bluuebunny/crossref_metadata_2025 huggingface dataset:
CaFtsH06, A Novel Filamentous Thermosensitive Protease Gene, Is Involved in Heat, Salt, and Drought Stress Tolerance of Pepper (Capsicum annuum L.)
Authors: Xiao Jing-Jing , Zhang Rui-Xing , Khan Abid , ul Haq Saeed , Gai Wen-Xian , Gong Zhen-Hui
Published: June 2021

Harsh environmental factors have continuous negative effects on plant growth and development, leading to metabolic disruption and reduced plant productivity and quality. However, filamentation temperature-sensitive H protease (FtsH) plays a prominent role in helping plants to cope with these negative impacts. In the current study, we examined the transcriptional regulation of the CaFtsH06 gene in the R9 thermo-tolerant pepper (Capsicum annuum L.) line. The results of qRT-PCR revealed that CaFtsH06 expression was rapidly induced by abiotic stress treatments, including heat, salt, and drought. The CaFtsH06 protein was localized to the mitochondria and cell membrane. Additionally, silencing CaFtsH06 increased the accumulation of malonaldehyde content, conductivity, hydrogen peroxide (H2O2) content, and the activity levels of superoxide dismutase and superoxide (·O2−), while total chlorophyll content decreased under these abiotic stresses. Furthermore, CaFtsH06 ectopic expression enhanced tolerance to heat, salt, and drought stresses, thus decreasing malondialdehyde, proline, H2O2, and ·O2− contents while superoxide dismutase activity and total chlorophyll content were increased in transgenic Arabidopsis. Similarly, the expression levels of other defense-related genes were much higher in the transgenic ectopic expression lines than WT plants. These results suggest that CaFtsH06 confers abiotic stress tolerance in peppers by interfering with the physiological indices through reducing the accumulation of reactive oxygen species, inducing the activities of stress-related enzymes and regulating the transcription of defense-related genes, among other mechanisms. The results of this study suggest that CaFtsH06 plays a very crucial role in the defense mechanisms of pepper plants to unfavorable environmental conditions and its regulatory network with other CaFtsH genes should be examined across variable environments.
Alternative Promoter Use Governs the Expression of IgLON Cell Adhesion Molecules in Histogenetic Fields of the Embryonic Mouse Brain
Authors: Jagomäe Toomas , Singh Katyayani , Philips Mari-Anne , Jayaram Mohan , Seppa Kadri , Tekko Triin , Gilbert Scott F. , Vasar Eero , Lilleväli Kersti
Published: June 2021

The members of the IgLON superfamily of cell adhesion molecules facilitate fundamental cellular communication during brain development, maintain functional brain circuitry, and are associated with several neuropsychiatric disorders such as depression, autism, schizophrenia, and intellectual disabilities. Usage of alternative promoter-specific 1a and 1b mRNA isoforms in Lsamp, Opcml, Ntm, and the single promoter of Negr1 in the mouse and human brain has been previously described. To determine the precise spatiotemporal expression dynamics of Lsamp, Opcml, Ntm isoforms, and Negr1, in the developing brain, we generated isoform-specific RNA probes and carried out in situ hybridization in the developing (embryonic, E10.5, E11.5, 13.5, 17; postnatal, P0) and adult mouse brains. We show that promoter-specific expression of IgLONs is established early during pallial development (at E10.5), where it remains throughout its differentiation through adulthood. In the diencephalon, midbrain, and hindbrain, strong expression patterns are initiated a few days later and begin fading after birth, being only faintly expressed during adulthood. Thus, the expression of specific IgLONs in the developing brain may provide the means for regionally specific functionality as well as for specific regional vulnerabilities. The current study will therefore improve the understanding of how IgLON genes are implicated in the development of neuropsychiatric disorders.
TENT4A Non-Canonical Poly(A) Polymerase Regulates DNA-Damage Tolerance via Multiple Pathways That Are Mutated in Endometrial Cancer
Authors: Swain Umakanta , Friedlander Gilgi , Sehrawat Urmila , Sarusi-Portuguez Avital , Rotkopf Ron , Ebert Charlotte , Paz-Elizur Tamar , Dikstein Rivka , Carell Thomas , Geacintov Nicholas E. , Livneh Zvi
Published: June 2021

TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here, we show that TENT4A regulates multiple biological pathways and focuses on its multilayer regulation of translesion DNA synthesis (TLS), in which error-prone DNA polymerases bypass unrepaired DNA lesions. We show that TENT4A regulates mRNA stability and/or translation of DNA polymerase η and RAD18 E3 ligase, which guides the polymerase to replication stalling sites and monoubiquitinates PCNA, thereby enabling recruitment of error-prone DNA polymerases to damaged DNA sites. Remarkably, in addition to the effect on RAD18 mRNA stability via controlling its poly(A) tail, TENT4A indirectly regulates RAD18 via the tumor suppressor CYLD and via the long non-coding antisense RNA PAXIP1-AS2, which had no known function. Knocking down the expression of TENT4A or CYLD, or overexpression of PAXIP1-AS2 led each to reduced amounts of the RAD18 protein and DNA polymerase η, leading to reduced TLS, highlighting PAXIP1-AS2 as a new TLS regulator. Bioinformatics analysis revealed that TLS error-prone DNA polymerase genes and their TENT4A-related regulators are frequently mutated in endometrial cancer genomes, suggesting that TLS is dysregulated in this cancer.
Level of Murine DDX3 RNA Helicase Determines Phenotype Changes of Hepatocytes In Vitro and In Vivo
Authors: Sergeeva Olga , Abakumova Tatiana , Kurochkin Ilia , Ialchina Renata , Kosyreva Anna , Prikazchikova Tatiana , Varlamova Varvara , Shcherbinina Evgeniya , Zatsepin Timofei
Published: June 2021

DDX3 RNA helicase is intensively studied as a therapeutic target due to participation in the replication of some viruses and involvement in cancer progression. Here we used transcriptome analysis to estimate the primary response of hepatocytes to different levels of RNAi-mediated knockdown of DDX3 RNA helicase both in vitro and in vivo. We found that a strong reduction of DDX3 protein (>85%) led to similar changes in vitro and in vivo—deregulation of the cell cycle and Wnt and cadherin pathways. Also, we observed the appearance of dead hepatocytes in the healthy liver and a decrease of cell viability in vitro after prolonged treatment. However, more modest downregulation of the DDX3 protein (60–65%) showed discordant results in vitro and in vivo—similar changes in vitro as in the case of strong knockdown and a different phenotype in vivo. These results demonstrate that the level of DDX3 protein can dramatically influence the cell phenotype in vivo and the decrease of DDX3, for more than 85% leads to cell death in normal tissues, which should be taken into account during the drug development of DDX3 inhibitors.
Extracellular Vesicles (Secretomes) from Human Trophoblasts Promote the Regeneration of Skin Fibroblasts
Authors: Go Yoon Young , Lee Chan Mi , Ju Won Min , Chae Sung-Won , Song Jae-Jun
Published: June 2021

To date, placental trophoblasts have been of interest in the fields of obstetrics and gynecology, mainly due to their involvement in the formation of a connection between the mother and fetus that aids in placental development and fetal survival. However, the regenerative capacities of trophoblasts for application in regenerative medicine and tissue engineering are poorly understood. Here, we aim to determine the skin regeneration and anti-aging capacities of trophoblast-derived conditioned medium (TB-CM) and exosomes (TB-Exos) using human normal dermal fibroblasts (HNDFs). TB-CM and TB-Exos treatments significantly elevated the migration and proliferation potencies of HNDF cells in a dose- and time-dependent manner. When RNA sequencing (RNA-seq) was used to investigate the mechanism underlying TB-CM-induced cell migration on scratch-wounded HNDFs, the increased expression of genes associated with C-X-C motif ligand (CXCL) chemokines, toll-like receptors, and nuclear factor-kappa B (NF-κB) signaling was observed. Furthermore, treatment of intrinsically/extrinsically senescent HNDFs with TB-CM resulted in an enhanced rejuvenation of HNDFs via both protection and restoration processes. Gene expression of extracellular matrix components in the skin dermis significantly increased in TB-CM- and TB-Exos-treated HNDFs. These components are involved in the TB-CM and Exo-mediated regeneration and anti-aging of HNDFs. Thus, this study demonstrated the regenerative and anti-aging efficacies of trophoblast-derived secretomes, suggesting their potential for use in interventions for skin protection and treatment.
Non-Genetic Diversity in Chemosensing and Chemotactic Behavior
Authors: Moore Jeremy Philippe , Kamino Keita , Emonet Thierry
Published: June 2021

Non-genetic phenotypic diversity plays a significant role in the chemotactic behavior of bacteria, influencing how populations sense and respond to chemical stimuli. First, we review the molecular mechanisms that generate phenotypic diversity in bacterial chemotaxis. Next, we discuss the functional consequences of phenotypic diversity for the chemosensing and chemotactic performance of single cells and populations. Finally, we discuss mechanisms that modulate the amount of phenotypic diversity in chemosensory parameters in response to changes in the environment.
Zn-Enhanced Asp-Rich Antimicrobial Peptides: N-Terminal Coordination by Zn(II) and Cu(II), Which Distinguishes Cu(II) Binding to Different Peptides
Authors: Miller Adriana , Matera-Witkiewicz Agnieszka , Mikołajczyk Aleksandra , Wątły Joanna , Wilcox Dean , Witkowska Danuta , Rowińska-Żyrek Magdalena
Published: June 2021

The antimicrobial activity of surfactant-associated anionic peptides (SAAPs), which are isolated from the ovine pulmonary surfactant and are selective against the ovine pathogen Mannheimia haemolytica, is strongly enhanced in the presence of Zn(II) ions. Both calorimetry and ITC measurements show that the unique Asp-only peptide SAAP3 (DDDDDDD) and its analogs SAAP2 (GDDDDDD) and SAAP6 (GADDDDD) have a similar micromolar affinity for Zn(II), which binds to the N-terminal amine and Asp carboxylates in a net entropically-driven process. All three peptides also bind Cu(II) with a net entropically-driven process but with higher affinity than they bind Zn(II) and coordination that involves the N-terminal amine and deprotonated amides as the pH increases. The parent SAAP3 binds Cu(II) with the highest affinity; however, as shown with potentiometry and absorption, CD and EPR spectroscopy, Asp residues in the first and/or second positions distinguish Cu(II) binding to SAAP3 and SAAP2 from their binding to SAAP6, decreasing the Cu(II) Lewis acidity and suppressing its square planar amide coordination by two pH units. We also show that these metal ions do not stabilize a membrane disrupting ability nor do they induce the antimicrobial activity of these peptides against a panel of human pathogens.
On the Need to Tell Apart Fraternal Twins eEF1A1 and eEF1A2, and Their Respective Outfits
Authors: Mills Alberto , Gago Federico
Published: June 2021

eEF1A1 and eEF1A2 are paralogous proteins whose presence in most normal eukaryotic cells is mutually exclusive and developmentally regulated. Often described in the scientific literature under the collective name eEF1A, which stands for eukaryotic elongation factor 1A, their best known activity (in a monomeric, GTP-bound conformation) is to bind aminoacyl-tRNAs and deliver them to the A-site of the 80S ribosome. However, both eEF1A1 and eEF1A2 are endowed with multitasking abilities (sometimes performed by homo- and heterodimers) and can be located in different subcellular compartments, from the plasma membrane to the nucleus. Given the high sequence identity of these two sister proteins and the large number of post-translational modifications they can undergo, we are often confronted with the dilemma of discerning which is the particular proteoform that is actually responsible for the ascribed biochemical or cellular effects. We argue in this review that acquiring this knowledge is essential to help clarify, in molecular and structural terms, the mechanistic involvement of these two ancestral and abundant G proteins in a variety of fundamental cellular processes other than translation elongation. Of particular importance for this special issue is the fact that several de novo heterozygous missense mutations in the human EEF1A2 gene are associated with a subset of rare but severe neurological syndromes and cardiomyopathies.
A Role for Xanthurenic Acid in the Control of Brain Dopaminergic Activity
Authors: Taleb Omar , Maammar Mohammed , Klein Christian , Maitre Michel , Mensah-Nyagan Ayikoe Guy
Published: June 2021

Xanthurenic acid (XA) is a metabolite of the kynurenine pathway (KP) synthetized in the brain from dietary or microbial tryptophan that crosses the blood-brain barrier through carrier-mediated transport. XA and kynurenic acid (KYNA) are two structurally related compounds of KP occurring at micromolar concentrations in the CNS and suspected to modulate some pathophysiological mechanisms of neuropsychiatric and/or neurodegenerative diseases. Particularly, various data including XA cerebral distribution (from 1 µM in olfactory bulbs and cerebellum to 0.1–0.4 µM in A9 and A10), its release, and interactions with G protein-dependent XA-receptor, glutamate transporter and metabotropic receptors, strongly support a signaling and/or neuromodulatory role for XA. However, while the parent molecule KYNA is considered as potentially involved in neuropsychiatric disorders because of its inhibitory action on dopamine release in the striatum, the effect of XA on brain dopaminergic activity remains unknown. Here, we demonstrate that acute local/microdialysis-infusions of XA dose-dependently stimulate dopamine release in the rat prefrontal cortex (four-fold increase in the presence of 20 µM XA). This stimulatory effect is blocked by XA-receptor antagonist NCS-486. Interestingly, our results show that the peripheral/intraperitoneal administration of XA, which has been proven to enhance intra-cerebral XA concentrations (about 200% increase after 50 mg/kg XA i.p), also induces a dose-dependent increase of dopamine release in the cortex and striatum. Furthermore, our in vivo electrophysiological studies reveal that the repeated/daily administrations of XA reduce by 43% the number of spontaneously firing dopaminergic neurons in the ventral tegmental area. In the substantia nigra, XA treatment does not change the number of firing neurons. Altogether, our results suggest that XA may contribute together with KYNA to generate a KYNA/XA ratio that may crucially determine the brain normal dopaminergic activity. Imbalance of this ratio may result in dopaminergic dysfunctions related to several brain disorders, including psychotic diseases and drug dependence.
Identification of Fake Stereo Audio Using SVM and CNN
Authors: Liu Tianyun , Yan Diqun , Wang Rangding , Yan Nan , Chen Gang
Published: June 2021

The number of channels is one of the important criteria in regard to digital audio quality. Generally, stereo audio with two channels can provide better perceptual quality than mono audio. To seek illegal commercial benefit, one might convert a mono audio system to stereo with fake quality. Identifying stereo-faking audio is a lesser-investigated audio forensic issue. In this paper, a stereo faking corpus is first presented, which is created using the Haas effect technique. Two identification algorithms for fake stereo audio are proposed. One is based on Mel-frequency cepstral coefficient features and support vector machines. The other is based on a specially designed five-layer convolutional neural network. The experimental results on two datasets with five different cut-off frequencies show that the proposed algorithm can effectively detect stereo-faking audio and has good robustness.
Influence of Patching on the Shear Failure of Reinforced Concrete Beam without Stirrup
Authors: Kristiawan Stefanus Adi , Saifullah Halwan Alfisa , Supriyadi Agus
Published: June 2021

Deteriorated concrete cover, e.g., spalling or delamination, especially when it occurs at the web of a reinforced concrete (RC) beam within the shear span, can reduce the shear capacity of the beam. Patching of this deteriorated area may be the best option to recover the shear capacity of the beam affected. For this purpose, unsaturated polyester resin mortar (UPR mortar) has been formulated. This research aims to investigate the efficacy of UPR mortar in limiting the shear cracking and so restoring the shear capacity of the deteriorated RC beam. The investigation is carried out by an experimental and numerical study. Two types of beams with a size of 150 × 250 × 1000 mm were prepared. The first type of beams was assigned as a normal beam. The other was a beam with a cut off in the non-stirrup shear span, which was eventually patched with UPR mortar. Two reinforcement ratios were assigned for each type of beams. The results show that UPR mortar is effective to hamper the propagation of diagonal cracks leading to increase the shear failure load by 15–20% compared to the reference (normal) beam. The increase of shear strength with the use of UPR mortar is consistently confirmed at various reinforcement ratios.
Different Performance of Phthorimaea operculella Zeller (Lepidoptera: Gelechiidae) among Four Potato Tuber Varieties under Laboratory Condition
Authors: Zhang Mengdi , Yan Junjie , Ali Abid , Gao Yulin
Published: June 2021

The potato tuber moth Phthorimaea operculella Zeller is one of the most damaging potato pests in the world and is difficult to control as the larvae feed only inside potatoes. Evaluating the effects of performance of P. operculella on different potato varieties may help to facilitate the development of effective pest management practices. In our study, P. operculella reared on potato variety Lishu6 showed strong performance and on Qingshu 9 exhibited the poorest performance, while P. operculella fed on Hezuo 88 and Yunshu 304 performed moderately. Firstly, larval performance of P. operculella fed on Lishu 6 with that on Hezuo 88, Yunshu 304, and Qingshu 9 was compared by using an age-stage two-sex life table. Compared with larvae fed on Lishu 6, those fed on Qingshu 9 exhibited significantly lower survival, with only 5.56% developing to the adult stage. Secondly, the pupal weight experiment showed that the pupae weight of P. operculella feeding on Lishu 6 tubers (0.0123 g) was significantly heavier than that those feeding on Qingshu 9 (0.0102 g) (p < 0.001). Thirdly, female oviposition and larvae feeding preference indicated that females oviposited on Lishu 6 in preference to Qingshu 9 (p < 0.05, p < 0.001). Overall, this study demonstrated that Qingshu 9 is the least suitable host, and planting this variety over a large scale can provide a basis for the next step of P. operculella control.
Spatio-Temporal Analysis of Satellite Imagery (NDVI) to Identify Terroir and Vineyard Yeast Differences according to Appellation of Origin (AOP) and Biogeographic Origin
Authors: Vélez Sergio , Barajas Enrique , Blanco Pilar , Rubio José Antonio , Castrillo David
Published: June 2021

Terroir is one of the core concepts associated with wine and presumes that the land from which the grapes are grown, the plant habitat, imparts a unique quality that is specific to that growing site. Additionally, numerous factors can influence yeast diversity, and terroir is among the most relevant. Therefore, it can be interesting to use Remote Sensing tools that help identify and give helpful information about the terroir and key characteristics that define the AOP (Appellation of Origin). In this study, the NDVI (Normalized Difference Vegetation Index) calculated from Landsat 8 imagery was used to perform a spatio-temporal analysis during 2013, 2014, and 2015 of several vineyards belonging to four different AOP in Galicia (Spain). This work shows that it is possible to use Remote Sensing for AOP delimitation. Results suggest: (i) satellite imagery can establish differences in terroir, (ii) the higher the NDVI, the higher the yeast species richness, (iii) the relationship between NDVI, terroir, and yeasts shows a stable trend over the years (Pearson’s r = 0.3894, p = 0.0119).
Recurrence after Curative Resection for Intrahepatic Cholangiocarcinoma: How to Predict the Chance of Repeat Hepatectomy?
Authors: Langella Serena , Russolillo Nadia , Ossola Paolo , Luzzi Andrea-Pierre , Casella Michele , Lo Tesoriere Roberto , Ferrero Alessandro
Published: June 2021

(1) Background: Tumor recurrence after liver resection (LR) for intrahepatic cholangiocarcinoma (ICC) is common. Repeat liver resection (RLR) for recurrent ICC results in good survival outcomes in selected patients. The aim of this study was to investigate factors affecting the chance of resectability of recurrent ICC. (2) Methods: LR for ICC performed between January 2001 and December 2020 were retrospectively reviewed. Patients who had undergone first LR were considered for the study. Data on recurrences were analyzed. A logistic regression model was used for multivariable analysis of factors related to RLR rate. (3) Results: In total, 140 patients underwent LR for ICC. Major/extended hepatectomies were required in 105 (75%) cases. The 90-day mortality was 5.7%, Clavien–Dindo grade 3, 4 complications were 9.3%, N+ disease was observed in 32.5%, and the median OS was 38.3 months. Recurrence occurred in 91 patients (65%). The site of relapse was the liver in 53 patients (58.2%). RLR was performed in 21 (39.6%) patients. Factors that negatively affected RLR were time to recurrence ≤12 months (OR 7.4, 95% CI 1.68–33.16, p = 0.008) and major hepatectomy (OR 16.7, 95% CI 3.8–73.78, p < 0.001) at first treatment. Survival after recurrence was better in patients who underwent RLR as compared with not resected patients (31 vs. 13.2 months, p = 0.02). (4) Conclusions: Patients with ICC treated at first resection with major hepatectomy and those who recurred in ≤12 months had significantly lower probability to receive a second resection for recurrence.
Multiphoton Imaging of Ca2+ Instability in Acute Myocardial Slices from a RyR2R2474S Murine Model of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Borile Giulia , Zaglia Tania , E. Lehnart Stephan , Mongillo Marco
Published: June 2021

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a familial stress-induced arrhythmia syndrome, mostly caused by mutations in Ryanodine receptor 2 (RyR2), the sarcoplasmic reticulum (SR) Ca2+ release channel in cardiomyocytes. Pathogenetic mutations lead to gain of function in the channel, causing arrhythmias by promoting diastolic spontaneous Ca2+ release (SCR) from the SR and delayed afterdepolarizations. While the study of Ca2+ dynamics in single cells from murine CPVT models has increased our understanding of the disease pathogenesis, questions remain on the mechanisms triggering the lethal arrhythmias at tissue level. Here, we combined subcellular analysis of Ca2+ signals in isolated cardiomyocytes and in acute thick ventricular slices of RyR2R2474S knock-in mice, electrically paced at different rates (1–5 Hz), to identify arrhythmogenic Ca2+ dynamics, from the sub- to the multicellular perspective. In both models, RyR2R2474S cardiomyocytes had increased propensity to develop SCR upon adrenergic stimulation, which manifested, in the slices, with Ca2+ alternans and synchronous Ca2+ release events in neighboring cardiomyocytes. Analysis of Ca2+ dynamics in multiple cells in the tissue suggests that SCRs beget SCRs in contiguous cells, overcoming the protective electrotonic myocardial coupling, and potentially generating arrhythmia triggering foci. We suggest that intercellular interactions may underscore arrhythmic propensity in CPVT hearts with ‘leaky’ RyR2.
The Antihypertensive Effects and Safety of LCZ696 in Patients with Hypertension: A Systemic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Chua Su-Kiat , Lai Wei-Ting , Chen Lung-Ching , Hung Huei-Fong
Published: June 2021

Background: The management of hypertension remains suboptimal throughout the world. Methods: We performed a random-effects model meta-analysis of randomized controlled trials to determine the effectiveness and safety of sacubitril/valsartan (LCZ696) for the treatment of high arterial pressure. Relevant published articles from PubMed, Cochrane base, and Medline were examined, and the last search date was December 2020. Only published randomized controlled trials and double-blind studies were selected for further analysis. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position, as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events (AEs) were considered as safety outcomes. Results: Ten studies with a total of 5931patients were included for analysis. Compared with placebo, LCZ696 had a significant reduction in msSBP (weight mean difference (WMD) = −6.52 mmHg, 95% confidence interval (CI): −8.57 to −4.47; p < 0.001), msDBP (WMD = −3.32 mmHg, 95% CI: −4.57 to −2.07; p < 0.001), maSBP (WMD = −7.08 mmHg, 95% CI: −10.48 to −3.68; p < 0.001), maDBP (WMD = −3.57 mmHg, 95% CI: −5.71 to −1.44, p < 0.001). In subgroup analysis, only 200 mg and 400 mg LCZ696 showed a significant BP reduction. There was no difference in the AE rate between the LCZ696 and placebo groups (WMD = 1.02, 95% CI: 0.83 to 1.27, p = 0.54). Egger’s test revealed a potential publication bias for msSBP (p = 0.025), but no publication bias for other outcomes. Conclusion: LCZ696 may reduce blood pressure more efficaciously than traditional therapy in hypertensive patients without increasing adverse effects.
Echocardiography in Pulmonary Arterial Hypertension: Is It Time to Reconsider Its Prognostic Utility?
Authors: Farmakis Ioannis T. , Demerouti Eftychia , Karyofyllis Panagiotis , Karatasakis George , Stratinaki Maria , Tsiapras Dimitrios , Athanassopoulos George , Voudris Vassilios , Giannakoulas George
Published: June 2021

Pulmonary arterial hypertension (PAH) is characterized by an insult in the pulmonary vasculature, with subsequent right ventricular (RV) adaptation to the increased afterload that ultimately leads to RV failure. The awareness of the importance of RV function in PAH has increased considerably because right heart failure is the predominant cause of death in PAH patients. Given its wide availability and reduced cost, echocardiography is of paramount importance in the evaluation of the right heart in PAH. Several echocardiographic parameters have been shown to have prognostic implications in PAH; however, the role of echocardiography in the risk assessment of the PAH patient is limited under the current guidelines. This review discusses the echocardiographic evaluation of the RV in PAH and during therapy, and its prognostic implications, as well as the potential significant role of repeated echocardiographic assessment in the follow-up of patients with PAH.
Intranasal Dexmedetomidine Compared to a Combination of Intranasal Dexmedetomidine with Ketamine for Sedation of Children Requiring Dental Treatment: A Randomized Clinical Trial
Authors: Sado-Filho Joji , Corrêa-Faria Patrícia , Viana Karolline , Mendes Fausto , Mason Keira , Costa Luciane , Costa Paulo
Published: June 2021

Outpatient pediatric sedation is challenging. This study aimed to test intranasal dexmedetomidine efficacy as a single drug or combined with ketamine (DK) to sedate children undergoing dental treatment. Children < 7 years were randomized into dexmedetomidine 2 mcg/kg and ketamine 1 mg/kg (DK) or dexmedetomidine 2.5 mcg/kg (D) groups. Videos from the dental sedation allowed the systematic assessment of children’s behavior (primary outcome) according to the Ohio State University Behavioral Rating Scale (OSUBRS). Secondary outcomes were parental and dentist satisfaction, adverse events, and recovery time. The data were analyzed descriptively and through regression models. Participants were 88 children (44 per group; 50 boys). The duration of quiet behavior (OSUBRS) was higher than 50% (DK mean 58.4 [standard deviation 38.1]; D 55.2 [39.1]; p = 0.225). Parents (DK 78.0 [32.2]; D 72.7 [35.1]; p = 0.203) and dentists (KD 62.7 [41.0]; D 62.8 [40.1]; p = 0.339) were overall satisfied. Adverse events occurred in 16 cases (DK n = 10, 62.5%; D n= 6, 37.5%; p = 0.104) and were minor. The median recovery time in the DK group was 1.3 times greater than in group D (p < 0.05). Intranasal sedation with dexmedetomidine alone is equally efficacious and satisfactory for pediatric sedation with fewer adverse events and faster recovery than the DK combination.
Angioedema Coexisting Chronic Spontaneous Urticaria Negatively Influences Patients’ Sense of Coherence, What Results in Susceptibility to Anxiety Symptoms Occurrence
Authors: Badura-Brzoza Karina , Brzoza Zenon
Published: June 2021

Background: Angioedema coexisting chronic spontaneous urticaria (CSU) is proved to result in patient anxiety occurrence, but the mechanisms and susceptibility patterns are unknown. Sense of coherence (SOC) is one of methods of coping with stress and is defined as a person’s general orientation toward life. We decided to assess SOC disturbances in CSU patients in the context of possible angioedema association. Methods: The study comprised 71 CSU subjects. To analyze disease activity, the Urticaria Activity Score seven-day assessment questionnaire (UAS7) was used. For anxiety assessment, the STAI questionnaire was used. The SOC-29 questionnaire, consisting of questions related to comprehensibility (SOC-C), manageability (SOC-M), and meaningfulness (SOC-Mf), was used to analyze SOC parameters (SOC-T). Results: In patients with coexisting angioedema, we observed statistically significantly lower values of SOC-Mf and SOC-T in comparison to the wheals only group. In the angioedema group, we noticed significant negative correlations between SOC-M and SOC-Mf, as well as SOC-T values and anxiety. In the wheals only group, we proved statistically significant correlations between SOC-Mf and SOC-T and anxiety assessed as a state. Conclusions: It is necessary to identify CSU patients manifesting angioedema as they are more likely to have impaired SOC. Lower SOC in this specific group of patients can be related to anxiety symptoms occurrence and should probably be an indication for psychological support.
Simultaneous Hybrid Treatment of Multilevel Peripheral Arterial Disease in Patients with Chronic Limb-Threatening Ischemia
Authors: Pecoraro Felice , Pakeliani David , Bruno Salvatore , Dinoto Ettore , Ferlito Francesca , Mirabella Domenico , Lachat Mario , Cudia Bianca , Bajardi Guido
Published: June 2021

Background: Hybrid treatments (HT) aim to reduce conventional open surgery invasiveness and address multilevel peripheral arterial disease (PAD). Herein, the simultaneous HT treatment in patients with chronic limb-threatening ischemia (CLTI) is reported. Methods: Retrospective analysis, for the period from May 2012 to April 2018, of patients presenting multilevel PAD with CLTI addressed with simultaneous HT. The outcomes of these interventions were measured the following metrics: early technical successes (within 30 days following treatment) and late technical successes (30 days or more following treatment) and included mortality, morbidity symptoms recurrence, and amputation. Survival and patencies were estimated. The median follow-up was 43.77 months. Results: In the 45 included patients, the HT consisted of femoral bifurcation patch angioplasty followed by an endovascular treatment in 38 patients (84.4%) and endovascular treatment followed by a surgical bypass in 7 patients (15.6%). Technical success was 100% without perioperative mortality. Eight (17.8%) patients presented early complications without major amputations. During the follow-up, seven (15.6%) deaths occurred and six patients (13.3%) experienced symptoms recurrence, with five of those patients requiring major amputation. An estimated survival time of 5 years, primary patency, and secondary patency was 84.4%, 79.2%, and 83.3% respectively. Conclusions: Hybrid treatments are effective in addressing patients presenting with multilevel PAD and CLTI. The common femoral artery involvement influences strategy selection. Larger studies with longer-term outcomes are required to validate the hybrid approach, indications, and results.
The Clinical Effects of Steroids Therapy in the Preserving Residual Hearing after Cochlear Implantation with the OTICON Neuro Zti EVO
Authors: Skarzynska Magdalena B. , Kolodziejak Aleksandra , Gos Elżbieta , Skarzynski Piotr H.
Published: June 2021

Background: A prospective clinical study was conducted to investigate whether two different pharmacotherapy strategies of steroid administration impact hearing preservation in adult patients who underwent cochlear implantation with the Oticon Medical Neuro cochlear implant system. Methods: Twenty nine adult participants were included. Pure tone audiometry was performed before implantation, during processor activation and 12 months after activation. There were three treatment groups: (1) intravenous steroid therapy (standard steroid therapy with dexamethasone administrated intravenously at the dose 0.1 mg/kg body mass twice a day); (2) combined oral and intravenous steroid therapy (extended steroid therapy with dexamethasone administrated intravenously at the dose 0.1 mg/kg b.m. twice a day and prednisone (orally) at the dose 1 mg/kg body mass/24 h), and (3) no steroid therapy (a control group). Patients’ hearing thresholds before implantation were on average 103 dB HL, 89 dB HL, and 93 dB HL, respectively. Results: Deterioration of hearing thresholds was observed in all three patients’ groups. Twelve months after surgery the patients with and without steroid therapy had similar hearing thresholds. Conclusions: The steroid regimen used in this study did not play a significant role in patients with non-functional residual hearing, who underwent cochlear implantation with the Oticon Medical Neuro cochlear implant system.
MDSC in Mice and Men: Mechanisms of Immunosuppression in Cancer
Authors: Vanhaver Christophe , van der Bruggen Pierre , Bruger Annika M.
Published: June 2021

Myeloid-derived suppressor cells (MDSCs) expand during pathological conditions in both humans and mice and their presence is linked to poor clinical outcomes for cancer patients. Studying MDSC immunosuppression is restricted by MDSCs’ rarity, short lifespan, heterogeneity, poor viability after freezing and the lack of MDSC-specific markers. In this review, we will compare identification and isolation strategies for human and murine MDSCs. We will also assess what direct and indirect immunosuppressive mechanisms have been attributed to MDSCs. While some immunosuppressive mechanisms are well-documented in mice, e.g., generation of ROS, direct evidence is still lacking in humans. In future, bulk or single-cell genomics could elucidate which phenotypic and functional phenotypes MDSCs adopt in particular microenvironments and help to identify potential targets for therapy.
Hemodynamic Response, Coughing and Incidence of Cerebrospinal Fluid Leakage on Awakening with an Endotracheal Tube or Laryngeal Mask Airway in Place after Transsphenoidal Pituitary Surgery: A Randomized Clinical Trial
Authors: Hurtado Paola , Tercero Javier , Garcia-Orellana Marta , Enseñat Joaquim , Reyes Luis , Cabedo Gemma , Rios Jose , Carrero Enrique , de Riva Nicolas , Fontanals Jaume , Gracia Isabel , Belda Isabel , Lopez Ana M. , Fabregas Neus , Valero Ricard
Published: June 2021

We aimed to compare systemic and cerebral hemodynamics and coughing during emergence after pituitary surgery after endotracheal tube (ETT) extubation or after replacing ETT with a laryngeal mask airway (LMA). Patients were randomized to awaken with an ETT in place or after replacing it with an LMA. We recorded mean arterial pressure (MAP), heart rate, middle cerebral artery (MCA) flow velocity, regional cerebral oxygen saturation (SrO2), cardiac index, plasma norepinephrine, need for vasoactive drugs, coughing during emergence, and postoperative cerebrospinal fluid (CSF) leakage. The primary endpoint was postoperative MAP; secondary endpoints were SrO2 and coughing incidence. Forty-five patients were included. MAP was lower during emergence than at baseline in both groups. There were no significant between-group differences in blood pressure, nor in the number of patients that required antihypertensive drugs during emergence (ETT: 8 patients (34.8%) vs. LMA: 3 patients (14.3%); p = 0.116). MCA flow velocity was higher in the ETT group (e.g., mean (95% CI) at 15 min, 103.2 (96.3–110.1) vs. 89.6 (82.6–96.5) cm·s−1; p = 0.003). SrO2, cardiac index, and norepinephrine levels were similar. Coughing was more frequent in the ETT group (81% vs. 15%; p < 0.001). CSF leakage occurred in three patients (13%) in the ETT group. Placing an LMA before removing an ETT during emergence after pituitary surgery favors a safer cerebral hemodynamic profile and reduces coughing. This strategy may lower the risk for CSF leakage.
Impact of Membrane Lipids on UapA and AzgA Transporter Subcellular Localization and Activity in Aspergillus nidulans
Authors: Dionysopoulou Mariangela , Diallinas George
Published: June 2021

Recent biochemical and biophysical evidence have established that membrane lipids, namely phospholipids, sphingolipids and sterols, are critical for the function of eukaryotic plasma membrane transporters. Here, we study the effect of selected membrane lipid biosynthesis mutations and of the ergosterol-related antifungal itraconazole on the subcellular localization, stability and transport kinetics of two well-studied purine transporters, UapA and AzgA, in Aspergillus nidulans. We show that genetic reduction in biosynthesis of ergosterol, sphingolipids or phosphoinositides arrest A. nidulans growth after germling formation, but solely blocks in early steps of ergosterol (Erg11) or sphingolipid (BasA) synthesis have a negative effect on plasma membrane (PM) localization and stability of transporters before growth arrest. Surprisingly, the fraction of UapA or AzgA that reaches the PM in lipid biosynthesis mutants is shown to conserve normal apparent transport kinetics. We further show that turnover of UapA, which is the transporter mostly sensitive to membrane lipid content modification, occurs during its trafficking and by enhanced endocytosis, and is partly dependent on autophagy and Hect-type HulARsp5 ubiquitination. Our results point out that the role of specific membrane lipids on transporter biogenesis and function in vivo is complex, combinatorial and transporter-dependent.
Nitrogen, Iron, and Zinc Acquisition: Key Nutrients to Aspergillus fumigatus Virulence
Authors: Perez-Cuesta Uxue , Guruceaga Xabier , Cendon-Sanchez Saioa , Pelegri-Martinez Eduardo , Hernando Fernando L. , Ramirez-Garcia Andoni , Abad-Diaz-de-Cerio Ana , Rementeria Aitor
Published: June 2021

Aspergillus fumigatus is a ubiquitous soil decomposer and an opportunistic pathogen that is characterized by its large metabolic machinery for acquiring nutrients from media. Lately, an ever-increasing number of genes involved in fungal nutrition has been associated with its virulence. Of these, nitrogen, iron, and zinc metabolism-related genes are particularly noteworthy, since 78% of them have a direct implication in virulence. In this review, we describe the sensing, uptake and regulation process of the acquisition of these nutrients, the connections between pathways and the virulence-implicated genes. Nevertheless, only 40% of the genes mentioned in this review have been assayed for roles in virulence, leaving a wide field of knowledge that remains uncertain and might offer new therapeutic and diagnostic targets.
Schizophrenia-Like Behavioral Impairments in Mice with Suppressed Expression of Piccolo in the Medial Prefrontal Cortex
Authors: Nitta Atsumi , Izuo Naotaka , Hamatani Kohei , Inagaki Ryo , Kusui Yuka , Fu Kequan , Asano Takashi , Torii Youta , Habuchi Chikako , Sekiguchi Hirotaka , Iritani Shuji , Muramatsu Shin-ichi , Ozaki Norio , Miyamoto Yoshiaki
Published: June 2021

Piccolo, a presynaptic cytomatrix protein, plays a role in synaptic vesicle trafficking in the presynaptic active zone. Certain single-nucleotide polymorphisms of the Piccolo-encoding gene PCLO are reported to be associated with mental disorders. However, a few studies have evaluated the relationship between Piccolo dysfunction and psychotic symptoms. Therefore, we investigated the neurophysiological and behavioral phenotypes in mice with Piccolo suppression in the medial prefrontal cortex (mPFC). Downregulation of Piccolo in the mPFC reduced regional synaptic proteins, accompanied with electrophysiological impairments. The Piccolo-suppressed mice showed an enhanced locomotor activity, impaired auditory prepulse inhibition, and cognitive dysfunction. These abnormal behaviors were partially ameliorated by the antipsychotic drug risperidone. Piccolo-suppressed mice received mild social defeat stress showed additional behavioral despair. Furthermore, the responses of these mice to extracellular glutamate and dopamine levels induced by the optical activation of mPFC projection in the dorsal striatum (dSTR) were inhibited. Similarly, the Piccolo-suppressed mice showed decreased depolarization-evoked glutamate and -aminobutyric acid elevations and increased depolarization-evoked dopamine elevation in the dSTR. These suggest that Piccolo regulates neurotransmission at the synaptic terminal of the projection site. Reduced neuronal connectivity in the mPFC-dSTR pathway via suppression of Piccolo in the mPFC may induce behavioral impairments observed in schizophrenia.
Impact of Land Use Changes on the Erosion Processes of a Degraded Rural Landscape: An Analysis Based on High-Resolution DEMs, Historical Images, and Soil Erosion Models
Authors: Gioia Dario , Minervino Amodio Antonio , Maggio Agata , Sabia Canio Alfieri
Published: June 2021

Soil erosion is one of the major natural risk factors for developing high-value crops and an accurate estimation of spatial distribution and rates of soil degradation can be crucial to prevent crop degradation. In this paper, we use comparisons between high-resolution DEMs and soil erosion models to uncover the short-term landscape evolution of hazelnut crop yields, which are affected by incipient processes of rill development. Maps of rill initiation and evolution were extracted from the analysis of UAV-based multitemporal DEMs and the application of soil erosion models. A comparison between such a short-term analysis and historical orthophotos was carried out. Such a comparison shows how the USPED model predicts, very reliably, where linear erosion occurred. In fact, a reliable overlay between the linear erosive forms predicted by the USPED model and those captured by the UAV images can be observed. Furthermore, land use changes from 1974 to 2020 are characterized by a transition from abandoned areas (1974) to areas with high-value cultivation (2020), which has a strong impact on the spatial distribution of erosion processes and landslide occurrence. Such data represent a key tool for both the investigation of the spatial distribution of hot-spots of soil degradation and the identification of effective mitigation practices of soil conservation.
Co-Management of Protected Areas: A Governance System Analysis of Vatnajökull National Park, Iceland
Authors: Petursson Jon Geir , Kristofersson Dadi Mar
Published: June 2021

Land allocated to protected areas (PA) is expanding as are expectations about the services these areas deliver. There is a need to advance knowledge on PA governance systems, like co-management, recognising that there is no “one-size-fits-all” solution. We analyse the co-management governance system and performance of Vatnajökull National Park (VNP), Iceland. We adapt an analytical framework from the literature on environmental governance and analyse its governance system, hence actor roles, institutional arrangements and interactions. Our findings illustrate that the co-management structure was an outcome of political negotiations and a response to the lack of legitimacy of its predecessors; resulting in a tailor-made governance system set out in park-specific legislation. Although the performance is quite positive, being adaptive to changes, inclusive, promoting rural development and an appreciated facilitator of devolution and power-sharing, it has come with challenges. It has encountered problems delineating responsibilities among its actors, causing conflict and confusion; in settling conflicting localised issues close to local stakeholders, there have been capacity issues. We argue that the VNP co-management system is fit for its purpose, aligned with Icelandic land-use governance structures but in need of systematic improvements. There are important lessons as Iceland seeks to expand its PA estate and beyond, since the global community is setting ambitious policy goals to expand site-based conservation.
A Simple GIS-Based Tool for the Detection of Landslide-Prone Zones on a Coastal Slope in Scotland
Authors: Gonzalez-Ollauri Alejandro , Mickovski Slobodan B.
Published: June 2021

Effective landslide detection is crucial to mitigate the negative impacts derived from the occurrence of these natural hazards. Research on landslide detection methods has been extensively undertaken. However, simplified methods for landslide detection requiring a minimum amount of data inputs are still lacking. Simple approaches for landslide detection should be particularly interesting for geographical areas with limited information or resources availability. The aim of this paper is to present a refined, simple, GIS-based tool for the detection of landslide-prone and slope restoration zones. The tool only requires a digital elevation model (DEM) dataset as input, it is interoperable at multiple spatial scales, and it can be implemented on any GIS platform. The tool was applied on a coastal slope prone to instability, located in Scotland, in order to verify the functionality of the tool. The results indicated that the proposed tool is able to detect both shallow and deeper landslides satisfactorily, suggesting that the spatial combination of steep and potentially wet soil zones is effective for detecting areas prone to slope failure.