bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ageing of the somatosensory system at the periphery: age‐related changes in cutaneous mechanoreceptors
Authors: García‐Piqueras Jorge , García‐Mesa Yolanda , Cárcaba Lucia , Feito Jorge , Torres‐Parejo Isidro , Martín‐Biedma Benjamín , Cobo Juan , García‐Suárez Olivia , Vega Jose A. 
Published: March 2019

AbstractDecline of tactile sensation associated with ageing depends on modifications in skin and both central and peripheral nervous systems. At present, age‐related changes in the periphery of the somatosensory system, particularly concerning the effects on mechanoreceptors, remain unknown. Here we used immunohistochemistry to analyse the age‐dependent changes in Meissner's and Pacinian corpuscles as well as in Merkel cell‐neurite complexes. Moreover, variations in the neurotrophic TrkB‐BDNF system and the mechanoprotein Piezo2 (involved in maintenance of cutaneous mechanoreceptors and light touch, respectively) were evaluated. The number of Meissner's corpuscles and Merkel cells decreased progressively with ageing. Meissner's corpuscles were smaller, rounded in morphology and located deeper in the dermis, and signs of corpuscular denervation were found in the oldest subjects. Pacinian corpuscles generally showed no relevant age‐related alterations. Reduced expression of Piezo2 in the axon of Meissner's corpuscles and in Merkel cells was observed in old subjects, as well was a decline in the BDNF‐TrkB neurotrophic system. This study demonstrates that cutaneous Meissner's corpuscles and Merkel cell‐neurite complexes (and less evidently Pacinian corpuscles) undergo morphological and size changes during the ageing process, as well as a reduction in terms of density. Furthermore, the mechanoprotein Piezo2 and the neurotrophic TrkB‐BDNF system are reduced in aged corpuscles. Taken together, these alterations might explain part of the impairment of the somatosensory system associated with ageing.
A case of latanoprost‐induced diffuse facial skin hyperpigmentation
Authors: Kim Ho Young , Lee Soo Kyung , Lee Jae Ho , Suh Joong Heon , Kim Myoung Shin , Lee Un Ha 
Published: March 2019

SummaryIntroductionLatanoprost is a prostaglandin F2α analogue, which has been used as a first‐line drug for open‐angle glaucoma. Common side effects of latanoprost include hyperpigmentation. While it usually occurs on irides or periocular skin, diffuse facial hyperpigmentation is rarely reported.Case presentationA 71‐year‐old woman was presented with diffuse gray‐brown colored maculopatches on her face. The symptom appeared 1 week after she started to use latanoprost eye drops for glaucoma. Biopsy specimen revealed vacuolar degeneration of dermo‐epidermal junction and pigment incontinence in dermis.ObjectiveThe aim of this paper is to introduce a rare adverse effect of latanoprost and effective way of treatment.MethodsWe stopped her from using latanoprost. She was also treated with 532‐nm potassium titanyl phosphate laser and low‐fluence 1064‐nm Q‐switched Nd:YAG laser, while using topical agents.ResultAfter 10 weeks, we observed hyperpigmentation of her face was effectively and safely treated. The patient was satisfied with the result.ConclusionDiffuse facial pigmentation could be one of the latanoprost‐induced adverse effects and the laser treatments with topical agents we used can make it improve faster.
755 nm picosecond laser for facial atrophic scar—Case reports of long‐term clinical efficacy following up
Authors: Huang Ching‐Hsin , Hsieh Fu‐Sen , Chang Hung‐Chia , Peng Jui‐Hui , Peng Hsien‐Li Peter 
Published: March 2019

AbstractIntroductionAcne vulgaris is one of the most common dermatological problems in Asia. While the disease itself is self‐limited and temporary, the dystrophic texture changes after the inflammatory process are often a serious aesthetic concern. Many energy‐based devices have seen good results in treating atrophic acne scars, and the picosecond laser with specific lens is one of the newer options, and lack reports on its long‐term efficacy.Materials and MethodsWe report three Taiwanese cases who, to our knowledge, consist of the longest clinical follow‐up times for atrophic scar treatment with the 755 nm diffractive lens picosecond laser. Photographs were compared on a by‐session basis by two blinded dermatologists independent of the primary treating physician and given an improvement range of <25%, 25%‐50%, 50%‐75%, and >75%.ResultsWhile there are minor (<25%) improvements in all cases after the first four treatment sessions, all three cases saw the greatest improvement in skin texture (>75% in two cases, 50%‐75% in one) when they were followed up 6, 13.5, and 28 months post‐last treatment.ConclusionOur results demonstrate excellent, long‐onset, and long‐term efficacy of the picosecond laser with diffractive lens in the treatment of acne atrophic scars. It also demonstrates the safe use of the device on Asian skins without symptoms of postinflammatory hyperpigmentation.
Serious complication as a result of lip augmentation with vitamin E
Authors: Ehsani Amir Hooshang , Ansari Mahshid Sadat , Ghanadan Alireza , Mehdizade Rayeni Neda , Noormohammad Poor Pedram , Ansari Mahsa 
Published: March 2019

SummaryNowadays lip augmentation with FDA‐approved fillers is becoming popular. However, because of financial concerns many patients seek for unregistered materials. Here, we report two cases who use vitamin E for lip augmentation. They experience severe infiltration and discharge less than one month after injection. Biopsy revealed lipogranuloma formation. They were treated with incision and drainage, antibiotic, and corticosteroids. Although these complications are usually difficult to treat, the patients had good clinical response and no recurrence in 5‐month follow‐up.
H3K4 trimethylation by CclA regulates pathogenicity and the production of three families of terpenoid secondary metabolites in Colletotrichum higginsianum
Authors: Dallery Jean‐Félix , Adelin Émilie , Le Goff Géraldine , Pigné Sandrine , Auger Annie , Ouazzani Jamal , O'Connell Richard J. 
Published: March 2019

SummaryThe role of histone 3 lysine 4 (H3K4) methylation is poorly understood in plant pathogenic fungi. Here, we analysed the function of CclA, a subunit of the COMPASS complex mediating H3K4 methylation, in the brassica anthracnose pathogen Colletotrichum higginsianum. We show that CclA is required for full genome‐wide H3K4 trimethylation. The deletion of cclA strongly reduced mycelial growth, asexual sporulation and spore germination but did not impair the morphogenesis of specialized infection structures (appressoria and biotrophic hyphae). Virulence of the ΔcclA mutant on plants was strongly attenuated, associated with a marked reduction in appressorial penetration ability on both plants and inert cellophane membranes. The secondary metabolite profile of the ΔcclA mutant was greatly enriched compared to that of the wild type, with three different families of terpenoid compounds being overproduced by the mutant, namely the colletochlorins, higginsianins and sclerosporide. These included five novel molecules that were produced exclusively by the ΔcclA mutant: colletorin D, colletorin D acid, higginsianin C, 13‐epi‐higginsianin C and sclerosporide. Taken together, our findings indicate that H3K4 trimethylation plays a critical role in regulating fungal growth, development, pathogenicity and secondary metabolism in C. higginsianum.
Temporary heat stress suppresses PAMP‐triggered immunity and resistance to bacteria in Arabidopsis thaliana
Authors: Janda Martin , Lamparová Lucie , Zubíková Alžběta , Burketová Lenka , Martinec Jan , Krčková Zuzana 
Published: March 2019

SummaryRecognition of pathogen‐associated molecular patterns (PAMPs) is crucial for plant defence against pathogen attack. The best characterized PAMP is flg22, a 22 amino acid conserved peptide from flagellin protein. In Arabidopsis thaliana, flg22 is recognized by the flagellin sensing 2 (FLS2) receptor. In this study, we focused on biotic stress responses triggered by flg22 after exposure to temporary heat stress (HS). It is important to study the reactions of plants to multiple stress conditions because plants are often exposed simultaneously to a combination of both abiotic and biotic stresses. Transient early production of reactive oxygen species (ROS) is a well‐characterized response to PAMP recognition. We demonstrate the strong reduction of flg22‐induced ROS production in A. thaliana after HS treatment. In addition, a decrease in FLS2 transcription and a decrease of the FLS2 presence at the plasma membrane are shown after HS. In summary, our data show the strong inhibitory effect of HS on flg22‐triggered events in A. thaliana. Subsequently, temporary HS strongly decreases the resistance of A. thaliana to Pseudomonas syringae. We propose that short exposure to high temperature is a crucial abiotic stress factor that suppresses PAMP‐triggered immunity, which subsequently leads to the higher susceptibility of plants to pathogens.
Involvement of glutathione metabolism in Eichhornia crassipes tolerance to arsenic
Authors: de Souza Reis I. N. R , Alves de Oliveira J. , Ventrella M. C. , Otoni W. C. , Marinato C. S. , Paiva de Matos L. 
Published: March 2019

Abstract

Aquatic macrophytes are potentially useful for phytoremediation programmes in environments contaminated by arsenic (As). Biochemical and physiological modification analyses in different plant parts are important to understand As tolerance mechanisms.

The objective was to evaluate glutathione metabolism in leaves and roots of Eichhornia crassipes (Mart.) Solms treated to As. Specimens of E. crassipes were cultured for 3 days in Clark's nutrient solution containing 7 μm As. The enzymes ATP sulphurylase (ATPS), glutathione reductase (GR), glutathione peroxidase (GSH‐Px), glutathione sulphotransferase (GST) and γ‐glutamylcysteine synthetase (γ‐ECS) activity, glutathione content, total protein and non‐protein thiols were evaluated.

The ATPS activity increased in roots. GR activity in leaves and GSH‐Px in roots were lower. GST activity was higher in roots and lower in leaves, and γ‐ECS activity was higher in leaves. Glutathione levels were lower, total thiol levels were higher and non‐protein levels did not change in E. crassipes leaves and roots. Exposure to As increased enzyme activity involved with sulphur metabolism, such as ATPS. Higher GR activity and lower GSH‐Px indicate increased glutathione conjugation to As due to increased GSH availability. The higher GST activity indicates its participation in As detoxification and accumulation through As GSH conjugation. Changes in glutathione and thiol levels suggest high phytochelatin synthesis.

In conclusion, the increments in ATPS, GR, GST and γ‐ECS activity indicate that these enzymes are involved in GSH metabolism and are part of the E. crassipes As detoxification mechanism.
New insights into the distribution of alien cyanobacterium Chrysosporum bergii (Nostocales, Cyanobacteria)
Authors: Kokociński Mikołaj , Soininen Janne 
Published: March 2019

SUMMARYInvasive and alien cyanobacteria are considered as a serious threat to aquatic ecosystems due to their ability to produce cyanotoxins and outcompeting native species. Among cyanobacteria, Nostocales is a group with strong competitive advantages including the production of resting cells, ability to fix nitrogen or high affinity to phosphorus. A species Chrysosporum bergii has broadened its original distribution from brackish and seawater habitats of Caspian and Aral Seas to northern regions of Europe. The aim of our study was to expand the knowledge on the distribution of C. bergii, its preferred habitats in the invaded areas and examine whether the biomass of C. bergii is related with biomass of other alien or native cyanobacteria. We examined the phytoplankton community composition and the abiotic factors in randomly selected lakes of western Poland. For the first time, we showed that it occurs widely in lakes of this region. However, it occurred in one third of the investigated lakes and its contribution to total phytoplankton biomass was low. It occurred more frequently in shallow lakes with low conductivity and dissolved phosphorus, yet with higher total phosphorus concentration. The most remarkable finding was a negative relationship of C. bergii biomass with the biomass of native A. gracile, but a positive relationship with an invasive cyanobacterium C. raciborskii. This result suggests that these alien species occur under similar environmental conditions in Polish lakes. Moreover, the morphological features of C. bergii in Poland were similar to those of Anabaena bergii var. limnetica Couté et Preisig from Lithuania and Anabaena bergii from Czech Republic.
Shade delays flowering in Medicago sativa
Authors: Lorenzo Christian D. , Alonso Iserte Javier , Sanchez Lamas Maximiliano , Antonietti Mariana Sofia , Garcia Gagliardi Pedro , Hernando Carlos E. , Dezar Carlos Alberto A. , Vazquez Martin , Casal Jorge J. , Yanovsky Marcelo J. , Cerdán Pablo D. 
Published: March 2019

SummaryShade‐intolerant plants respond to the decrease in the red (R) to far‐red (FR) light ratio (R:FR) occurring under shade by elongating stems and petioles and by re‐positioning leaves, in a race to outcompete neighbors for the sunlight resource. In some annual species, the shade avoidance syndrome (SAS) is accompanied by the early induction of flowering. Anticipated flowering is viewed as a strategy to set seeds before the resources become severely limiting. Little is known about the molecular mechanisms of SAS in perennial forage crops like alfalfa (Medicago sativa). To study SAS in alfalfa, we exposed alfalfa plants to simulated shade by supplementing with FR light. Low R:FR light produced a classical SAS, with increased internode and petiole lengths, but unexpectedly also with delayed flowering. To understand the molecular mechanisms involved in uncoupling SAS from early flowering, we used a transcriptomic approach. The SAS is likely to be mediated by increased expression of msPIF3 and msHB2 in low R:FR light. Constitutive expression of these genes in Arabidopsis led to SAS, including early flowering, strongly suggesting that their roles are conserved. Delayed flowering was likely to be mediated by the downregulation of msSPL3, which promotes flowering in both Arabidopsis and alfalfa. Shade‐delayed flowering in alfalfa may be important to extend the vegetative phase under suboptimal light conditions, and thus assure the accumulation of reserves necessary to resume growth after the next season.
Can furosemide prevent transfusion‐associated circulatory overload? Results of a pilot, double‐blind, randomized controlled trial
Authors: Pendergrast Jacob , Armali Chantal , Cserti‐Gazdewich Christine , Hansen Mark , Kiss Alex , Lieberman Lani , Parmar Nagina , Scales Damon , Skeate Robert , Callum Jeannie , Lin Yulia 
Published: March 2019

BACKGROUNDTransfusion‐associated circulatory overload (TACO) is a leading cause of transfusion‐attributable morbidity. It is unclear whether diuretics are safe and effective in preventing this reaction.MATERIALS AND METHODSIn a pilot controlled feasibility trial, inpatients 65 years or older ordered a single unit of red blood cells were randomized to pre‐transfusion furosemide 20 mg or placebo intravenously. Primary outcome was the ability to enroll 80 patients within a 2‐month time period. Secondary feasibility outcomes included proportion of RBC transfusions meeting eligibility criteria, proportion of eligible patients enrolled, and compliance to study protocol. Clinical outcomes included the incidence of TACO and associated complications.RESULTSNine months of enrollment were required for 80 patients to complete the study, due primarily to fewer transfusions than expected meeting eligibility criteria and lower than anticipated consent rates. Protocol compliance was below target due to missing chart documentation of patient fluid balance, and transfusion infusion time. Blinding was maintained throughout the study and treatment arms were well‐balanced. A single case of TACO occurred in each arm, for an overall incidence of 2.5%. No differences in peri‐transfusion vital signs, B‐natriuretic peptide, or signs of furosemide toxicity were observed.CONCLUSIONThe study protocol was not feasible as designed, primarily due to challenges in patient enrollment. Modifications to trial design to improve feasibility in future studies have been identified.
Peripheral localization of the epithelial sodium channel in the apical membrane of bronchial epithelial cells
Authors: Musante Ilaria , Scudieri Paolo , Venturini Arianna , Guidone Daniela , Caci Emanuela , Castellani Stefano , Conese Massimo , Galietta Luis J.V. 
Published: March 2019

New Findings
What is the central question of this study?
What is the precise subcellular localization of the epithelial sodium channel (ENaC) in human airway epithelium?

What is the main finding and its importance?
ENaC protein has an unexpected localization in the peripheral region of the apical membrane of bronchial epithelial cells, very close to tight junctions. This may be important for the mechanism of Na+ absorption

AbstractThe epithelial sodium channel (ENaC) has a key role in absorbing fluid across the human airway epithelium. Altered activity of ENaC may perturb the process of mucociliary clearance, thus impairing the innate defence mechanisms against microbial agents. The proteins forming ENaC are present on the apical membrane of the epithelium. However, their precise localization is unknown. In the present study, we used two antibodies recognizing the α and β ENaC subunits. Both antibodies revealed a restricted localization of ENaC in the peripheral region of the apical membrane of cultured bronchial epithelial cells, close to but not overlapping with tight junctions. In contrast, the cystic fibrosis transmembrane conductance regulator chloride channel was more diffusely expressed on the whole apical membrane. Modulation of ENaC activity by aprotinin or elastase resulted in a decrease or increase in the peripheral localization, respectively. Our results suggest that sodium absorption is mainly occurring close to tight junctions where this cation may be rapidly expelled by the Na+/K+ pump present in lateral membranes. This arrangement of channels and pumps may limit Na+ build‐up in other regions of the cells.
Sildenafil does not reliably improve exercise performance in hypoxia: a systematic review
Authors: Carter Eric Alexander , Lohse Keith , Sheel William , Koehle Michael 
Published: March 2019

ObjectiveSildenafil is a pulmonary vasodilator that may reduce the decrement in endurance performance in moderate hypoxia. We assessed the efficacy of sildenafil to improve performance in hypoxia.Data sources/eligibility CriteriaWe systematically searched electronic databases (until August 2018) for randomised trials comparing sildenafil with placebo. We also examined the effect of sildenafil on pulmonary artery pressure (PAP), cardiac output (CO) and pulse oxygen saturation (SPO2) compared with placebo in hypoxia. Fourteen studies were included; 210 subjects received sildenafil 40, 50 or 100 mg/day.ResultsSildenafil showed a large effect for decreasing PAP during exercise and at rest, a small effect for increasing CO during exercise and a moderate effect at rest, a moderate effect for increasing SPO2and a small effect for improving performance. In a subgroup analysis, there was no statistically significant difference between 100 and 50 mg sildenafil dose on SPO2. Sildenafil had a moderate effect on increasing SPO2and performance at terrestrial hypobaric altitude but only a small effect on both in normobaric hypoxia. Regression analysis showed that hypoxic dose (PO2) and metabolic rate do not account for a significant portion of the variance in effect size for sildenafil on PAP, CO, SPO2and performance.ConclusionThis meta-analysis indicates that sildenafil reduces PAP, has a moderate to small effect on CO and SPO2, and no effect on performance.
Functional Analysis of Somatic Mutations Affecting Receptor Tyrosine Kinase Family in Metastatic Colorectal Cancer
Authors: Duplaquet Leslie , Figeac Martin , Leprêtre Frédéric , Frandemiche Charline , Villenet Céline , Sebda Shéhérazade , Sarafan-Vasseur Nasrin , Bénozène Mélanie , Vinchent Audrey , Goormachtigh Gautier , Wicquart Laurence , Rousseau Nathalie , Beaussire Ludivine , Truant Stéphanie , Michel Pierre , Sabourin Jean-Christophe , Galateau-Sallé Françoise , Copin Marie-Christine , Zalcman Gérard , De Launoit Yvan , Fafeur Véronique , Tulasne David 
Published: March 2019

Abstract
Besides the detection of somatic receptor tyrosine kinases (RTK) mutations in tumor samples, the current challenge is to interpret their biological relevance to give patients effective targeted treatment. By high-throughput sequencing of the 58 RTK exons of healthy tissues, colorectal tumors, and hepatic metastases from 30 patients, 38 different somatic mutations in RTKs were identified. The mutations in the kinase domains and present in both tumors and metastases were reconstituted to perform an unbiased functional study. Among eight variants found in seven RTKs (EPHA4-Met726Ile, EPHB2-Val621Ile, ERBB4-Thr731Met, FGFR4-Ala585Thr, VEGFR3-Leu1014Phe, KIT-Pro875Leu, TRKB-Leu584Val, and NTRK2-Lys618Thr), none displayed significantly increased tyrosine kinase activity. Consistently, none of them induced transformation of NIH3T3 fibroblasts. On the contrary, two RTK variants (FGFR4-Ala585Thr and FLT4-Leu1014Phe) caused drastic inhibition of their kinase activity. These findings indicate that these RTK variants are not suitable targets and highlight the importance of functional studies to validate RTK mutations as potential therapeutic targets.
Enhancing Therapeutic Efficacy of Oncolytic Herpes Simplex Virus-1 with Integrin β1 Blocking Antibody OS2966
Authors: Lee Tae Jin , Nair Mitra , Banasavadi-Siddegowda Yeshavanth , Liu Joseph , Nallanagulagari Tejaswini , Jaime-Ramirez Alena Cristina , Guo Jeffrey Yunhua , Quadri Haroon , Zhang Jianying , Bockhorst Kurt H. , Aghi Manish K. , Carbonell W. Shawn , Kaur Balveen , Yoo Ji Young 
Published: March 2019

Abstract
Integrin β1 receptor, expressed on the surface of tumor cells and macrophages in the tumor microenvironment (TME), has been implicated in both tumor progression and resistance to multiple modalities of therapy. OS2966 is the first clinical-ready humanized monoclonal antibody to block integrin β1 and was recently orphan designated by the FDA Office of Orphan Products Development. Here, we tested therapeutic potential of OS2966-mediated integrin β1 blockade to enhance the efficacy of oncolytic herpes simplex virus-1 (oHSV) through evaluation of virus replication, tumor cell killing efficiency, effect on the antiviral signaling pathway, co-culture assays of oHSV-infected cells with macrophages, and in vivo bioluminescence imaging on mammary fat pad triple-negative breast cancer xenograft and subcutaneous and intracranial glioma xenografts. OS2966 treatment decreased interferon signaling and proinflammatory cytokine induction in oHSV-treated tumor cells and inhibited migration of macrophages, resulting in enhanced oHSV replication and cytotoxicity. OS2966 treatment also significantly enhanced oHSV replication and oHSV-mediated antitumor efficacy in orthotopic xenograft models, including triple-negative breast cancer and glioblastoma. The results demonstrated the synergistic potential of the combinatory treatment approach with OS2966 to improve antitumor efficacy of conventional oHSV therapy.