39 research outputs found

    Neurological deficits and glycosphingolipid accumulation in saposin B deficient mice

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    Saposin B derives from the multi-functional precursor, prosaposin, and functions as an activity enhancer for several glycosphingolipid (GSL) hydrolases. Mutations in saposin B present in humans with phenotypes resembling metachromatic leukodystrophy. To gain insight into saposin B's physiological functions, a specific deficiency was created in mice by a knock-in mutation of an essential cysteine in exon 7 of the prosaposin locus. No saposin B protein was detected in the homozygotes (B−/−) mice, whereas prosaposin, and saposins A, C and D were at normal levels. B−/− mice exhibited slowly progressive neuromotor deterioration and minor head tremor by 15 months. Excess hydroxy and non-hydroxy fatty acid sulfatide levels were present in brain and kidney. Alcian blue positive (sulfatide) storage cells were found in the brain, spinal cord and kidney. Ultrastructural analyses showed lamellar inclusion material in the kidney, sciatic nerve, brain and spinal cord tissues. Lactosylceramide (LacCer) and globotriaosylceramide (TriCer) were increased in various tissues of B−/− mice supporting the in vivo role of saposin B in the degradation of these lipids. CD68 positive microglial cells and activated GFAP positive astrocytes showed a proinflammatory response in the brains of B−/− mice. These findings delineate the roles of saposin B for the in vivo degradation of several GSLs and its primary function in maintenance of CNS function. B−/− provide a useful model for understanding the contributions of this saposin to GSL metabolism and homeostasis

    Specific saposin C deficiency: CNS impairment and acid β-glucosidase effects in the mouse

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    Saposins A, B, C and D are derived from a common precursor, prosaposin (psap). The few patients with saposin C deficiency develop a Gaucher disease-like central nervous system (CNS) phenotype attributed to diminished glucosylceramide (GC) cleavage activity by acid β-glucosidase (GCase). The in vivo effects of saposin C were examined by creating mice with selective absence of saposin C (C−/−) using a knock-in point mutation (cysteine-to-proline) in exon 11 of the psap gene. In C−/− mice, prosaposin and saposins A, B and D proteins were present at near wild-type levels, but the saposin C protein was absent. By 1 year, the C−/− mice exhibited weakness of the hind limbs and progressive ataxia. Decreased neuromotor activity and impaired hippocampal long-term potentiation were evident. Foamy storage cells were observed in dorsal root ganglion and there was progressive loss of cerebellar Purkinje cells and atrophy of cerebellar granule cells. Ultrastructural analyses revealed inclusions in axonal processes in the spinal cord, sciatic nerve and brain, but no excess of multivesicular bodies. Activated microglial cells and astrocytes were present in thalamus, brain stem, cerebellum and spinal cord, indicating regional pro-inflammatory responses. No storage cells were found in visceral organs of these mice. The absence of saposin C led to moderate increases in GC and lactosylceramide (LacCer) and their deacylated analogues. These results support the view that saposin C has multiple roles in glycosphingolipid (GSL) catabolism as well as a prominent function in CNS and axonal integrity independent of its role as an optimizer/stabilizer of GCase

    Is there an association between insomnia symptoms, aggressive behavior, and suicidality in adolescents?

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    Maria Zschoche, Angelika Anita Schlarb Faculty of Psychology and Sports Science, University of Bielefeld, Bielefeld, Germany Purpose: Sleep disturbances are a common problem during adolescence. Often there is a relationship with the mental health of the affected person. The existing literature concerning the link between sleep disturbances and aggressive behavior and sleep disturbances and suicidality during adolescence shows no clear results. The present study tested a mediation model to prove the relation between sleep problems, aggressive behavior, and suicidality during adolescence. To take the link between suicidality and depression into account, the amount of depressive symptoms was included into the mediation model. Methods: A sample of 93 adolescents aged 14–18 years (30% male) was studied. A survey was conducted to interview the adolescents about their mental health, sleep-related behaviors, aggressive behavior, and suicidality. Results: Sleep problems and suicidality measures were significantly related to each other. Furthermore, aggressive behavior and suicidality showed a significant relationship. The expected link between sleep problems and aggressive behavior was not significant. For the mediation model, no significant influence of aggressive behavior on the relationship between the amount of sleep problems and suicidality was found. However, the impact of depressive symptoms on the relationship between sleep problems and suicidality was significant. Conclusion: Sleep problems and overall suicidality in adolescents are significantly connected, even after adjusting for several possible influencing factors. Aggressive behavior could not be confirmed as a mediator for the association between sleep problems and suicidality in adolescents. Further studies to examine the link between insomnia symptoms, aggressive behavior, and suicidality in adolescents are necessary. Keywords: adolescents, aggressive behavior, sleep problems, suicidality, depressio

    Nightmare's effects on daily functioning - the nightmare effects questionnaire (NEQ)

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    Schlarb A, Zschoche M, Schredl M. Nightmare's effects on daily functioning - the nightmare effects questionnaire (NEQ). In: Abstracts of the 22nd Congress of the European Sleep Research Society, 16–20 September 2014, Tallinn, Estonia. Journal of Sleep Research. Vol 23. Hoboken: Wiley Blackwell (Blackwell Publishing); 2014: 107-107

    The complexity of transitively orienting temporal graphs

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    In a temporal network with discrete time-labels on its edges, entities and information can only “flow” along sequences of edges whose time-labels are non-decreasing (resp. increasing), i.e. along temporal (resp. strict temporal) paths. Nevertheless, in the model for temporal networks of [Kempe, Kleinberg, Kumar, JCSS, 2002], the individual time-labeled edges remain undirected: an edge e = {u, v} with time-label t specifies that “u communicates with v at time t”. This is a symmetric relation between u and v, and it can be interpreted that the information can flow in either direction. In this paper we make a first attempt to understand how the direction of information flow on one edge can impact the direction of information flow on other edges. More specifically, naturally extending the classical notion of a transitive orientation in static graphs, we introduce the fundamental notion of a temporal transitive orientation and we systematically investigate its algorithmic behavior in various situations. An orientation of a temporal graph is called temporally transitive if, whenever u has a directed edge towards v with time-label t1 and v has a directed edge towards w with time-label t2 ≥ t1, then u also has a directed edge towards w with some time-label t3 ≥ t2. If we just demand that this implication holds whenever t2 > t1, the orientation is called strictly temporally transitive, as it is based on the fact that there is a strict directed temporal path from u to w. Our main result is a conceptually simple, yet technically quite involved, polynomial-time algorithm for recognizing whether a given temporal graph G is transitively orientable. In wide contrast we prove that, surprisingly, it is NP-hard to recognize whether G is strictly transitively orientable. Additionally we introduce and investigate further related problems to temporal transitivity, notably among them the temporal transitive completion problem, for which we prove both algorithmic and hardness results

    The complexity of transitively orienting temporal graphs

    Get PDF
    In a temporal network with discrete time-labels on its edges, entities and information can only “flow” along sequences of edges whose time-labels are non-decreasing (resp. increasing), i.e. along temporal (resp. strict temporal) paths. Nevertheless, in the model for temporal networks of [Kempe, Kleinberg, Kumar, JCSS, 2002], the individual time-labeled edges remain undirected: an edge e = {u, v} with time-label t specifies that “u communicates with v at time t”. This is a symmetric relation between u and v, and it can be interpreted that the information can flow in either direction. In this paper we make a first attempt to understand how the direction of information flow on one edge can impact the direction of information flow on other edges. More specifically, naturally extending the classical notion of a transitive orientation in static graphs, we introduce the fundamental notion of a temporal transitive orientation and we systematically investigate its algorithmic behavior in various situations. An orientation of a temporal graph is called temporally transitive if, whenever u has a directed edge towards v with time-label t1 and v has a directed edge towards w with time-label t2 ≥ t1, then u also has a directed edge towards w with some time-label t3 ≥ t2. If we just demand that this implication holds whenever t2 > t1, the orientation is called strictly temporally transitive, as it is based on the fact that there is a strict directed temporal path from u to w. Our main result is a conceptually simple, yet technically quite involved, polynomial-time algorithm for recognizing whether a given temporal graph G is transitively orientable. In wide contrast we prove that, surprisingly, it is NP-hard to recognize whether G is strictly transitively orientable. Additionally we introduce and investigate further related problems to temporal transitivity, notably among them the temporal transitive completion problem, for which we prove both algorithmic and hardness results

    Ocular lymphoma Precise diagnostics and classification as key for successful personalized treatment

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    Background Personalized medicine is nowadays the standard of care for patients with oncological diseases. A prime example is the lymphoma, which has substantial points of contact with ophthalmological care due to the intraocular and periocular involvement. Objective This article provides a description of the current personalized diagnostics and treatment of ocular lymphomas. Methods This article constructs a relationship between the current knowledge in the literature, guidelines and recommendations and the clinical experience with ocular lymphomas. It explains in particular the molecular and also individual personalized treatment concepts. Results The primary suspicion of lymphatic or other ocular oncological diseases is raised by an ophthalmologist based on clinical symptoms. The exact diagnostic procedure is carried out with molecular biological techniques, such as immunohistology and polymerase chain reaction analyses. A staging of the mass is indispensable and the stage classification according to the Ann Arbor criteria for a correct assignment of the lymphoma is of clinical importance. Based on these precise diagnostics an individualized choice of treatment and subsequent personalized follow-up care are carried out. During the complete process from the diagnostic procedure to treatment and aftercare, psycho-oncological support should be offered to the patient. Conclusion Personalized medicine is already actively performed in the care of ocular lymphomas. The patient is in the forefront and plays a decisive role. By considering the special features of the tumor and patient parameters, the life expectation and relapse-free interval as well as quality of life have been improved for many types of lymphoma. It must be assumed that these advantages also apply to ophthalmology

    Swelling behavior of bisensitive interpenetrating polymer networks for microfluidic applications

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    Bisensitive interpenetrating polymer network (IPN) hydrogels of temperature sensitive net-poly(Nisopropylacrylamide) and pH sensitive net-poly(acrylic acid-co-acrylamide) for microfluidic applications were prepared via a sequential synthesis using free radical polymerization. The IPN indicated a suitable reversible alteration of swelling in response to the change in pH and temperature. The adequate change of the hydrogel volume is a basic requirement for microfluidic applications. Using the introduced correction factor f, it is possible to determine the cooperative diffusion coefficient (Dcoop) of cylindrical samples at any aspect ratio. The determined cooperative diffusion coefficient allowed the evaluation of varying swelling processes of different network structures. The presence of the second sub-network of the IPN improved the swelling behaviour of the first sub-network compared to the individual networks
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