were identified as significant covariates on apparent oral clearance. Female subjects had lower clearance than male subjects. Zero-order absorption duration was longer in healthy volunteers (2.17 h) than that in patients (1.43 h). The population pharmacokinetic model described yimitasvir PK profile well. Food decreased Ka and F significantly, so it was recommended to take yimitasvir at least 2 h before or after a meal. Other significant covariates were not clinically important.
Induced Expression of kir6.2 in A1 Astrocytes Propagates Inflammatory Neurodegeneration via Drp1-dependent Mitochondrial Fission
Authors: Song Nanshan , Zhu Hong , Xu Rong , Liu Jiaqi , Fang Yinquan , Zhang Jing , Ding Jianhua , Hu Gang , Lu Ming
Published: January 2021

Glia-mediated inflammatory processes are crucial in the pathogenesis of Parkinson’s disease (PD). As the most abundant cells of the brain and active participants in neuroinflammatory responses, astrocytes largely propagate inflammatory signals and amplify neuronal loss. Hence, intensive control of astrocytic activation is necessary to prevent neurodegeneration. In this study, we report that the astrocytic kir6.2, as a abnormal response after inflammatory stimuli, promotes the reactivity of A1 neurotoxic astrocytes. Using kir6.2 knockout (KO) mice, we find reversal effects of kir6.2 deficiency on A1-like astrocyte activation and death of dopaminergic neurons in lipopolysaccharide (LPS)-induced mouse models for PD. Further in vitro experiments show that aberrant kir6.2 expression induced by inflammatory irritants in astrocytes mediates the dynamin-related protein 1 (Drp1)-dependent excessive mitochondrial fragmentation and results in mitochondrial malfunctions. By deleting kir6.2, astrocytic activation is reduced and astrocytes-derived neuronal injury is prevented. We therefore conclude that astrocytic kir6.2 can potentially elucidate the pathology of PD and promote the development of therapeutic strategies for PD.
Carveol a Naturally-Derived Potent and Emerging Nrf2 Activator Protects Against Acetaminophen-Induced Hepatotoxicity
Authors: Rahman Zaif Ur , Al Kury Lina Tariq , Alattar Abdullah , Tan Zhen , Alshaman Reem , Malik Imran , Badshah Haroon , Uddin Zia , Khan Khalil Atif Ali , Muhammad Naveed , Khan Saifullah , Ali Amjad , Shah Fawad Ali , Li Jing Bo , Li Shupeng
Published: January 2021

Acetaminophen (N-acetyl p-aminophenol or APAP) is used worldwide for its antipyretic and anti-inflammatory potential. However, APAP overdose sometimes causes severe liver damage. In this study, we elucidated the protective effects of carveol in liver injury, using molecular and in silico approaches. Male BALB/c mice were divided into two experimental cohorts, to identify the best dose and to further assess the role of carveol in the nuclear factor E2-related factor; nuclear factor erythroid 2; p45-related factor 2 (Nrf2) pathway. The results demonstrated that carveol significantly modulated the detrimental effects of APAP by boosting endogenous antioxidant mechanisms, such as nuclear translocation of Nrf2 gene, a master regulator of the downstream antioxidant machinery. Furthermore, an inhibitor of Nrf2, called all-trans retinoic acid (ATRA), was used, which exaggerated APAP toxicity, in addition to abrogating the protective effects of carveol; this effect was accompanied by overexpression of inflammatory mediators and liver = 2ltoxicity biomarkers. To further support our notion, we performed virtual docking of carveol with Nrf2-keap1 target, and the resultant drug-protein interactions validated the in vivo findings. Together, our findings suggest that carveol could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating the APAP-induced inflammation and oxidative stress.
Dependence of Connectivity on the Logarithm of Geometric Distance in Brain Networks
Authors: Castelluzzo Michele , Perinelli Alessio , Tabarelli Davide , Ricci Leonardo
Published: January 2021

Physical connections between nodes in a complex network are constrained by limiting factors, such as the cost of establishing links and maintaining them, which can hinder network capability in terms of signal propagation speed and processing power. Trade-off mechanisms between cost constraints and performance requirements are reflected in the topology of a network and, ultimately, on the dependence of connectivity on geometric distance. This issue, though rarely addressed, is crucial in neuroscience, where physical links between brain regions are associated with a metabolic cost. In this work we investigate brain connectivity—estimated by means of a recently developed method that evaluates time scales of cross-correlation observability—and its dependence on geometric distance by analyzing resting state magnetoencephalographic recordings collected from a large set of healthy subjects. We identify three regimes of distance each showing a specific behavior of connectivity. This identification makes up a new tool to study the mechanisms underlying network formation and sustainment, with possible applications to the investigation of neuroscientific issues, such as aging and neurodegenerative diseases.
Co-inhibition of CD73 and ADORA2B Improves Long-Term Cigarette Smoke Induced Lung Injury
Authors: Tian Zhi , Dixon Jendayi , Guo Xiaofang , Deal Benjamin , Liao Qianjin , Zhou Yujuan , Cheng Feng , Allen-Gipson Diane S.
Published: January 2021

Adenosine (ADO) involvement in lung injury depends on the activation of its receptors. The ADO A2A receptor (ADORA2A) and A2B receptor (ADORA2B) are best described to have both tissue-protective and tissue-destructive processes. However, no approach has been effective in delineating the mechanism(s) involved with ADO shifting from its tissue-protective to tissue-destructive properties in chronic airway injury. Using cigarette smoke (CS) as our model of injury, we chronically exposed Nuli-1 cells to 5% CS extract (CSE) for 3 years establishing a long-term CSE exposure model (LTC). We found significant morphological changes, decreased proliferation, and migration resulting in impaired airway wound closure in LTC. Further investigations showed that long-term CSE exposure upregulates CD73 and ADORA2B expression, increases ADO production, inhibits PKC alpha activity and p-ERK signaling pathway. Knocking down ADORA2B and/or CD73 in LTC activates PKC alpha and increases p-ERK signaling. Knocking down both showed better improvement in wound repair than either alone. In vivo experiments also showed that double knockout CD73 and ADORA2B remarkably improved CS-induced lung injury by activating PKC alpha, reducing the inflammatory cell number in bronchoalveolar lavage fluid and the production of inflammatory mediator IL-6, inhibiting the fibrosis-like lesions and decreasing collagen deposition surrounding bronchioles. Collectively, long-term CSE exposure upregulates CD73 expression and increases ADO production, which promotes low affinity ADORA2B activation and subsequent diminution of PKC alpha activity and ERK signaling pathway, and inhibition of airway wound repair. Moreover, the data suggesting ADORA2B and CD73 as potential therapeutic targets may be more efficacious in improving chronic CS lung diseases and impaired wound repair.
Effects of Ultramarathon Running on Mitochondrial Function of Platelets and Oxidative Stress Parameters: A Pilot Study
Authors: Hoppel Florian , Calabria Elisa , Pesta Dominik H. , Kantner-Rumplmair Wilhelm , Gnaiger Erich , Burtscher Martin
Published: January 2021

Only a few studies have evaluated changes in mitochondrial function and oxidative stress associated with ultramarathon running. Invasive biopsies are needed to assess mitochondrial function of skeletal muscle, which may not be well tolerated by some individuals. Platelets (PLTs) as a metabolically highly active and homogenous cell population were suggested as a potentially valuable surrogate to investigate mitochondrial function. Thus, this study was aimed to evaluate mitochondrial function of PLTs and its association with individual race performance and markers of oxidative stress, muscle damage and renal dysfunction. Race performance and mitochondrial function (high-resolution respirometry, HRR) of PLTs using different substrates inducing ROUTINE, LEAK, N-pathway control state (Complex I linked oxidative phosphorylation; CI, OXPHOS), NS-pathway control state (CI + II linked OXPHOS and electron transfer pathway; ET), S-pathway control state (CII linked ET) as well as parameters of oxidative stress and antioxidant capacity, and markers of muscle and renal injury were assessed in eight male ultramarathon runners (26–45 years) before, immediately after and 24 h after an ultramarathon race (PRE, POST, and REC). Ultramarathon running induced an increase in LEAK O2 flux of PLT mitochondria and slight, largely non-significant changes in the oxidant/antioxidant balance. Levels of creatine kinase (CK), lactate dehydrogenase (LDH), blood urea nitrogen, and creatinine were all significantly elevated POST and remained high in REC. There were inverse correlations between race time and N-linked substrate state PRE-POST, and changes in CK and LDH levels were significantly related to PLT mitochondrial LEAK and N-linked respiration PRE. Although race-related changes in respirometry parameters of PLT mitochondria were rather small, a somewhat more pronounced increase in the relative N-linked respiration in faster runners might suggest PLT CI as indicator of physical fitness. The higher PLT LEAK PRE and diminished increase of CK during the race may represent a prophylactic preconditioning and the slight but non-significant elevation of the antioxidant potential post-race as a protective consequence of the race-related oxidative stress and potential threat to the kidney. Our findings point toward an interrelationship between mitochondrial function of PLTs, individual fitness levels and extreme physical and metal stresses, which stimulates further research.
siRNA Specificity: RNAi Mechanisms and Strategies to Reduce Off-Target Effects
Authors: Neumeier Julia , Meister Gunter
Published: January 2021

Short interfering RNAs (siRNAs) are processed from long double-stranded RNA (dsRNA), and a guide strand is selected and incorporated into the RNA-induced silencing complex (RISC). Within RISC, a member of the Argonaute protein family directly binds the guide strand and the siRNA guides RISC to fully complementary sites on-target RNAs, which are then sequence-specifically cleaved by the Argonaute protein—a process commonly referred to as RNA interference (RNAi). In animals, endogenous microRNAs (miRNAs) function similarly but do not lead to direct cleavage of the target RNA but to translational inhibition followed by exonucleolytic decay. This is due to only partial complementarity between the miRNA and the target RNA. SiRNAs, however, can function as miRNAs, and partial complementarity can lead to miRNA-like off-target effects in RNAi applications. Since siRNAs are widely used not only for screening but also for therapeutics as well as crop protection purposes, such miRNA-like off-target effects need to be minimized. Strategies such as RNA modifications or pooling of siRNAs have been developed and are used to reduce off-target effects.
Mechanisms Regulating the Dynamics of Photosynthesis Under Abiotic Stresses
Authors: Muhammad Izhar , Shalmani Abdullah , Ali Muhammad , Yang Qing-Hua , Ahmad Husain , Li Feng Bai
Published: January 2021

Photosynthesis sustains plant life on earth and is indispensable for plant growth and development. Factors such as unfavorable environmental conditions, stress regulatory networks, and plant biochemical processes limits the photosynthetic efficiency of plants and thereby threaten food security worldwide. Although numerous physiological approaches have been used to assess the performance of key photosynthetic components and their stress responses, though, these approaches are not extensive enough and do not favor strategic improvement of photosynthesis under abiotic stresses. The decline in photosynthetic capacity of plants due to these stresses is directly associated with reduction in yield. Therefore, a detailed information of the plant responses and better understanding of the photosynthetic machinery could help in developing new crop plants with higher yield even under stressed environments. Interestingly, cracking of signaling and metabolic pathways, identification of some key regulatory elements, characterization of potential genes, and phytohormone responses to abiotic factors have advanced our knowledge related to photosynthesis. However, our understanding of dynamic modulation of photosynthesis under dramatically fluctuating natural environments remains limited. Here, we provide a detailed overview of the research conducted on photosynthesis to date, and highlight the abiotic stress factors (heat, salinity, drought, high light, and heavy metal) that limit the performance of the photosynthetic machinery. Further, we reviewed the role of transcription factor genes and various enzymes involved in the process of photosynthesis under abiotic stresses. Finally, we discussed the recent progress in the field of biodegradable compounds, such as chitosan and humic acid, and the effect of melatonin (bio-stimulant) on photosynthetic activity. Based on our gathered researched data set, the logical concept of photosynthetic regulation under abiotic stresses along with improvement strategies will expand and surely accelerate the development of stress tolerance mechanisms, wider adaptability, higher survival rate, and yield potential of plant species.
Protein Farnesylation Takes Part in Arabidopsis Seed Development
Authors: Vergès Valentin , Dutilleul Christelle , Godin Béatrice , Collet Boris , Lecureuil Alain , Rajjou Loïc , Guimaraes Cyrille , Pinault Michelle , Chevalier Stéphane , Giglioli-Guivarc’h Nathalie , Ducos Eric
Published: January 2021

Protein farnesylation is a post-translational modification regulated by theERA1(Enhanced Response to ABA 1) gene encoding the β-subunit of the protein farnesyltransferase in Arabidopsis. Theera1mutants have been described for over two decades and exhibit severe pleiotropic phenotypes, affecting vegetative and flower development. We further investigated the development and quality ofera1seeds. While theera1ovary contains numerous ovules, the plant produces fewer seeds but larger and heavier, with higher protein contents and a modified fatty acid distribution. Furthermore,era1pollen grains show lower germination rates and, at flower opening, the pistils are immature and the ovules require one additional day to complete the embryo sac. Hand pollinated flowers confirmed that pollination is a major obstacle toera1seed phenotypes, and a near wild-type seed morphology was thus restored. Still,era1seeds conserved peculiar storage protein contents and altered fatty acid distributions. The multiplicity ofera1phenotypes reflects the diversity of proteins targeted by the farnesyltransferase. Our work highlights the involvement of protein farnesylation in seed development and in the control of traits of agronomic interest.
Improving Nitrogen Use Efficiency Through Overexpression of Alanine Aminotransferase in Rice, Wheat, and Barley
Authors: Tiong Jingwen , Sharma Niharika , Sampath Ramya , MacKenzie Nenah , Watanabe Sayuri , Metot Claire , Lu Zhongjin , Skinner Wayne , Lu Yingzhi , Kridl Jean , Baumann Ute , Heuer Sigrid , Kaiser Brent , Okamoto Mamoru
Published: January 2021

Nitrogen is an essential nutrient for plants, but crop plants are inefficient in the acquisition and utilization of applied nitrogen. This often results in producers over applying nitrogen fertilizers, which can negatively impact the environment. The development of crop plants with more efficient nitrogen usage is, therefore, an important research goal in achieving greater agricultural sustainability. We utilized genetically modified rice lines over-expressing a barley alanine aminotransferase (HvAlaAT) to help characterize pathways which lead to more efficient use of nitrogen. Under the control of a stress-inducible promoter OsAnt1, OsAnt1:HvAlaAT lines have increased above-ground biomass with little change to both nitrate and ammonium uptake rates. Based on metabolic profiles, carbon metabolites, particularly those involved in glycolysis and the tricarboxylic acid (TCA) cycle, were significantly altered in roots of OsAnt1:HvAlaAT lines, suggesting higher metabolic turnover. Moreover, transcriptomic data revealed that genes involved in glycolysis and TCA cycle were upregulated. These observations suggest that higher activity of these two processes could result in higher energy production, driving higher nitrogen assimilation, consequently increasing biomass production. Other potential mechanisms contributing to a nitrogen-use efficient phenotype include involvements of phytohormonal responses and an alteration in secondary metabolism. We also conducted basic growth studies to evaluate the effect of the OsAnt1:HvAlaAT transgene in barley and wheat, which the transgenic crop plants increased seed production under controlled environmental conditions. This study provides comprehensive profiling of genetic and metabolic responses to the over-expression of AlaAT and unravels several components and pathways which contribute to its nitrogen-use efficient phenotype.
Wheat Can Access Phosphorus From Algal Biomass as Quickly and Continuously as From Mineral Fertilizer
Authors: Mau Lisa , Kant Josefine , Walker Robert , Kuchendorf Christina M. , Schrey Silvia D. , Roessner Ute , Watt Michelle
Published: January 2021

Algae can efficiently take up excess nutrients from waterways, making them a valuable resource potentially capable of replacing synthesized and mined fertilizers for agriculture. The capacity of algae to fertilize crops has been quantified, but it is not known how the algae-derived nutrients become available to plants. We aimed to address this question: what are the temporal dynamics of plant growth responses to algal biomass? to better propose mechanisms by which plants acquire nutrients from algal biomass and thereby study and promote those processes in future agricultural applications. Data from various sources were transformed and used to reconstruct the nutrient release from the algae Chlorella vulgaris and subsequent uptake by wheat (Triticum aestivum L.) (as reported in Schreiber et al., 2018). Plants had received 0.1x or 1x dried algae or wet algae, or zero, 0.1x or 1x mineral fertilizer calculated from agricultural practices for P application and grown to 55 days in three soils. Contents of P and other nutrients acquired from algae were as high as from mineral fertilizer, but varied based on moisture content and amount of algae applied to soils (by 55 days after sowing plants with 1x mineral fertilizer and 1x dried algae had 5.6 mg P g DWshoot; 2.2-fold more than those with 0 or 0.1x mineral fertilizer, 0.1x dried algae and wet algae, and 1x wet algae). Absolute and relative leaf area growth and estimated P uptake rates showed similar dynamics, indicating that wheat acquires P from algae quickly. A model proposes that algal fertilizer promotes wheat growth after rapid transformation in soil to inorganic nutrients. We conclude theoretically that phosphorus from algal biomass is available to wheat seedlings upon its application and is released gradually over time with minor differences related to moisture content on application. The growth and P uptake kinetics hint at nutrient forms, including N, and biomass stimulation worthy of research to further exploit algae in sustainable agriculture practices. Temporal resolved phenotype analyses in combination with a mass-balance approach is helpful for understanding resource uptake from recycled and biofertilizer sources by plants.
How Do Voters Perceive Disabled Candidates?
Authors: Reher Stefanie
Published: January 2021

In order to form an impression of the traits, views, and competencies of election candidates, voters often draw on existing stereotypes about their identities and characteristics, such as their gender or ethnicity. Meanwhile, although there is a strong stigma associated with disability in our societies, we know very little about how voters perceive candidates with disabilities. This study uses a survey experiment with a conjoint design conducted in Britain to examine the effects of candidate disability on voter perceptions of their personality traits, beliefs, and issue competencies. Contrary to common stereotypes, physically disabled candidates are not seen as incompetent and weak. Instead, they are perceived as more compassionate, honest, and hard-working than nondisabled candidates, although the effects are modest in size. They are also assumed to be further to the left ideologically and more concerned about and competent in dealing with policy on healthcare, minority rights, and social welfare. The study enriches our understanding of the role of disability in electoral behavior and political representation while also providing valuable—and overall encouraging—insights for disabled (aspiring) politicians and political parties.
Framing Messages to Deal With the COVID-19 Crisis: The Role of Loss/Gain Frames and Content
Authors: Gantiva Carlos , Jiménez-Leal William , Urriago-Rayo Joan
Published: January 2021

The goal of this study was to test the role of message framing for effective communication of self-care behaviors in the context of the COVID-19 pandemic, contrasting health and economic-focused messages. We presented 319 participants with an unforced choice task where they had to select the message that they believed was more effective to increase intentions toward self-care behaviors, motivate self-care behaviors in others, increase perceived risk and enhance perceived message strength. Results showed that gain-frame health messages increased intention to adopt self-care behaviors and were judged to be stronger. Loss-framed health messages increased risk perception. When judging effectiveness for others, participants believed other people would be more sensitive to messages with an economic focus. These results can be used by governments to guide communication for the prevention of COVID-19 contagion in the media and social networks, where time and space for communicating information are limited.
Ambivalent Food Craving and Psychobiological Characteristics in Individuals With Weight Suppression
Authors: Lee Mooah , Lee Jang-Han
Published: January 2021

This study investigated the effects of psychobiological characteristics of non-obese women with a high level of weight suppression (H-WS) on explicit-implicit and approach-avoidance response toward food cues, depending on hunger-satiety states. The 634 participants were divided into two groups according to their weight history. If the difference between their highest weight over the last year and their current weight (a difference sustained at least for 1 year) was more than 5%, they were assigned to the “H-WS” group (N= 25). If the difference in weight was less than 5%, they were assigned to the “low level of weight suppression” (L-WS) group (N= 29). Explicit approach and avoidance toward food were measured by self-report questionnaires. Implicit approach and avoidance toward food cues were measured using an eye-tracker. Fasting blood samples were obtained to measure fasting serum leptin levels. After this, participants consumed a standard breakfast to control the satiety level. After breakfast, explicit-implicit approach-avoidance responses were repeatedly measured at the satiety states. Self-reported body shape concerns, drive for thinness, ambivalent food craving, and bulimic behavior were also assessed. The results showed that the H-WS group had lower leptin levels, and higher body shape concerns, drive for thinness, ambivalent food craving, and bulimic behaviors compared to the L-WS group. At the explicit level, the H-WS group reported lower approach and higher avoidance to food compared to the L-WS group, regardless of hunger-satiety state. Whereas, at the implicit level, the H-WS group showed higher approach during satiety rather than during hunger states. Regardless of the hunger-satiety state, there were no significant group differences with regard to implicit avoidance between the two groups. Thus, we confirmed that a high level of avoidance toward foods was observed in the H-WS group at the explicit level but not at the implicit level. Moreover, in contrast with a high level of explicit avoidance toward palatable foods, inhibition for implicit approach toward high-calorie foods seemed to be blunted after food consumption in the H-WS group. These inconsistencies may be associated with ambivalent food craving and vulnerability to bulimic behavior among H-WS individuals.
Eliciting End-State Comfort Planning in Children With and Without Developmental Coordination Disorder Using a Hammer Task: A Pilot Study
Authors: Krajenbrink Hilde , Lust Jessica Mireille , Steenbergen Bert
Published: January 2021

The end-state comfort (ESC) effect refers to the consistent tendency of healthy adults to end their movements in a comfortable end posture. In children with and without developmental coordination disorder (DCD), the results of studies focusing on ESC planning have been inconclusive, which is likely to be due to differences in task constraints. The present pilot study focused on the question whether children with and without DCD were able to change their planning strategy and were more likely to plan for ESC when demanded by complex object manipulations at the end of a task. To this end, we examined ESC planning in 18 children with and without DCD (aged 5–11years) using the previously used sword-task and the newly developed hammer-task. In the sword-task, children had to insert a sword in a wooden block, which could be relatively easily completed with an uncomfortable end-posture. In the hammer-task, children had to strike down a nail in a wooden pounding bench, which required additional force and speed demands, making it relatively difficult to complete the movement with an uncomfortable end-posture. In line with our hypothesis, the results demonstrated that children with and without DCD were more likely to plan for ESC on the hammer-task compared with the sword-task. Thus, while children with and without DCD show inconsistent ESC planning on many previously used tasks, the present pilot study shows that many of them are able to take into account the end-state of their movements if demanded by task constraints.
Does Social Exclusion Improve Detection of Real and Fake Smiles? A Replication Study
Authors: Schindler Simon , Trede Martin
Published: January 2021

Research on social exclusion suggests an increased attention of excluded persons to subtle social cues. In one study (N= 32), published inPsychological Science,Bernstein et al. (2008)provided evidence for this idea by showing that participants in the social exclusion condition were better in correctly categorizing a target person’s smile as real or fake. Although highly cited, this finding has never been directly replicated. The present study aimed to fill that gap. 201 participants (79.1% female) were randomly assigned to a social exclusion, social inclusion or control condition. Next, participants watched 20 videos of smiling persons and rated whether they show a real or a fake smile. In line with the original study, results showed that participants in the exclusion condition performed better than in the control condition. However, the performance did not differ between the exclusion and inclusion condition—although the pattern was in the predicted direction. In sum, the findings of our study increase rather than decrease confidence in the validity of the investigated idea, but results point to a substantially smaller effect.