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1.
Curr Opin Plant Biol ; 52: 97-105, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31542698

RESUMO

Many decisions made during plant development depend on the placement of the cytokinetic wall. Cytokinesis involves the biogenesis of the cell plate that progresses centrifugally and until the fusion of the cell plate with the parental cell wall. The phragmoplast facilitates the growth of the cell plate and directs it's insertion at the cell cortex by a mechanism known as phragmoplast guidance. Communication between the phragmoplast and its destination, the cortical division zone, however, is not well understood. The preprophase band predicts the site of cell plate fusion, seemingly controlling the site of the cortical division zone establishment, but recent results suggest the role of this cytoskeletal array to be rather subtle. This is indirectly supported by certain types of phragmoplast-driven cell division in mosses and algae, which lack preprophase bands. In this review article, we summarize recent insight concerning phragmoplast expansion and guidance.

2.
Nervenarzt ; 2019 Sep 19.
Artigo em Alemão | MEDLINE | ID: mdl-31538211

RESUMO

Patients with severe mental illnesses who are unable to give consent often need a rapid diagnosis and treatment but due to the psychiatric symptoms they often reject such measures. In the routine practice, the question arises to what extent the patient's expressed will should dictate the treatment steps and whether a decision against the patient's will is medically reasonable, ethically justifiable or even demanded and legally permissible. Autoimmune encephalitides, such as N­methyl-D-aspartate receptor (NMDAR) encephalitis, have recently become important differential diagnoses due to their relative frequency, manifold symptoms and good treatability, as the underlying autoantibodies frequently cause organic psychoses. Using a complex case of a patient with NMDAR encephalitis, which was confirmed in the course of treatment, this article discusses the ethical and legal issues that are relevant in practice, from initial invasive diagnostics to involuntary confinement and compulsory treatment. The article discusses how physicians can respect the autonomy of such patients in the best way and how they can identify and resolve potential contradictions between the free will and the expressed will. Various convictions of physicians about autonomy and coercive treatment are discussed on the basis of the legal situation. Finally, it is discussed how the indications for a short compulsory treatment can be justified before the court of protection on the grounds of an analogy of autoimmune encephalitis to other severe brain diseases.

3.
J Neurooncol ; 145(1): 85-95, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31456143

RESUMO

PURPOSES: Brain metastases (BM) are a frequent complication in small cell lung cancer (SCLC), resulting in a reduced survival prognosis. Precise prognostic assessment is an important foundation for treatment decisions and clinical trial planning. METHODS: Patients with newly diagnosed SCLC BM were identified from the Vienna Brain Metastasis Registry and evaluated concerning prognostic factors. RESULTS: 489 patients (male 62.2%, female 37.8%; median age 61 years) were included. Neurological symptoms were present in 297/489 (60.7%) patients. A- to oligosymptomatic patients (5 vs. 9 months, p = 0.030) as well as patients with synchronous diagnosis of BM and primary tumor (5 vs. 9 months, p = 0.008) presented with improved overall survival (OS) prognosis. RPA (HR 1.66; 95% CI 1.44-1.91; p < 0.001), GPA (HR 1.65; p < 0.001), DS-GPA (HR 1.60; p < 0.001) and LabBM score (HR 1.69; p < 0.001) were statistically significantly associated with OS. In multivariate analysis, DS-GPA (HR 1.59; p < 0.001), neurological deficits (HR 1.26; p = 0.021) and LabBM score (HR 1.57; p < 0.001) presented with statistical independent association with OS. CONCLUSION: A- to oligosymptomatic BM as well as synchronous diagnosis of SCLC and BM were associated with improved OS. Established prognostic scores could be validated in this large SCLC BM real-life cohort.

4.
Int J Mol Sci ; 20(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466291

RESUMO

Kinesin-12 family members are characterized by an N-terminal motor domain and the extensive presence of coiled-coil domains. Animal orthologs display microtubule plus-end directed motility, bundling of parallel and antiparallel microtubules, plus-end stabilization, and they play a crucial role in spindle assembly. In plants, kinesin-12 members mediate a number of developmental processes including male gametophyte, embryo, seedling, and seed development. At the cellular level, they participate in critical events during cell division. Several kinesin-12 members localize to the phragmoplast midzone, interact with isoforms of the conserved microtubule cross-linker MICROTUBULE-ASSOCIATED PROTEIN 65 (MAP65) family, and are required for phragmoplast stability and expansion, as well as for proper cell plate development. Throughout cell division, a subset of kinesin-12 reside, in addition or exclusively, at the cortical division zone and mediate the accurate guidance of the phragmoplast. This review aims to summarize the current knowledge on kinesin-12 in plants and shed some light onto the heterogeneous localization and domain architecture, which potentially conceals functional diversification.

5.
Sci Rep ; 9(1): 9139, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235852

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically.

6.
Prax Kinderpsychol Kinderpsychiatr ; 68(4): 271-285, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-31044681

RESUMO

Participation and Information in Child and Youth Psychiatry Participation is part of children's legal rights - even in psychiatric treatment. However, former studies show that most children have barely been informed about their treatment and that their opinion has not been taken into account in any decision making process. Nowadays there is an increased awareness about involving children in the decision making process and in informing them about treatment. This subject has also gathered more importance through legal actions changed in favor of the children. We have investigated to what extend children in in-patient treatment in the child and adolescent psychiatry feel informed about and included in decisions concerning their treatment. N = 114 children of the age between 12-18 years have been asked via a written survey. Results show that more than half of the young people feel that they do have the possibility to take part in decision-making. Only a third of the participants felt sufficiently informed before and during their hospital stay.


Assuntos
Psiquiatria do Adolescente , Psiquiatria Infantil , Tomada de Decisões , Participação do Paciente/psicologia , Adolescente , Criança , Humanos , Consentimento Informado por Menores/ética , Consentimento Informado por Menores/psicologia , Consentimento Informado por Menores/estatística & dados numéricos , Tempo de Internação , Participação do Paciente/estatística & dados numéricos , Inquéritos e Questionários
7.
Curr Opin Cell Biol ; 60: 9-18, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30999231

RESUMO

The plant microtubules form unique arrays using acentrosomal microtubule nucleation pathways, yet utilizing evolutionary conserved centrosomal proteins. In cytokinesis, a multi-component cytoskeletal apparatus, the phragmoplast mediates the biosynthesis of the new cell plate by dynamic centrifugal expansion, a process that demands exquisite coordination of microtubule turnover and endomembrane trafficking. At the same time, the phragmoplast is guided to meet with the parental wall at a cortical site that is predefined before mitotic entry and transiently marked by the preprophase band of microtubules. The cortical division zone maintains positional information of the selected division plane for the entire duration of cell division and for the guidance of the phragmoplast during cytokinesis. Its establishment is an essential requirement for normal plant organogenesis, due to the confinement of cells by rigid cell walls.

8.
Ann N Y Acad Sci ; 1447(1): 135-143, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30941784

RESUMO

The hairpin ribozyme is a small, naturally occurring RNA that catalyzes the reversible cleavage of RNA substrates. Among the small endonucleolytic ribozymes, the hairpin ribozyme possesses the unique feature of the internal equilibrium between cleavage and ligation being shifted toward ligation. This allows control of the reaction outcome by structural design: fragments that are strongly bound to the ribozyme are preferentially ligated, whereas substrates that easily dissociate upon cleavage, such that they are not available for religation, are preferentially cleaved. We have made use of this characteristic feature in engineering a number of hairpin ribozyme variants by programmed conformational design that carry out cascades of cleavage and ligation reactions, and as a result mediate more complex RNA processing reactions. Here, we review our work on the engineering of hairpin ribozyme variants for RNA recombination and regular and back-splicing, and discuss the relevance of such activities in early life.

9.
Br J Haematol ; 186(2): 311-320, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30968400

RESUMO

Prior studies indicate that neutrophil extracellular traps (NETs) are associated with arterial thromboembolism (ATE) and mortality. We investigated the association between NET formation biomarkers (citrullinated histone H3 [H3Cit], cell-free DNA [cfDNA], and nucleosomes) and the risk of ATE and all-cause mortality in patients with cancer. In this prospective cohort study, H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients with newly diagnosed cancer or progressive disease after remission were followed for 2 years for ATE and death. Nine-hundred and fifty-seven patients were included. The subdistribution hazard ratios for ATE of H3Cit, cfDNA and nucleosomes were 1·0 per 100 ng/ml increase (95% confidence interval [95% CI]: 0·7-1·4, P = 0·949), 1·0 per 100 ng/ml (0·9-1·2, P = 0·494) increase and 1·1 per 1-unit increase (1·0-1·2, P = 0·233), respectively. Three-hundred and seventy-eight (39·5%) patients died. The hazard ratio (HR) for mortality of H3Cit and cfDNA per 100 ng/ml increase was 1·1 (1·0-1·1, P < 0·001) and 1·1 (1·0-1·1, P < 0·001), respectively. The HR for mortality of nucleosome levels per 1-unit increase was 1·0 (1·0-1·1, P = 0·233). H3Cit, cfDNA and nucleosome levels were not associated with the risk of ATE in patients with cancer. Elevated H3Cit and cfDNA levels were associated with higher mortality in patients with cancer.

10.
J Ment Health ; 28(3): 304-311, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30761924

RESUMO

BACKGROUND: The burden of mental illness (MI) is exacerbated when adolescents with MI are confronted with stigma and social exclusion. Adolescents face the difficult decision whether or not to disclose their MI. Focus groups (FGs) were conducted with parents of adolescents with MI as well as with teachers, mental health professionals (MHPs) and adolescents without MI. AIM: To collect information from relevant stakeholders on secrecy versus disclosure of MI among adolescents. METHODS: Thirteen FG sessions with 87 participants were recorded, transcribed and analyzed using qualitative content analysis to identify major themes. RESULTS: Selective disclosure and social media as a potential way of disclosure emerged as dominant themes. Negative aspects of disclosure on social media were discussed. Stigma and labeling were seen as disadvantages of disclosure. Social support was perceived as one advantage of disclosure. Distinctive features of adolescence, such as self-discovery, appeared as specific problems. Parents, teachers, MHPs and adolescents without MI were considered important for disclosure. Participants discussed how to help adolescents with their dilemma between disclosure and secrecy. CONCLUSIONS: The findings suggest that disclosure decisions are personal and influenced by the individual's environment. Implications for interventions that aim to support adolescents with MI in this regard are discussed.

11.
Annu Rev Plant Biol ; 70: 239-267, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-30795703

RESUMO

Plant cells divide their cytoplasmic content by forming a new membrane compartment, the cell plate, via a rerouting of the secretory pathway toward the division plane aided by a dynamic cytoskeletal apparatus known as the phragmoplast. The phragmoplast expands centrifugally and directs the cell plate to the preselected division site at the plasma membrane to fuse with the parental wall. The division site is transiently decorated by the cytoskeletal preprophase band in preprophase and prophase, whereas a number of proteins discovered over the last decade reside continuously at the division site and provide a lasting spatial reference for phragmoplast guidance. Recent studies of membrane fusion at the cell plate have revealed the contribution of functionally conserved eukaryotic proteins to distinct stages of cell plate biogenesis and emphasize the coupling of cell plate formation with phragmoplast expansion. Together with novel findings concerning preprophase band function and the setup of the division site, cytokinesis and its spatial control remain an open-ended field with outstanding and challenging questions to resolve.

12.
J Ment Health ; 28(3): 296-303, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30596301

RESUMO

BACKGROUND: Many adolescents with mental illness (MI) struggle with the decision whether to disclose their condition. They may decide to keep their MI secret, whether due to fear of public stigma or due to self-stigma and shame. Secrecy may protect against discrimination, but has often negative long-term consequences such as social isolation. AIM: To explore personal views of adolescents with MI on secrecy and disclosure of their MI. METHOD: Six focus groups consisting of 39 adolescents with MI were recorded, transcribed, and analyzed by qualitative content analysis to identify major themes deductively and inductively. RESULTS: Participants described MI as a stigmatized condition and stressed both the benefits and risks of secrecy. Disadvantages included fear of stigma and loss of friendships, benefits included emotional support and relief. Adolescents underlined the importance of individual disclosure decisions (DDs). The majority preferred selective disclosure. Additionally, the role of other adolescents with and without MI was emphasized. CONCLUSIONS: DDs are individual and depend on social factors since stigma and fear of discrimination remain significant concerns for adolescents with MI. Implications for future interventions to support adolescents with MI are discussed.

13.
Biochim Biophys Acta Mol Basis Dis ; 1865(9): 2083-2093, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30557699

RESUMO

Mutations in the X chromosomal tRNA 2'­O­methyltransferase FTSJ1 cause intellectual disability (ID). Although the gene is ubiquitously expressed affected individuals present no consistent clinical features beyond ID. In order to study the pathological mechanism involved in the aetiology of FTSJ1 deficiency-related cognitive impairment, we generated and characterized an Ftsj1 deficient mouse line based on the gene trapped stem cell line RRD143. Apart from an impaired learning capacity these mice presented with several statistically significantly altered features related to behaviour, pain sensing, bone and energy metabolism, the immune and the hormone system as well as gene expression. These findings show that Ftsj1 deficiency in mammals is not phenotypically restricted to the brain but affects various organ systems. Re-examination of ID patients with FTSJ1 mutations from two previously reported families showed that several features observed in the mouse model were recapitulated in some of the patients. Though the clinical spectrum related to Ftsj1 deficiency in mouse and man is variable, we suggest that an increased pain threshold may be more common in patients with FTSJ1 deficiency. Our findings demonstrate novel roles for Ftsj1 in maintaining proper cellular and tissue functions in a mammalian organism.

14.
Org Biomol Chem ; 16(45): 8824-8830, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30411775

RESUMO

The use of templates able to control the assembly and disassembly of supramolecular biopolymers is an attractive approach with applications ranging from engineering new biopolymers to the modulation of complex biological systems. Self-assembled nucleic acid-based systems hold thus substantive potential for the construction of well-defined and stimuli-responsive molecular architectures. We report here for the first time the synthesis of a 5'-boronoribonucleotidic phosphoramidite building block, its incorporation at the 5' extremities of RNA sequences, and its ability to generate boronate internucleosidic linkages by RNA- and DNA-templated ligation. Moreover, melting denaturation studies also revealed that 5'-boronic acid ended RNA sequences are able to promote the formation of RNA loops in the presence of RNA templating partners. Molecular-dynamics (MD) simulations were used to model the structural parameters governing these processes.

15.
Curr Protoc Nucleic Acid Chem ; 75(1): e60, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30375750

RESUMO

We have developed two methods, in solution and on solid phase, that give easy access to trinucleotide phosphoramidites capable of undergoing coupling reactions by the solid-phase phosphoramidite approach. The solution protocol is characterized by application of 5'-O-dimethoxytrityl (DMT) and 3'-O-tert-butyldimethylsilyl (TBDMS) as a pair of orthogonal protecting groups and 2-cyanoethyl (CE) for protection of the phosphate. Starting with suitably functionalized monomers, synthesis proceeds in the 3'- to 5'-direction, delivering the fully protected trinucleotide. The 3'-O-protecting group is cleaved followed by phosphitylation of the free 3'-OH group. The solid-phase protocol is based on standard phosphoramidite chemistry in conjunction with a dithiomethyl linkage connecting the 3'-starting nucleoside to the polymer. The disulfide bridge can be cleaved under neutral conditions for release of the trinucleotide from the support preserving all other protecting groups. © 2018 by John Wiley & Sons, Inc.

16.
J Environ Manage ; 231: 429-438, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30368153

RESUMO

Seabirds select suitable habitats at sea, but these habitats may be strongly impacted by marine spatial planning, including the construction of offshore wind farms (OWFs) and the associated ship traffic. Loons (Gavia spp.) are particularly vulnerable to anthropogenic activities and are also of high conservation status, making them particularly relevant to marine planning processes. We investigated the effects of OWF construction and ship traffic on Loon distributions in the German North Sea on a large spatial scale, using a 'before-after' control impact analysis approach and a long-term data set. Many OWFs were built in or close to core areas of Loon distributions. Loons showed significant shifts in their distribution in the 'after' period and subsequently aggregated between two OWF clusters, indicating the remaining suitable habitat. The decrease in Loon abundance became significant as far as about 16 km from the closest OWF. Ship traffic also had a significant negative impact on Loons, indicating that OWFs deterred Loons through the combined effect of ship traffic and the wind turbines themselves. This study provides the first analysis of the extensive effects of OWFs and ships on Loons on a large spatial scale. The results provide an essential baseline for future marine spatial planning processes in the German North Sea and elsewhere.

17.
Acta Neurochir (Wien) ; 160(12): 2501-2507, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30357485

RESUMO

BACKGROUND: Comments made by readers in response to news articles about current events can provide profound insights into public understanding of and perspectives on those events. Here, in follow up to a paper published last year in this journal, we examined reader comments to articles in newspapers and magazines about neurosurgical interventions for treating psychiatric illness. METHOD: We conducted a thematic analysis of these comments (N = 662 coded units of data) posted in response to 115 newspaper and magazine articles from four countries (Canada, USA, Germany, and Spain) between 2006 and 2017. The comments were coded using an iteratively refined coding scheme that was structured around four a priori categories based on results from the parent study and two new categories that emerged. RESULTS: We found many references to historical psychosurgery and mostly negative and pessimistic comments about ablative neurosurgical interventions. Comments to deep brain stimulation were more positive, and comments to optogenetics most controversial. We also found many expressions of distrust of medical professionals in the context of interventions on the brain and concerns about social and individual control. CONCLUSIONS: Overall, results suggest there is still much work to be done to raise public awareness about re-emerging and new neurosurgical interventions. Balanced discussion is needed if these approaches are to find a place in health care for psychiatric disorders.

18.
Org Biomol Chem ; 16(41): 7663-7673, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30283974

RESUMO

Charge transfer across double stranded DNA was observed for the first time about 20 years ago, and ever since it has been the subject of a large number of studies. RNA has been hardly investigated in this regard, which not least is due to the lack of suitably functionalized ribonucleotide building blocks to serve as electron sources upon incorporation into oligoribonucleotides. We have synthesized two uridine derivatives carrying pyrene or dimethylaminopyrene linked to C5 of the nucleobase. The key to successful synthesis was the adaptation of Suzuki-Miyaura conditions to the coupling of the pyrene moiety with the ribonucleoside. Final decoration of the pyrenylated nucleosides with standard 5'-O- and 2'-O-protecting groups and subsequent 3'-O-phosphitylation delivered the building blocks for incorporation into RNA. Spectroscopic analysis of the two pyrenylated uridines and of the accordingly modified oligonucleotides showed that in particular the dimethyaminopyrene functionalized nucleoside is a promising candidate as an electron source for RNA charge transport studies.

19.
Fortschr Neurol Psychiatr ; 86(8): 485-492, 2018 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-30125919

RESUMO

The UN Convention for the Rights of People with Disabilities (CRPD) has influenced the jurisdiction and legislation on psychiatry in Germany. It played a role in several landmark decisions of the Federal Constitutional Court and of the Federal Supreme Court, which again initiated changes of the guardianship law and of different federal mental health laws. Furthermore, the CRPD has triggered an intensive discussion within psychiatry, which has led to a more critical and cautious use of coercive measures.However, the interpretation of the CRPD is controversial. The UN Committee on the Rights of Persons with Disabilities has published in 2014 a "General Comment on Article 12 of the UN Convention". Therein, the Committee interprets the CRPD in a way that differs questionably from former international statements about human rights and from former WHO recommendations. Particularly, the Committee demands the complete abolition of substitute decisions by legal guardians and the complete elimination of confinement and of coercive measures.The German government does not accept the Committee's interpretation of the CRPD. The Federal Constitutional Court has declared that the Committee's statements are not legally binding under public international law, neither for national nor for international courts. Furthermore, the Federal Constitutional Court has criticized the Committee's position. Particularly, it has declared that the CRPD does not imply a total ban of substitute decisions and coercive measures. The Federal Constitutional Court rather acknowledges the state's duty to protect especially those people who cannot decide freely and who are in a helpless situation because of illness or disability. The Court has declared that the state must not abandon these people to their fate.The Federal Constitutional Court has interpreted the CRPD by balancing different fundamental rights and by differentiating between the free and the natural will. In contrast, the Committee has absolutized a naïvely understood right for self-determination.

20.
Biophys J ; 115(2): 375-385, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30021112

RESUMO

Plant development and morphology relies on the accurate insertion of new cell walls during cytokinesis. However, how a plant cell correctly orients a new wall is poorly understood. Two kinesin class-12 members, phragmoplast orienting kinesin 1 (POK1) and POK2, are involved in the process, but how these molecular machines work is not known. Here, we used in vivo and single-molecule in vitro measurements to determine how Arabidopsis thaliana POK2 motors function mechanically. We found that POK2 is a very weak, on average plus-end-directed, moderately fast kinesin. Interestingly, POK2 switches between processive and diffusive modes characterized by an exclusive-state mean-squared-displacement analysis. Our results support a model that POK motors push against peripheral microtubules of the phragmoplast for its guidance. This pushing model may mechanically explain the conspicuous narrowing of the division site. Together, our findings provide mechanical insight into how active motors accurately position new cell walls in plants.

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