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1.
Cell Rep ; 42(11): 113372, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37938971

RESUMO

Metacaspases are ancestral homologs of caspases that can either promote cell death or confer cytoprotection. Furthermore, yeast (Saccharomyces cerevisiae) metacaspase Mca1 possesses dual biochemical activity: proteolytic activity causing cell death and cytoprotective, co-chaperone-like activity retarding replicative aging. The molecular mechanism favoring one activity of Mca1 over another remains elusive. Here, we show that this mechanism involves calmodulin binding to the N-terminal pro-domain of Mca1, which prevents its proteolytic activation and promotes co-chaperone-like activity, thus switching from pro-cell death to anti-aging function. The longevity-promoting effect of Mca1 requires the Hsp40 co-chaperone Sis1, which is necessary for Mca1 recruitment to protein aggregates and their clearance. In contrast, proteolytically active Mca1 cleaves Sis1 both in vitro and in vivo, further clarifying molecular mechanism behind a dual role of Mca1 as a cell-death protease versus gerontogene.


Assuntos
Peptídeo Hidrolases , Proteínas de Saccharomyces cerevisiae , Peptídeo Hidrolases/metabolismo , Calmodulina/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Caspases/metabolismo , Saccharomyces cerevisiae/metabolismo , Chaperonas Moleculares/metabolismo
2.
Plant Cell ; 35(9): 3325-3344, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37401663

RESUMO

Stress granules (SGs) are highly conserved cytoplasmic condensates that assemble in response to stress and contribute to maintaining protein homeostasis. These membraneless organelles are dynamic, disassembling once the stress is no longer present. Persistence of SGs due to mutations or chronic stress has been often related to age-dependent protein-misfolding diseases in animals. Here, we find that the metacaspase MC1 is dynamically recruited into SGs upon proteotoxic stress in Arabidopsis (Arabidopsis thaliana). Two predicted disordered regions, the prodomain and the 360 loop, mediate MC1 recruitment to and release from SGs. Importantly, we show that MC1 has the capacity to clear toxic protein aggregates in vivo and in vitro, acting as a disaggregase. Finally, we demonstrate that overexpressing MC1 delays senescence and this phenotype is dependent on the presence of the 360 loop and an intact catalytic domain. Together, our data indicate that MC1 regulates senescence through its recruitment into SGs and this function could potentially be linked to its remarkable protein aggregate-clearing activity.


Assuntos
Arabidopsis , Animais , Arabidopsis/genética , Arabidopsis/metabolismo , Agregados Proteicos , Grânulos de Estresse , Grânulos Citoplasmáticos/metabolismo , Estresse Fisiológico
3.
Int J Mol Sci ; 24(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37108757

RESUMO

Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an insufficient understanding of the conditions and particularly of lipohypertrophy. In our study, we performed histological and molecular analysis in anatomically-, BMI- and gender-matched samples of lipedema, lipohypertrophy and secondary lymphedema versus healthy control patients. Hereby, we found a significantly increased epidermal thickness only in patients with lipedema and secondary lymphedema, while significant adipocyte hypertrophy was identified in both lipedema and lipohypertrophy. Interestingly, the assessment of lymphatic vessel morphology showed significantly decreased total area coverage in lipohypertrophy versus the other conditions, while VEGF-D expression was significantly decreased across all conditions. The analysis of junctional genes often associated with permeability indicated a distinct and higher expression only in secondary lymphedema. Finally, the evaluation of the immune cell infiltrate verified the increased CD4+ cell and macrophage infiltration in lymphedema and lipedema respectively, without depicting a distinct immune cell profile in lipohypertrophy. Our study describes the distinct histological and molecular characteristics of lipohypertrophy, clearly distinguishing it from its two most important differential diagnoses.


Assuntos
Lipedema , Lipodistrofia , Vasos Linfáticos , Linfedema , Humanos , Lipedema/genética , Lipedema/metabolismo , Linfedema/genética , Vasos Linfáticos/metabolismo , Lipodistrofia/diagnóstico , Diagnóstico Diferencial
4.
J Plast Surg Hand Surg ; 57(1-6): 1-6, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34591727

RESUMO

OBJECTIVES: The challenge in the operative therapy for enlargement of the male breast is to deal with the skin excess. Shape and scars are the major parameters after which patients assess their operative result. Therefore, we assessed the satisfaction rate among patients undergoing subcutaneous mastectomy at our institution with special regard to scar tissue formation and the postoperative appearance of the chest wall in dependence of the surgical approach (periarolar versus inframammary fold). METHODS: The study includes n = 36 male patients who underwent subcutaneous mastectomy at AGAPLESION Markus Hospital Frankfurt/Main. Patient's satisfaction dependent with the appearance of the chest wall and scar formation was evaluated by a modified BREAST Q® questionnaire plus two male-based additional questions. RESULTS: There is no statistically significant difference in satisfaction with the operative result depending on the pattern of incision (periareolar versus submammary periareolar; 81.9% versus 75.5%) with the operative result. Evaluation of additional questions of the modified BREAST Q® questionnaire showed that 86% of the patients (n = 31) would rather have more scars and a flatter chest wall. A BMI >25 kg/m2 is accompanied by a higher risk for complications (p = 0.04). CONCLUSIONS: Periareolar incision is still the method of choice, if promising an aesthetic appealing result. When reaching its limits though, we showed that a flat and male-shaped appearance of the chest wall is priority for the patients and should therefore be for the surgeon as well.


Assuntos
Neoplasias da Mama , Ginecomastia , Mamoplastia , Humanos , Masculino , Cicatriz/etiologia , Cicatriz/cirurgia , Ginecomastia/cirurgia , Neoplasias da Mama/cirurgia , Mastectomia , Estudos Retrospectivos , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Mamoplastia/efeitos adversos , Mamoplastia/métodos
5.
J Biol Chem ; 298(11): 102476, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36096201

RESUMO

The accumulation of misfolded proteins is a hallmark of aging and many neurodegenerative diseases, making it important to understand how the cellular machinery recognizes and processes such proteins. A key question in this respect is whether misfolded proteins are handled in a similar way regardless of their genetic origin. To approach this question, we compared how three different misfolded proteins, guk1-7, gus1-3, and pro3-1, are handled by the cell. We show that all three are nontoxic, even though highly overexpressed, highlighting their usefulness in analyzing the cellular response to misfolding in the absence of severe stress. We found significant differences between the aggregation and disaggregation behavior of the misfolded proteins. Specifically, gus1-3 formed some aggregates that did not efficiently recruit the protein disaggregase Hsp104 and did not colocalize with the other misfolded reporter proteins. Strikingly, while all three misfolded proteins generally coaggregated and colocalized to specific sites in the cell, disaggregation was notably different; the rate of aggregate clearance of pro3-1 was faster than that of the other misfolded proteins, and its clearance rate was not hindered when pro3-1 colocalized with a slowly resolved misfolded protein. Finally, we observed using super-resolution light microscopy as well as immunogold labeling EM in which both showed an even distribution of the different misfolded proteins within an inclusion, suggesting that misfolding characteristics and remodeling, rather than spatial compartmentalization, allows for differential clearance of these misfolding reporters residing in the same inclusion. Taken together, our results highlight how properties of misfolded proteins can significantly affect processing.


Assuntos
Doenças Neurodegenerativas , Proteínas de Saccharomyces cerevisiae , Humanos , Agregados Proteicos , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Doenças Neurodegenerativas/metabolismo , Dobramento de Proteína , Proteínas de Choque Térmico/metabolismo , Guanilato Quinases/metabolismo
6.
Animals (Basel) ; 12(18)2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36139229

RESUMO

Mammals are constantly exposed to exogenous and endogenous influences that affect their behaviour and daily activity. Light and temperature, as well as anthropogenic factors such as husbandry routines, visitors, and feeding schedules are potential influences on animals in zoological gardens. In order to investigate the effects of some of these factors on animal behaviour, observational studies based on the analyses of activity budgets can be used. In this study, the daily and nightly activity budgets of six lions (Panthera leo) and five cheetahs (Acinonyx jubatus) from four EAZA institutions were investigated. Focused on the influencing factor light and feeding, we analysed these activity budgets descriptively. Behaviour was recorded and analysed during the winter months over an observation period of 14 days and 14 nights using infrared-sensitive cameras. Our results show that lions and cheetahs exhibit activity peaks at crepuscular and feeding times, regardless of husbandry. Thus, lions in captivity shift nocturnal behaviour familiar from the wild to crepuscular and diurnal times. In cheetahs, in contrast, captive and wild individuals show similar 24 h behavioural rhythms. The resting behaviour of both species is more pronounced at night, with cheetahs having a shorter overall sleep duration than lions. This study describes the results of the examined animals and is not predictive. Nevertheless, the results of this study make an important contribution to gaining knowledge about possible factors influencing the behaviour of lions and cheetahs in zoos and offer implications that could be useful for improving husbandry and management.

7.
Front Immunol ; 13: 1004609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36605202

RESUMO

Lipedema is a chronic and progressive adipose tissue disorder, characterized by the painful and disproportionate increase of the subcutaneous fat in the lower and/or upper extremities. While distinct immune cell infiltration is a known hallmark of the disease, its role in the onset and development of lipedema remains unclear. To analyze the macrophage composition and involved signaling pathways, anatomically matched lipedema and control tissue samples were collected intra-operatively from gender- and BMI-matched patients, and the Stromal Vascular Fraction (SVF) was used for Cytometry by Time-of-Flight (CyTOF) and RNA sequencing. The phenotypic characterization of the immune component of lipedema versus control SVF using CyTOF revealed significantly increased numbers of CD163 macrophages. To gain further insight into this macrophage composition and molecular pathways, RNA sequencing of isolated CD11b+ cells was performed. The analysis suggested a significant modification of distinct gene ontology clusters in lipedema, including cytokine-mediated signaling activity, interleukin-1 receptor activity, extracellular matrix organization, and regulation of androgen receptor signaling. As distinct macrophage populations are known to affect adipose tissue differentiation and metabolism, we evaluated the effect of M2 to M1 macrophage polarization in lipedema using the selective PI3Kγ inhibitor IPI-549. Surprisingly, the differentiation of adipose tissue-derived stem cells with conditioned medium from IPI-549 treated SVF resulted in a significant decreased accumulation of lipids in lipedema versus control SVF. In conclusion, our results indicate that CD163+ macrophages are a critical component in lipedema and re-polarization of lipedema macrophages can normalize the differentiation of adipose-derived stem cells in vitro evaluated by the cellular lipid accumulation. These data open a new chapter in understanding lipedema pathophysiology and may indicate potential treatment options.


Assuntos
Lipedema , Humanos , Lipedema/genética , Lipedema/metabolismo , Transcriptoma , Adipócitos/metabolismo , Diferenciação Celular , Macrófagos
8.
Anim Microbiome ; 3(1): 77, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736528

RESUMO

BACKGROUND: Through the rapid development in DNA sequencing methods and tools, microbiome studies on a various number of species were performed during the last decade. This advance makes it possible to analyze hundreds of samples from different species at the same time in order to obtain a general overview of the microbiota. However, there is still uncertainty on the variability of the microbiota of different animal orders and on whether certain bacteria within a species are subject to greater fluctuations than others. This is largely due to the fact that the analysis in most extensive comparative studies is based on only a few samples per species or per study site. In our study, we aim to close this knowledge gap by analyzing multiple individual samples per species including two carnivore suborders Canoidea and Feloidea as well as the orders of herbivore Perissodactyla and Artiodactyla held in different zoos. To assess microbial diversity, 621 fecal samples from 31 species were characterized by sequencing the V3-V4 region of the 16S rRNA gene using Illumina MiSeq. RESULTS: We found significant differences in the consistency of microbiota composition and in fecal microbial diversity between carnivore and herbivore species. Whereas the microbiota of Carnivora is highly variable and inconsistent within and between species, Perissodactyla and Ruminantia show fewer differences across species boundaries. Furthermore, low-abundance bacterial families show higher fluctuations in the fecal microbiota than high-abundance ones. CONCLUSIONS: Our data suggest that microbial diversity is significantly higher in herbivores than in carnivores, whereas the microbiota in carnivores, unlike in herbivores, varies widely even within species. This high variability has methodological implications and underlines the need to analyze a minimum amount of about 10 samples per species. In our study, we found considerable differences in the occurrence of different bacterial families when looking at just three and six samples. However, from a sample number of 10 onwards, these within-species fluctuations balanced out in most cases and led to constant and more reliable results.

9.
Cell Rep ; 35(13): 109328, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34192536

RESUMO

In this paper, we show that the essential Hsp90 co-chaperone Sgt1 is a member of a general protein quality control network that links folding and degradation through its participation in the degradation of misfolded proteins both in the cytosol and the endoplasmic reticulum (ER). Sgt1-dependent protein degradation acts in a parallel pathway to the ubiquitin ligase (E3) and ubiquitin chain elongase (E4), Hul5, and overproduction of Hul5 partly suppresses defects in cells with reduced Sgt1 activity. Upon proteostatic stress, Sgt1 accumulates transiently, in an Hsp90- and proteasome-dependent manner, with quality control sites (Q-bodies) of both yeast and human cells that co-localize with Vps13, a protein that creates organelle contact sites. Misfolding disease proteins, such as synphilin-1 involved in Parkinson's disease, are also sequestered to these compartments and require Sgt1 for their clearance.


Assuntos
Proteínas de Choque Térmico HSP90/metabolismo , Dobramento de Proteína , Proteólise , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Citosol/metabolismo , Retículo Endoplasmático/metabolismo , Genes Fúngicos , Células HeLa , Humanos , Mutação/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Agregados Proteicos , Ligação Proteica , Saccharomyces cerevisiae/genética
10.
Zoo Biol ; 40(3): 171-181, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33666286

RESUMO

Upon a drastic decline of the giraffe population in the wild, conservation efforts and therefore the role of zoos have become more important than ever. With their unique opportunities, zoos provide excellent conditions to study animal behavior, expanding the knowledge about the giraffe's behavior repertoire and their ability to adapt. This study therefore examined the nocturnal behavior of 63 giraffe living in 13 different EAZA zoos across Germany and the Netherlands. Giraffe were observed and videos recorded via infrared sensitive cameras during the winter seasons 2015-2018. The observation period spanned nightly from 17:00 to 7:00. Thus, 198 nights, with a total of 2772 h were recorded and analyzed. Linear mixed models were then used to assess potential biological and environmental factors influencing behavior during the dark phase. Results show that individual variables such as age, subspecies and motherhood determined nocturnal activity and sleep behavior most. Among the variables studied, husbandry conditions and environmental factors complying with EAZA standards had no influence on the giraffe's nocturnal behavior. By combining nocturnal activity analyses and an assessment of potential influencing factors, our findings present a holistic approach to a better understanding of captive giraffe behavior and allow for management implications.


Assuntos
Criação de Animais Domésticos/métodos , Girafas/fisiologia , Abrigo para Animais , Animais , Animais de Zoológico , Comportamento Animal , Ritmo Circadiano , Feminino , Girafas/classificação , Masculino , Sono , Especificidade da Espécie
11.
J Environ Radioact ; 229-230: 106544, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33556790

RESUMO

Uranium (U) is a naturally occurring metal; its environmental levels can be increased due to processes in the nuclear industry and fertilizer production. The transfer of U in the food chain from plants is associated with deleterious chemical and radiation effects. To date, limited information is available about U toxicity on plant physiology. This study investigates the responses of metal-accumulating plants to different concentrations of U. The plants Noccaea caerulescens and Noccaea goesingense are known as metal hyperaccumulators and therefore could serve as candidates for the phytoremediation of radioactive hotspots; Plantago major is a widely used pharmaceutical plant that pioneers polluted grounds and therefore should not contain high concentrations of toxic elements. The experimental plants were grown hydroponically at U concentrations between 1 µM and 10 mM. The content of U and essential elements was analyzed in roots and leaves by ICP-MS. The amount of accumulated U was influenced by its concentration in the hydroponics. Roots contained most of the metal, whereas less was transported up to the leaves, with the exception of N. goesingense in a medium concentration of U. U also influenced the nutrient profile of the plants. We localized the U in plant tissues using EDX in the SEM. U was evenly distributed in roots and leaves of Noccaea species, with one exception in the roots of N. goesingense, where the central cylinder contained more U than the cortex. The toxicity of U was assessed by measuring growth and photosynthetic parameters. While root biomass of N. caerulescens was not affected by U, root biomass of N. goesingense decreased significantly at high U concentrations of 0.1 and 10 mM and root biomass of P. major decreased at 10 mM U. Dry weight of leaves was decreased at different U concentrations in the three plant species; a promotive effect was observed in N. caerulescens at lowest concentration offered. Chlorophyll a fluorescence was not affected or negatively affected by U in both Noccaea species, whereas in Plantago also positive effects were observed. Our results show that the impact of U on Plantago and Noccaea relates to its external concentration and to the plant species. When growing in contaminated areas, P. major should not be used for medicinal purpose. Noccaea species and P. major could immobilize U in their rhizosphere in hotspots contaminated by U, and they could extract limited amounts of U into their leaves.


Assuntos
Brassicaceae , Plantago , Monitoramento de Radiação , Poluentes do Solo , Urânio , Clorofila A , Raízes de Plantas , Urânio/toxicidade
12.
PLoS Genet ; 17(1): e1008951, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33428620

RESUMO

70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and accelerates replicative aging. In our efforts to identify which Hsp70 activities are most important for longevity assurance, we systematically investigated the capacity of Ssa4 to carry out the different activities performed by Ssa1/2 by overproducing Ssa4 in cells lacking these Hsp70 chaperones. We found that Ssa4, when overproduced in cells lacking Ssa1/2, rescued growth, mitigated aggregate formation, restored spatial deposition of aggregates into protein inclusions, and promoted protein degradation. In contrast, Ssa4 overproduction in the Hsp70 deficient cells failed to restore the recruitment of the disaggregase Hsp104 to misfolded/aggregated proteins, to fully restore clearance of protein aggregates, and to bring back the formation of the nucleolus-associated aggregation compartment. Exchanging the nucleotide-binding domain of Ssa4 with that of Ssa1 suppressed this 'defect' of Ssa4. Interestingly, Ssa4 overproduction extended the short lifespan of ssa1Δ ssa2Δ mutant cells to a lifespan comparable to, or even longer than, wild type cells, demonstrating that Hsp104-dependent aggregate clearance is not a prerequisite for longevity assurance in yeast.


Assuntos
Adenosina Trifosfatases/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Longevidade/genética , Proteínas de Saccharomyces cerevisiae/genética , Citosol/metabolismo , Chaperonas Moleculares/genética , Proteínas Mutantes/genética , Mutação/genética , Dobramento de Proteína , Saccharomyces cerevisiae/genética
13.
Urology ; 141: 154-161, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32283166

RESUMO

OBJECTIVE: To evaluate the outcome of a single-center series of penile reconstruction using the radial free forearm flap in rare indications. MATERIALS AND METHODS: From April 1993 until September 2016, 23 nontranssexual patients underwent phallic reconstruction by the use of a neuromicrovascular free radial forearm flap in our clinic. Patient-specific characteristics, surgical techniques, complications, and outcomes were retrospectively evaluated and interpreted. RESULTS: The indications for surgery were: disorders of sex development (34.8%), reconstruction after oncologic surgery (34.8%), automutilation (8.7%), iatrogenic (8.7%), microphallus (8.7%), and 1 case of priapism (4.3%). Two patients (8.7%) had a total flap necrosis and 2 patients (8.7%) had a partial flap necrosis; 3 out of these 4 patients were heavy smokers. Urinary fistulae and strictures were frequent but were successfully managed by urologists in all cases. There was no statistically significant correlation between smoking, comorbidities, number of venous anastomoses, and complications. CONCLUSION: In departments experienced in microsurgery, the goals of penile reconstruction could also be achieved in patients with rare indications by the use of the neuromicrovascular free radial forearm flap. Despite the high rate of postoperative complications, penile reconstruction with the free radial forearm flap yields satisfying results. An intensive cooperation between the plastic-reconstructive team and the urological team is a prerequisite to achieve the best surgical result.


Assuntos
Doenças do Pênis/etiologia , Pênis/cirurgia , Retalho Perfurante , Procedimentos de Cirurgia Plástica/métodos , Estruturas Criadas Cirurgicamente , Fístula Urinária/etiologia , Adulto , Antebraço/cirurgia , Humanos , Masculino , Microcirurgia/efeitos adversos , Microcirurgia/métodos , Pessoa de Meia-Idade , Necrose/etiologia , Doenças do Pênis/cirurgia , Pênis/anormalidades , Pênis/lesões , Retalho Perfurante/efeitos adversos , Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/inervação , Retalho Perfurante/patologia , Artéria Radial , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Estruturas Criadas Cirurgicamente/efeitos adversos , Uretra/cirurgia , Adulto Jovem
14.
Ecol Evol ; 10(6): 2917-2927, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32211165

RESUMO

This study presents the first findings on nocturnal behavior patterns of wild Angolan giraffe. We characterized their nocturnal behavior and analyzed the influence of ecological factors such as group size, season, and habitat use. Giraffe were observed using night vision systems and thermal imaging cameras on Okapuka Ranch, Namibia. A total of 77 giraffe were observed during 24 nights over two distinct periods-July-August 2016 (dry season) and February-March 2017 (wet season). Photoperiod had a marked influence on their activity and moving behavior. At dusk, giraffe reduced the time spent moving and increasingly lay down and slept at the onset of darkness. Body postures that likely correspond to rapid eye movement (REM) sleep posture (RSP) were observed 15.8 ± 18.3 min after giraffe sat down. Season had a significant effect with longer RSP phases during the dry season (dry: 155.2 ± 191.1 s, n = 79; wet: 85.8 ± 94.9 s, n = 73). Further analyses of the influence of social behavior patterns did not show an effect of group size on RSP lengths. When a group of giraffe spent time at a specific resting site, several individuals were alert (vigilant) while other group members sat down or took up RSP. Simultaneous RSP events within a group were rarely observed. Resting sites were characterized by single trees or sparse bushes on open areas allowing for good visibility in a relatively sheltered location.

15.
J Sex Med ; 17(5): 1012-1024, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32201146

RESUMO

BACKGROUND: Constructing a sensitive phallus is a key objective in sex affirmation surgery, but still there is a major lack of evidence in outcome analysis of postoperative sensibility of the newly constructed body part. AIM: To evaluate the innervation and sensibility of a forearm free-flap neophallus with nerve coaptation by a broad-spectrum follow-up. METHODS: The phallic sensibility of 20 transgender individuals who underwent phalloplasty with a free radial forearm flap was evaluated by a standardized multimodal approach, examining 5 main sensory modalities. Measurements were performed in defined areas at the phallus and at the unoperated forearm as a control area. Additionally, all patients were asked to complete a questionnaire about their subjective quality of life and ability to orgasm. OUTCOME: This study evaluated the following parameters: perception of pressure (Semmes-Weinstein monofilaments) and vibration (C64 Hz tuning fork), static two-point discrimination, sharp-blunt and hot-cold discrimination at the phallus and the forearm, sum score of calculated life satisfaction, and ability to orgasm. RESULTS: Most of the patients (n = 14) were able to perceive 2 or more sensory modalities tested at the newly constructed phallus. 2 patients did not develop any sensibility. Interestingly, the median values for vibration perception were similar for the phallus and the unoperated forearm. Pressure sensibility was present at the phallus, but less than at the forearm. Moreover, sharp-blunt sensibility was present in 11 patients. In contrast, clear cold-warm discrimination could not be achieved, although the majority of patients detected the cold stimulus. A two-point discrimination of up to 23 mm could not be detected in either body part. 15 patients experienced orgasms without difficulty after 23 months (n = 20 after 54 months). CLINICAL IMPLICATIONS: We observed successful recovery of sensibility at the phalli for the majority of patients, including the preservation of orgasm. STRENGTHS & LIMITATIONS: Our institution is one of the few centers regularly performing phalloplasties in transgender patients, especially preferring the technique of Gottlieb and Levine. This study contributes to the few studies that perform sensory testing at the phallus and is unique in its kind in that it uses a multimodal approach. A limitation of this study is the limited number of cases and the limited validity of vibratory testing. CONCLUSION: Confirming a promising tactile sensibility after phalloplasty with a neurovascular radial forearm flap, the next step would be to identify whether this reinnervation effectively develops due to nerve coaptation or spontaneous sprouting. Küenzlen L, Nasim S, van Neerven S, et al. Multimodal Evaluation of Functional Nerve Regeneration in Transgender Individuals After Phalloplasty With a Free Radial Forearm Flap. J Sex Med 2020;17:1012-1024.


Assuntos
Cirurgia de Readequação Sexual , Pessoas Transgênero , Antebraço/cirurgia , Humanos , Masculino , Regeneração Nervosa , Pênis/cirurgia , Qualidade de Vida
16.
Gland Surg ; 8(5): 516-526, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31741882

RESUMO

BACKGROUND: The aim of a mastopexy is to raise the breast projection, tighten the skin envelope, and place the nipples in an optimal position in projection to the inframammary fold. This procedure is often combined with prosthetic implants or an autoimplant. Given the current increasing demand for the use of autologous tissue, we evaluated mastopexies combined with either an autoimplant or prosthetic implant in terms of patient satisfaction and long-term results. METHODS: We evaluated 34 patients who underwent a mastopexy with simultaneous breast prosthesis or an autoimplant. During follow-ups we obtained standardized breast measurements, BREAST-Q score, and pre- and postoperative photographs to perform photometric measurements. RESULTS: BREAST-Q score of patients that underwent autoimplant-mastopexies revealed a higher patient satisfaction with significant differences in satisfaction with breast appearance (69±18 vs. 55±16, P=0.03) and outcome (71±18 vs. 48±26, P=0.009). Regarding breast shape, photometric evaluations presented a significantly different breast shape with higher upper pole fullness in augmentation-mastopexy patients. No statistical significance between long-term results and complication rates could be observed in either patient groups. CONCLUSIONS: The BREAST-Q score implies a higher overall long-term satisfaction in patients that received autoimplant-mastopexy with similar long-term results compared with augmentation-mastopexy. Nevertheless, individual decision-making is necessary and should be based on the degree of ptosis, existing breast volume, previous operations, and patients' preferences regarding postoperative breast shape and projection.

17.
Ecotoxicol Environ Saf ; 184: 109625, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31518824

RESUMO

Stable isotopes of cesium (Cs) and strontium (Sr) as well as their radioactive isotopes are of serious environmental concern. The pollution of the biosphere, particularly soil and water has received considerable attention for removal of these contaminants in recent years. Arabidopsis halleri (A. halleri) is a hyperaccumulator plant species able to take up large amounts of several metals into its above ground organs without showing significant signs of toxicity. Therefore, we investigated responses, metal accumulation and element distribution in roots and leaves of A. halleri after treatment with stable Cs and Sr. Plants were hydroponically grown in different concentrations of cesium sulfate (between 0.002 and 20 mM) and strontium nitrate (between 0.001 and 100 mM). Uptake of Cs and Sr into leaves was analyzed from extracts by inductively coupled plasma mass spectrometry (ICP-MS). Although internal concentration of Cs and Sr increased with rising external concentrations, the amount of accumulated metal in relation to available metal decreased. Therefore, the potential of the plant to effectively transfer metals from growth medium to leaves occurred at low and moderate concentrations, whereas after that when the concentration of metal increased further the transfer factors were decreased. A. halleri accumulated Sr more efficiently than Cs. The transfer factors were higher for Sr (up to 184) than for Cs (up to 16). The results indicate positive correlation of Cs and Sr accumulation to K and Ca transport to leaves. The toxicity of Cs and Sr was assessed by measuring photosynthetic efficiency and growth parameters. In leaves, Cs and Sr affected the chlorophyll fluorescence at their low and high concentrations. Significant reduction of plant growth (dry weight of roots and leaves) was observed at Sr concentrations >0.01 mM. Cs-treated plants exhibited only decreased length of leaves at concentrations>0.02 mM. The distribution of the elements within the different tissues of leaves and roots was investigated by using Energy Dispersive X-Ray microanalysis (EDX) with a scanning electron microscope (SEM). EDX revealed that Cs and Sr were accumulated differently in root and leaf tissues. The hydroponic experiment showed a potential for A. halleri to treat hotspots with radioactive Cs and Sr.


Assuntos
Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Césio/metabolismo , Césio/toxicidade , Nitratos/metabolismo , Nitratos/toxicidade , Estrôncio/metabolismo , Estrôncio/toxicidade , Arabidopsis/crescimento & desenvolvimento , Biodegradação Ambiental , Hidroponia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
18.
Environ Pollut ; 254(Pt B): 113084, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31473385

RESUMO

Human activities lead to increasing concentration of the stable elements cesium (Cs) and strontium (Sr) and their radioactive isotopes in the food chain, where plants play an important part. Here we investigated Plantago major under the influence of long-term exposure to stable Cs and Sr. The plants were cultivated hydroponically in different concentrations of cesium sulfate (between 0.002 and 20 mM) and strontium nitrate (between 0.001 and 100 mM). Uptake of Cs and Sr into leaves was analyzed from extracts by inductively coupled plasma mass spectrometry (ICP-MS). It was increased with increasing external Cs and Sr concentrations. However, the efficiency of Cs and Sr transfer from solution to plants was higher for low external concentrations. Highest transfer factors were 6.78 for Cs and 71.13 for Sr. Accumulation of Sr was accompanied by a slight decrease of potassium (K) and calcium (Ca) in leaves, whereas the presence of Cs in the medium affected only uptake of K. The toxic effects of Cs and Sr were estimated from photosynthetic reactions and plant growth. In leaves, Cs and Sr affected the chlorophyll fluorescence even at their low concentrations. Low and high concentrations of both ions reduced dry weight and length of roots and leaves. The distribution of the elements between the different tissues of leaves and roots was investigated using Energy Dispersive X-Ray microanalysis (EDX) with scanning electron microscope (SEM). Overall, observations suggested differential patterns in accumulating Cs and Sr within the roots and leaves. When present in higher concentrations the amount of Cs and Sr transferred from environment to plants was sufficient to affect some physiological processes. The experimental model showed a potential for P. major to study the influence of radioactive contaminants and their removal from hotspots.


Assuntos
Césio/análise , Nitratos/metabolismo , Fotossíntese , Plantago/metabolismo , Estrôncio/metabolismo , Cálcio/análise , Cálcio/metabolismo , Césio/metabolismo , Hidroponia , Nitratos/análise , Folhas de Planta/química , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Plantago/crescimento & desenvolvimento , Potássio/análise , Potássio/metabolismo , Poluentes Radioativos do Solo/análise , Poluentes Radioativos do Solo/metabolismo , Estrôncio/análise
19.
Sci Total Environ ; 653: 1458-1512, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30759584

RESUMO

Radiostrontium is released to the environment from routine and accidental discharge and acts on living organisms either from external sources or after absorption. When incorporated by plants, it enters the food chain and causes primary threat to human health and the environment. Understanding the mechanisms of plants for strontium uptake and retention is therefore essential for decision making concerning agriculture: are uptake rates low enough so that plants can serve as food? Or is radiostrontium accumulated so that plants should not be eaten but could be probably used for extracting strontium from water and soil in hot spots of pollution? The review presents a summary of studies about the origin of stable and radioactive strontium in the environment and effects coming from both internal and external exposure of plants. Mobility and availability of strontium to plant roots in soil are controlled by external factors such as chemical composition of the soil and pH, temperature and agricultural soil cultivation as well as soil biological networks built by microbial communities. Plant surfaces may receive input of strontium from deposition induced by atmospheric pollution or by acquisition from water through the whole immersed surface. Cells have entry mechanisms for strontium such as plasma membrane transporters for calcium and potassium. Part of absorbed strontium can be lost via processes discussed in this review. We give examples on strontium transfer factors for 149 plants to estimate plant absorption capacity for strontium from soil, water and air. Uptake efficiency of terrestrial and aquatic plants is deciding about their remediation potential to either remove radiostrontium by accumulation and rhizofiltration or to retain it in roots or aerial parts. Data of strontium content in soils after fallout and edible plants from long-term monitoring support the evaluation of the potential hazards posed by strontium input to the food chain.


Assuntos
Monitoramento Ambiental , Plantas/metabolismo , Isótopos de Estrôncio/análise , Estrôncio/análise , Biodegradação Ambiental , Cadeia Alimentar , Plantas/efeitos dos fármacos , Estrôncio/metabolismo , Isótopos de Estrôncio/metabolismo
20.
Sci Total Environ ; 618: 1459-1485, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29122347

RESUMO

Radiocesium in water, soil, and air represents a severe threat to human health and the environment. It either acts directly on living organisms from external sources, or it becomes incorporated through the food chain, or both. Plants are at the base of the food chain; it is therefore essential to understand the mechanisms of plants for cesium retention and uptake. In this review we summarize investigations about sources of stable and radioactive cesium in the environment and harmful effects caused by internal and external exposure of plants to radiocesium. Uptake of cesium into cells occurs through molecular mechanisms such as potassium and calcium transporters in the plasma membrane. In soil, bioavailability of cesium depends on the chemical composition of the soil and physical factors such as pH, temperature and tilling as well as on environmental factors such as soil microorganisms. Uptake of cesium occurs also from air through interception and absorption on leaves and from water through the whole submerged surface. We reviewed information about reducing cesium in the vegetation by loss processes, and we extracted transfer factors from the available literature and give an overview over the uptake capacities of 72 plants for cesium from the substratum to the biomass. Plants with high uptake potential could be used to remediate soil and water from radiocesium by accumulation and rhizofiltration. Inside plants, cesium distributes fast between the different plant organs and cells, but cesium in soil is extremely stable and remains for decades in the rhizosphere. Monitoring of contaminated soil therefore has to continue for many decades, and edible plants grown on such soil must continuously be monitored.


Assuntos
Biodegradação Ambiental , Radioisótopos de Césio/metabolismo , Monitoramento de Radiação , Poluentes Radioativos do Solo/metabolismo , Radioisótopos de Césio/análise , Rizosfera , Poluentes Radioativos do Solo/análise
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