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1.
Int J Audiol ; 62(10): 946-954, 2023 10.
Article En | MEDLINE | ID: mdl-36047767

OBJECTIVE: In daily life, failure to perceive emotional expressions can result in maladjusted behaviour. For cochlear implant users, perceiving emotional cues in sounds remains challenging, and the factors explaining the variability in patients' sensitivity to emotions are currently poorly understood. Understanding how these factors relate to auditory proficiency is a major challenge of cochlear implant research and is critical in addressing patients' limitations. DESIGN: To fill this gap, we evaluated different auditory perception aspects in implant users (pitch discrimination, music processing and speech intelligibility) and correlated them to their performance in an emotion recognition task. STUDY SAMPLE: Eighty-four adults (18-76 years old) participated in our investigation; 42 cochlear implant users and 42 controls. Cochlear implant users performed worse than their controls on all tasks, and emotion perception abilities were correlated to their age and their clinical outcome as measured in the speech intelligibility task. RESULTS: As previously observed, emotion perception abilities declined with age (here by about 2-3% in a decade). Interestingly, even when emotional stimuli were musical, CI users' skills relied more on processes underlying speech intelligibility. CONCLUSIONS: These results suggest that speech processing remains a clinical priority even when one is interested in affective skills.


Cochlear Implantation , Cochlear Implants , Deafness , Music , Speech Perception , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , Deafness/rehabilitation , Auditory Perception , Emotions , Speech Intelligibility , Pitch Perception
2.
Carbohydr Polym ; 251: 117027, 2021 Jan 01.
Article En | MEDLINE | ID: mdl-33142586

The direct dissolution and joint spinning of cellulose and lignin from NMMO-water were investigated by using dissolving pulp and purified KRAFT lignin. Compared to the rather narrow dissolution window of cellulose in the NMMO-water system, lignin with concentrations up to 15 wt.-% was shown to dissolve in a range from 30 % NMMO to 70 % NMMO at room temperature. The quasi-ternary phase diagram of cellulose-lignin-(NMMO-monohydrate) is represented by a cross section at 95 °C. Dry-jet wet spinning was realized for the cellulose-lignin compound up to 50 % lignin loading. The spinnability decreases with increasing lignin content. SEM and TEM investigations of the fibers exhibit a core-shell structure with a dense core and a porous shell with lower lignin content. In accordance with the X-ray fiber diagrams, it can be concluded that cellulose governs fiber formation and fiber properties while lignin acts mainly as a filler in the core region.

3.
AJNR Am J Neuroradiol ; 41(12): 2327-2332, 2020 12.
Article En | MEDLINE | ID: mdl-33122203

BACKGROUND AND PURPOSE: Imaging is essential in the diagnostic work-up of patients with orbital lesions. The position of an orbital lesion relative to the inferomedial muscular trunk of the ophthalmic artery determines endoscopic resectability, anticipated technical difficulty, and patient morbidity. Although the inferomedial muscular trunk is not readily identifiable on preoperative imaging, we hypothesize that it is spatially approximate to the location where the ophthalmic artery crosses the optic nerve. Our aim was to determine whether the ophthalmic artery-optic nerve crosspoint anatomically approximates the inferomedial muscular trunk in a cadaver study and can be appreciated on imaging of known posteromedial orbital lesions. MATERIALS AND METHODS: Dissection was performed on 17 fresh-frozen cadaver orbits to assess the relationship between the inferomedial muscular trunk and ophthalmic artery-optic nerve crosspoint. Retrospective review of imaging in 9 patients with posteromedial orbital lesions assessed posteromedial orbital compartment characteristics and the ability to locate the ophthalmic artery-optic nerve crosspoint. RESULTS: In our cadaver study, the mean distance between the ophthalmic artery-optic nerve crosspoint and the inferomedial muscular trunk was 1.21 ± 0.64 mm. Retrospectively, the ophthalmic artery-optic nerve crosspoint was identifiable in 9/9 patients, whereas the inferomedial muscular trunk was not identifiable in any patient. Total or partial effacement of the posteromedial intraconal fat triangle was observed in 9/9 patients. CONCLUSIONS: This study of neurovascular relationships within the posteromedial orbit demonstrates that the ophthalmic artery-optic nerve crosspoint closely approximates the inferomedial muscular trunk and can be seen in patients with posteromedial orbital lesions. Posteromedial intraconal fat effacement may help to localize these lesions. These findings may facilitate multidisciplinary communication and help predict lesion resectability and patient outcomes.


Eye Diseases/diagnostic imaging , Ophthalmic Artery/anatomy & histology , Ophthalmic Artery/diagnostic imaging , Optic Nerve/anatomy & histology , Optic Nerve/diagnostic imaging , Adult , Cadaver , Eye Diseases/surgery , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neuroendoscopy/methods , Neuroimaging/methods , Ophthalmic Artery/surgery , Optic Nerve/surgery , Orbit/anatomy & histology , Orbit/diagnostic imaging , Orbit/pathology , Retrospective Studies , Tomography, X-Ray Computed/methods
4.
PLoS One ; 15(7): e0236690, 2020.
Article En | MEDLINE | ID: mdl-32735598

A new species of Parotocinclus from the upper Rio Paraguaçu, Bahia, Brazil, is described. The new species is distinguished from all congeners by its unique color pattern, with irregular dark blotches resulting in a somewhat marble-spotted pattern on head and trunk of most specimens and dorsum of head with a conspicuous V-shaped light mark from tip of snout to nares. The new species is also distinguished from congeners by having the lower lip elongated posteriorly and reaching or surpassing the anterior margin of cleithrum on the pectoral girdle, the canal cheek plate on the ventral surface of the head reduced and with a slightly concave margin, and abdomen covered by small embedded platelets, without contact with each other and not arranged in a line between the pectoral-fin axilla and pelvic-fin origin. The presence of a thick and rough skin in the interradial membrane of pelvic fin exclusively in the females of P. nandae is reported by the first time to occurs in Siluriformes.


Catfishes/anatomy & histology , Pigmentation , Animals , Brazil , Catfishes/classification , Ecosystem , Female , Geography , Male , Sex Characteristics
5.
Brain Res ; 1741: 146887, 2020 08 15.
Article En | MEDLINE | ID: mdl-32422128

From a baby's cry to a piece of music, we perceive emotions from our auditory environment every day. Many theories bring forward the concept of common neural substrates for the perception of vocal and musical emotions. It has been proposed that, for us to perceive emotions, music recruits emotional circuits that evolved for the processing of biologically relevant vocalizations (e.g., screams, laughs). Although some studies have found similarities between voice and instrumental music in terms of acoustic cues and neural correlates, little is known about their processing timecourse. To further understand how vocal and instrumental emotional sounds are perceived, we used EEG to compare the neural processing timecourse of both stimuli type expressed with a varying degree of complexity (vocal/musical affect bursts and emotion-embedded speech/music). Vocal stimuli in general, as well as musical/vocal bursts, were associated with a more concise sensory trace at initial stages of analysis (smaller N1), although vocal bursts had shorter latencies than the musical ones. As for the P2 - vocal affect bursts and Emotion-Embedded Musical stimuli were associated with earlier P2s. These results support the idea that emotional vocal stimuli are differentiated early from other sources and provide insight into the common neurobiological underpinnings of auditory emotions.


Acoustic Stimulation/methods , Auditory Perception/physiology , Emotions/physiology , Music/psychology , Reaction Time/physiology , Voice/physiology , Adult , Electroencephalography/methods , Female , Humans , Male , Time Factors , Young Adult
6.
Acta Psychiatr Scand ; 142(1): 40-51, 2020 07.
Article En | MEDLINE | ID: mdl-32339254

BACKGROUND: Impairments of social cognition are considered core features of schizophrenia and are established predictors of social functioning. However, affective aspects of social cognition including empathy have far less been studied than its cognitive dimensions. The role of empathy in the development of schizophrenia remains largely elusive. METHODS: Emotional and cognitive empathy were investigated in large sample of 120 individuals at Clinical High Risk of Psychosis (CHR-P) and compared with 50 patients with schizophrenia and 50 healthy controls. A behavioral empathy assessment, the Multifaceted Empathy Test, was implemented, and associations of empathy with cognition, social functioning, and symptoms were determined. RESULTS: Our findings demonstrated significant reductions of emotional empathy in individuals at CHR-P, while cognitive empathy appeared intact. Only individuals with schizophrenia showed significantly reduced scores of cognitive empathy compared to healthy controls and individuals at CHR-P. Individuals at CHR-P were characterized by significantly lower scores of emotional empathy and unspecific arousal for both positive and negative affective valences compared to matched healthy controls and patients with schizophrenia. Results also indicated a correlation of lower scores of emotional empathy and arousal with higher scores of prodromal symptoms. CONCLUSION: Findings suggest that the tendency to 'feel with' an interaction partner is reduced in individuals at CHR-P. Altered emotional reactivity may represent an additional, early vulnerability marker, even if cognitive mentalizing is grossly unimpaired in the prodromal stage. Different mechanisms might contribute to reductions of cognitive and emotional empathy in different stages of non-affective psychotic disorders and should be further explored.


Cognition , Empathy , Psychotic Disorders/psychology , Schizophrenic Psychology , Social Cognition , Adult , Case-Control Studies , Female , Humans , Male , Prodromal Symptoms , Young Adult
7.
PLoS One ; 14(1): e0211352, 2019.
Article En | MEDLINE | ID: mdl-30689676

A redescription of Corydoras undulatus Regan, 1912 is presented. The original description of C. undulatus is very succinct, as is its diagnosis, which is based only on external morphology. Additional information in the scientific literature on this species is scarce. Specimens from the distribution area of this species were analyzed; Paraná and Paraguay river basins in Argentina, Uruguay river basin in Argentina, Brazil and Uruguay, and the Laguna dos Patos system in Brazil. Morphological analysis, principal component analysis (PCA), meristic comparison and osteological description were performed. Corydoras undulatus can be distinguished from its congeners mainly by having the following combination of characters: mesethmoid short, with anterior tip short, smaller than 50% of the entire bone length; posterior margin of the pectoral-fin spine with nearly all serrations directed towards origin of spine; pectoral-fin spine with conical serrations; and its peculiar color pattern. The analysis of the material from the different basins did not indicate relevant morphological differences, suggesting that the species presents a wide distribution in La Plata and Laguna dos Patos drainages. The shared geographic distribution between these two systems is also present in other fish species. The current work presents data about the type locality, taxonomy, osteology, distribution and ontogenetic variation of color pattern in C. undulatus. Comments on the identity of a very similar congener, Corydoras latus, will also be provided.


Catfishes/anatomy & histology , Animals , Argentina , Body Size , Bone and Bones/anatomy & histology , Brazil , Catfishes/physiology , Principal Component Analysis , Sex Characteristics , Skull/anatomy & histology , Uruguay
8.
Zootaxa ; 4521(4): 584-592, 2018 Nov 15.
Article En | MEDLINE | ID: mdl-30486146

Parotocinclus yaka is described as a new species of hypoptopomatine cascudinho from tributaries of the Rio Tiquié, tributary to the Rio Uaupés, upper Rio Negro drainage, Amazon basin, Amazonas State, Brazil. The new species is distinguished from its congeners in northeastern and southeastern Brazil by having the cheek canal plate elongated posteriorly on the ventral surface of the head and in contact with the cleithrum. Parotocinclus yaka is diagnosed from the Parotocinclus species of the Amazon, Orinoco and Guianas watersheds by having a conspicuous dark spots smaller than the pupil diameter distributed dorsally and laterally on the head; it is also differentiated from P. polyochrus (Casiquiare, Venezuela), P. longirostris (Rio Amazonas, Brazil), and P. eppleyi (Río Orinoco) by the absence of a Y-shaped light mark dorsally on the head. In addition, the absence of premaxillary and dentary accessory teeth and the presence of a Y-shaped spot on the snout distinguish the new species from P. collinsae (Essequibo River, Guyana), P. halbothi (Rio Trombetas, Brazil and Marowijne River, Suriname) and P. variola (Río Amazonas, Colombia). Parotocinclus yaka also differs from P. amazonensis (lower Amazon basin), P. aripuanensis (lower Amazon basin), P. britskii (Guyana, Suriname, eastern Venezuela, and Amapá State, Brazil), and P. dani (Rio Tapajós basin), by having more numerous oral teeth. The new species described herein is part of the group of small cascudinhos usually associated with marginal or submerged vegetation and submerged logs, of moderate current and clear transparency, found in conserved habitats in streams of the Amazon, Orinoco and Guianas rivers.


Catfishes , Animals , Brazil , Colombia , Guyana , Suriname , Venezuela
9.
Ann Pharm Fr ; 76(6): 489-498, 2018 Nov.
Article Fr | MEDLINE | ID: mdl-30196933

Medication adherence can be defined as the link between "what the patient implements" and "what the patient and his doctor have decided together after negotiating without constrains". This definition should be put into perspective with the chronology of the disease and the way the patient experiences it. Counselling actions should always be adapted to the situation and negotiated with the patient, all along the process of care. This article proposes a model for this process and offers options pour tailored counselling. Key elements for pharmacist's practice are: simplify the prescription; communicate with the patient according to his stage of acceptation of the disease; get adequate training for motivational interviewing.


Medication Adherence , Patient Compliance , Patients , Communication , Counseling , Humans , Pharmacists
10.
Hear Res ; 370: 272-282, 2018 12.
Article En | MEDLINE | ID: mdl-30181063

Cochlear implants can successfully restore hearing in profoundly deaf individuals and enable speech comprehension. However, the acoustic signal provided is severely degraded and, as a result, many important acoustic cues for perceiving emotion in voices and music are unavailable. The deficit of cochlear implant users in auditory emotion processing has been clearly established. Yet, the extent to which this deficit and the specific cues that remain available to cochlear implant users are unknown due to several confounding factors. Here we assessed the recognition of the most basic forms of auditory emotion and aimed to identify which acoustic cues are most relevant to recognize emotions through cochlear implants. To do so, we used stimuli that allowed vocal and musical auditory emotions to be comparatively assessed while controlling for confounding factors. These stimuli were used to evaluate emotion perception in cochlear implant users (Experiment 1) and to investigate emotion perception in natural versus cochlear implant hearing in the same participants with a validated cochlear implant simulation approach (Experiment 2). Our results showed that vocal and musical fear was not accurately recognized by cochlear implant users. Interestingly, both experiments found that timbral acoustic cues (energy and roughness) correlate with participant ratings for both vocal and musical emotion bursts in the cochlear implant simulation condition. This suggests that specific attention should be given to these cues in the design of cochlear implant processors and rehabilitation protocols (especially energy, and roughness). For instance, music-based interventions focused on timbre could improve emotion perception and regulation, and thus improve social functioning, in children with cochlear implants during development.


Auditory Perception , Cochlear Implantation/instrumentation , Cochlear Implants , Cues , Emotions , Music , Persons With Hearing Impairments/rehabilitation , Voice Quality , Acoustic Stimulation , Adult , Electric Stimulation , Female , Humans , Judgment , Male , Middle Aged , Persons With Hearing Impairments/psychology , Young Adult
11.
Sci Rep ; 7(1): 8113, 2017 08 14.
Article En | MEDLINE | ID: mdl-28808334

We evaluated the effect of different forms of singing on cardiorespiratory physiology, and we aimed at disentangling the role of breathing from that of vocal production. Cardiorespiratory recordings were obtained from 20 healthy adults at rest and during: a) singing of familiar slow songs as in the standard form of Western culture; b) improvised vocalization of free vowel sounds, known as toning. To disentangle the role of breathing from that of vocal production, we compared the vocal conditions with matched breathing-only conditions. Toning significantly improved heart rate variability, ventilatory efficiency and slowed respiration to almost exactly six breaths per minute (p < 0.001), a pattern that is known to optimize cardiovascular function and that coincides with the period of endogenous circulatory rhythms. Singing songs also positively impacted cardiorespiratory function, although to a lesser extent. The breathing pattern imposed upon participants in the absence of vocal production was sufficient to generate the physiological benefits. The effects of toning are similar to what has been previously described as a result of engaging in formal breathing exercises. Toning and singing may offer an engaging and cost effective tool to trigger beneficial respiratory patterns and the related cardiovascular benefits.


Cardiovascular System/physiopathology , Heart Rate/physiology , Respiratory Rate/physiology , Singing/physiology , Voice/physiology , Adult , Breathing Exercises/methods , Female , Humans , Male , Music , Respiration , Young Adult
12.
B-ENT ; 13(1 Suppl 27): 57-60, 2017.
Article En | MEDLINE | ID: mdl-29557564

Plunging ranula with prestyloid parapharyngeal space, masticator space, and parotid gland extension. INTRODUCTION: Ranulas develop from mucous extravasation secondary to sublingual gland duct obstruction or trauma. Plunging ranula usually dive into the submandibular space. METHODS: This is the first reported case of a plunging ranula with direct extension to the prestyloid parapharyngeal space, masticator space, and parotid gland with avoidance of the submandibular space. RESULTS: The patient presented with a tender parotid mass, of which the differential is broad, including parotitis, parotid malignancy, metastatic malignancy, lymphoma, as well as other infectious etiologies. When an intraoral component is not identified, other differential considerations would be thyroglossal duct cyst, branchial cleft cyst, parathyroid cyst, cervical thymic cyst, dermoid cyst, cystic hygroma, or benign teratoma. CONCLUSION: The case is unique due to ranula extension into multiple spaces. For optimal treatment, the sublingual gland along with its tract and contents needs to completely removed.


Ranula/pathology , Aged , Humans , Male , Parotid Diseases/etiology , Pharynx , Ranula/complications , Ranula/diagnostic imaging , Ranula/therapy
13.
Mol Ecol Resour ; 17(5): 1037-1053, 2017 Sep.
Article En | MEDLINE | ID: mdl-27863033

We present a DNA barcoding study on the insect order Orthoptera that was generated in collaboration between four barcoding projects in three countries, viz. Barcoding Fauna Bavarica (Germany), German Barcode of Life, Austrian Barcode of Life and Swiss Barcode of Life. Our data set includes 748 COI sequences from 127 of the 162 taxa (78.4%) recorded in the three countries involved. Ninety-three of these 122 species (76.2%, including all Ensifera) can be reliably identified using DNA barcodes. The remaining 26 caeliferan species (families Acrididae and Tetrigidae) form ten clusters that share barcodes among up to five species, in three cases even across different genera, and in six cases even sharing individual barcodes. We discuss incomplete lineage sorting and hybridization as most likely causes of this phenomenon, as the species concerned are phylogenetically young and hybridization has been previously observed. We also highlight the problem of nuclear mitochondrial pseudogenes (numts), a known problem in the barcoding of orthopteran species, and the possibility of Wolbachia infections. Finally, we discuss the possible taxonomic implications of our barcoding results and point out future research directions.


DNA Barcoding, Taxonomic , Orthoptera/classification , Orthoptera/genetics , Animals , Austria , DNA, Bacterial/genetics , Electron Transport Complex IV/genetics , Germany , International Cooperation , Switzerland , Wolbachia/genetics
14.
Clin Microbiol Infect ; 23(3): 179-187, 2017 Mar.
Article En | MEDLINE | ID: mdl-27793737

OBJECTIVES: In Norway, initial treatment of febrile neutropenia (FN) has traditionally been benzylpenicillin plus an aminoglycoside. Internationally, FN is often treated with a broad-spectrum ß-lactam antibiotic. We aimed to compare these two regimens in a prospective, randomized, trial in patients with lymphoma or leukaemia with an expected period of neutropenia ≥7 days, and a suspected bacterial infection. METHODS: Adult neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection, were randomized for treatment with benzylpenicillin plus an aminoglycoside or meropenem. The primary endpoint was clinical success, defined as no modification of antibiotics and clinical stability 72 h after randomization. RESULTS: Among 322 randomized patients, 297 proved evaluable for analyses. Fifty-nine per cent (95% CI 51%-66%), (87/148) of the patients given benzylpenicillin plus an aminoglycoside were clinically stable, and had no antibiotic modifications 72 h after randomization, compared with 82% (95% CI 75%-87%), (122/149) of the patients given meropenem (p <0.001). When the antibiotic therapy was stopped, 24% (95% CI 18%-32%), (36/148) of the patients given benzylpenicillin plus an aminoglycoside, compared with 52% (95% CI 44%-60%), (78/149) of the patients given meropenem, had no modifications of their regimens (p <0.001). In the benzylpenicillin plus an aminoglycoside arm, the all-cause fatality within 30 days of randomization was 3.4% (95% CI 1.2%-7.9%), (5/148) of the patients, compared with 0% (95% CI 0.0%-3.0%), (0/149) of the patients in the meropenem arm (p 0.03). CONCLUSION: Clinical success was more common in FN patients randomized to meropenem compared with the patients randomized to benzylpenicillin plus an aminoglycoside. The all-cause fatality was higher among the patients given benzylpenicillin plus an aminoglycoside.


Aminoglycosides/administration & dosage , Anti-Bacterial Agents/administration & dosage , Bacterial Infections/drug therapy , Leukemia/complications , Lymphoma/complications , Penicillin G/administration & dosage , Thienamycins/administration & dosage , Adolescent , Adult , Aged , Female , Humans , Male , Meropenem , Middle Aged , Mortality , Neutropenia/complications , Norway , Prospective Studies , Treatment Outcome , Young Adult
16.
Neotrop. ichthyol ; 15(4): e170079, 2017. tab, graf
Article En | LILACS, VETINDEX | ID: biblio-895114

The discovery of three new taxa of Hypoptotopomatini with ambiguous generic assignment prompted a reanalysis of the phylogenetic relationships of the tribe. The analysis focused on a data matrix of 56 terminals and 107 morphological characters comprising the three new taxa, most species of Hypoptopoma and Otocinclus, and all other species of the tribe. The 162 maximally parsimonious trees of 382 steps, consistency index of 0.41, and retention index of 0.83 were then summarized in a strict consensus tree. The results confirm the monophyly of the Hypoptopomatini, recover four genera as monophyletic (Acestridium, Hypoptopoma, Niobichthys, and Otocinclus), revealed Hypoptopoma and Oxyropsis to be non-monophyletic; and revealed two new genera within Hypoptopomatini. Additionally, Otocinclus was found to be sister to a group with all remaining genera of the tribe; Acestridium and Niobichthys were found to be sister to each other and that clade sister to a group formed by ((Leptotocinclus + Hypoptopoma [part]) + (Nannoxyropsis (Oxyropsis + Hypoptopoma [part]))). Based on this framework, changes to the classification and the taxonomy of the Hypoptopomatini are suggested and the new taxa are described.(AU)


A descoberta de três novos táxons pertencentes à Hypoptopomatini com designações genéricas incertas, levaram a uma nova análise das relações filogenéticas da tribo. A análise focou em uma matriz de dados formada por 56 terminais e 107 caracteres morfológicos incluindo os três novos táxons, a maioria das espécies de Hypoptopoma e Otocinclus, e todas as demais espécies da tribo. As 162 árvores maximamente parcimoniosas com 382 passos, índice de consistência 0.41 e índice de retenção 0.83 foram sumarizadas em um consenso estrito. O resultado obtido corrobora o monofiletismo de Hypoptopomatini, recupera quatro gêneros como grupos monofiléticos (Acestridium, Hypoptopoma, Niobichthys, e Otocinclus), aponta Hypoptopoma e Oxyropsis como grupos não-monofiléticos e revela dois novos gêneros pertencentes à Hypoptopomatini. Adicionalmente, Otocinclus foi encontrado como sendo grupo-irmão de um clado formado por todos os demais gêneros da tribo e Acestridium e Niobichthys formam um grupo-irmão mais relacionado a um clado formado por dois grupos monofiléticos ((Leptotocinclus + Hypoptopoma [parte]) + (Nannoxyropsis (Oxyropsis + Hypoptopoma [parte]))). Com base neste cenário, sugere-se mudanças na classificação e na taxonomia de Hypoptopomatini e os novos táxons são descritos.(AU)


Animals , Catfishes/classification , Catfishes/genetics
17.
Sci Rep ; 6: 24032, 2016 Apr 06.
Article En | MEDLINE | ID: mdl-27049119

Proteasome-catalyzed peptide splicing represents an additional catalytic activity of proteasomes contributing to the pool of MHC-class I-presented epitopes. We here biochemically and functionally characterized a new melanoma gp100 derived spliced epitope. We demonstrate that the gp100(mel)47-52/40-42 antigenic peptide is generated in vitro and in cellulo by a not yet described proteasomal condensation reaction. gp100(mel)47-52/40-42 generation is enhanced in the presence of the ß5i/LMP7 proteasome-subunit and elicits a peptide-specific CD8(+) T cell response. Importantly, we demonstrate that different gp100(mel)-derived spliced epitopes are generated and presented to CD8(+) T cells with efficacies comparable to non-spliced canonical tumor epitopes and that gp100(mel)-derived spliced epitopes trigger activation of CD8(+) T cells found in peripheral blood of half of the melanoma patients tested. Our data suggest that both transpeptidation and condensation reactions contribute to the frequent generation of spliced epitopes also in vivo and that their immune relevance may be comparable to non-spliced epitopes.


Alternative Splicing , Epitopes/chemistry , Proteasome Endopeptidase Complex/metabolism , gp100 Melanoma Antigen/chemistry , Algorithms , Antigen Presentation/immunology , Antigens/chemistry , Antigens, Neoplasm/immunology , CD8-Positive T-Lymphocytes/cytology , Case-Control Studies , Catalysis , Cell Line, Tumor , Epitopes, T-Lymphocyte/immunology , HeLa Cells , Humans , Interferon-gamma/metabolism , Melanocytes/cytology , Melanoma/metabolism , Peptides/chemistry , Probability , Proteasome Endopeptidase Complex/chemistry
18.
Diabetes Obes Metab ; 18(5): 508-18, 2016 May.
Article En | MEDLINE | ID: mdl-26863991

AIMS: To investigate the anorectic effect of L-arginine (L-Arg) in rodents. METHODS: We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. RESULTS: Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. CONCLUSIONS: L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity.


Appetite Depressants/therapeutic use , Arginine/therapeutic use , Dietary Supplements , Gastrointestinal Agents/therapeutic use , Glucagon-Like Peptide 1/agonists , Obesity/diet therapy , Peptide YY/agonists , Animals , Appetite Depressants/administration & dosage , Appetite Depressants/adverse effects , Appetite Depressants/pharmacology , Arginine/administration & dosage , Arginine/adverse effects , Cells, Cultured , Dietary Supplements/adverse effects , Energy Intake/drug effects , Energy Metabolism/drug effects , Gastrointestinal Agents/administration & dosage , Gastrointestinal Agents/adverse effects , Gastrointestinal Agents/pharmacology , Glucagon-Like Peptide 1/blood , Glucagon-Like Peptide 1/metabolism , In Vitro Techniques , Injections, Intraperitoneal , Injections, Intraventricular , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Mice, Inbred C57BL , Mice, Knockout , Obesity/drug therapy , Obesity/metabolism , Obesity/pathology , Peptide YY/blood , Peptide YY/metabolism , Random Allocation , Rats, Wistar , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Weight Loss/drug effects
19.
Oncogene ; 35(8): 965-76, 2016 Feb 25.
Article En | MEDLINE | ID: mdl-25961918

Rad18 functions at the cross-roads of three different DNA damage response (DDR) pathways involved in protecting stressed replication forks: homologous recombination repair, DNA inter-strand cross-link repair and DNA damage tolerance. Although Rad18 serves to facilitate replication of damaged genomes by promoting translesion synthesis (TLS), this comes at a cost of potentially error-prone lesion bypass. In contrast, loss of Rad18-dependent TLS potentiates the collapse of stalled forks and leads to incomplete genome replication. Given the pivotal nature with which Rad18 governs the fine balance between replication fidelity and genome stability, Rad18 levels and activity have a major impact on genomic integrity. Here, we identify the de-ubiquitylating enzyme USP7 as a critical regulator of Rad18 protein levels. Loss of USP7 destabilizes Rad18 and compromises UV-induced PCNA mono-ubiquitylation and Pol η recruitment to stalled replication forks. USP7-depleted cells also fail to elongate nascent daughter strand DNA following UV irradiation and show reduced DNA damage tolerance. We demonstrate that USP7 associates with Rad18 directly via a consensus USP7-binding motif and can disassemble Rad18-dependent poly-ubiquitin chains both in vitro and in vivo. Taken together, these observations identify USP7 as a novel component of the cellular DDR involved in preserving the genome stability.


DNA Damage , DNA Repair , DNA-Binding Proteins/metabolism , Ubiquitin Thiolesterase/metabolism , Ubiquitin-Protein Ligases/metabolism , Amino Acid Motifs , Cell Line , HeLa Cells , Humans , Protein Binding , Protein Stability , Ubiquitin/metabolism , Ubiquitin-Specific Peptidase 7
20.
Eur Arch Psychiatry Clin Neurosci ; 266(4): 337-47, 2016 Jun.
Article En | MEDLINE | ID: mdl-25900468

Under certain conditions, coercive interventions in psychotic patients can help to regain insight and alleviate symptoms, but can also traumatize subjects. This study explored attitudes towards psychiatric coercive interventions in healthy individuals and persons suffering from schizophrenia, schizoaffective or bipolar disorder. The impact of personal history of coercive treatment on preferences concerning clinical management of patients unable to consent was investigated. Six case vignettes depicting scenarios of ethical dilemmas and demanding decisions in favour of or against coercive interventions were presented to 60 healthy volunteers and 90 patients. Structured interviews focusing on experienced coercion were performed in conjunction with the Coercion Experience Scale and the Admission Experience Survey. Symptom severity, psychosocial functioning and insight into illness were assessed as influencing variables. Student's t tests compared patients' and controls' judgments, followed by regression analyses to define the predictive value of symptoms and measures of coercion on judgments regarding the total patient sample and patients with experience of fixation. Patients and non-psychiatric controls showed no significant difference in their attitudes towards involuntary admission and forced medication. Conversely, patients more than controls significantly disapproved of mechanical restraint. Subjective experience of coercive interventions played an important role for the justification of treatment against an individual's "natural will". Factors influencing judgments on coercion were overall functioning and personal experience of treatment effectiveness and fairness. Qualitative and quantitative aspects of perceived coercion, in addition to insight into illness, predicted judgments of previously fixated patients. Results underline the importance of the quality of practical implementation and care, if coercive interventions cannot be avoided.


Coercion , Hospitals, Psychiatric , Mental Disorders/psychology , Mental Disorders/therapy , Restraint, Physical/methods , Restraint, Physical/psychology , Adolescent , Adult , Female , Healthy Volunteers/psychology , Humans , Judgment , Male , Mental Disorders/classification , Middle Aged , Predictive Value of Tests , Psychiatric Status Rating Scales , Psychotherapy/methods , Surveys and Questionnaires , Young Adult
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